Recombivax HB Clinical Trial

TABLE OF CONTENTS
Vol ume Starting

' Page
I. Su11111a ri es l 00001
A. Brief Sumnary
B. General Sunanary
Appendix (Vaccine Lots)
II. lllTllune Affinity Vaccine 00052

A. Sunrnary
B. Synopses
c. Individual Study Sunrnaries
III. 6 2f Vaccine 1 00121

A. Test for Non1nfect1vity 1 00121
a. Synopsis
b. Individual Study Sunrnary
B. Inrnunogenicity/Safety l 00128
1. Health Care Personnel and Other l 00128
Healthy Adults
a. Sunmary
b. Appendix (Statistical Methods)
c. Synopses
d. Individual Study Sumnaries
2. Healthy Teenagers (15-20 years old) 2 00617
a. Individual Study Sumnary

b. Append1x (Statistical Methods)
3. Healthy Infants and Children z 00645
a. Sunmary
c. Synopses
d. Individual Study Sunrnartes
24691/1
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SUMMARY .FOR BASIS OF APPROVAL
Reference No. 85-053 Drug Licensed Name: Hepatitis B Vaccine

(Recombinant)
Mfr: Merck Sharp & Dobme (MSD) Drug Trade )Jame: RECOMBIVAX ffBO
Hepatitis B Vaccine (Recombinant), RECOMBIVAX HB, is a non-infectious subunit

viral vaccine derived from synthetic hepatitis B surface antigen (HBsAg)
produced in yeast cells. A plasmid containing a portion of hepatitis B virus
gene coding for HBsAg is cloned into yeast, and· the vaccine for hepatitis Bis
produced from cultures of this recombinant yeast strain.
I. INDICATIONS FOR USE:
RECOMBIVAX HB is indicated for immunization against infection caused by

all known subtypes of hepatitis B virus (HBV). The vaccine has been
shown to be effective in inducing an immune response (anti-HBs) in
initially seronegative adults and children. It has been shown to be
effective in preventing chronic hepatitis B infection among infants of
carrier mothers when used in conjunction with one dose of hepatitis B
immune globulin.
RECOMBIVAX HB will not prevent hepatitis caused by other agents such as

hepatitis A virus, non-A, non-B hepatitis viruses or other viruses known
to infect the liver.
Vaccination is recommended for those persons who are or will be at

increased risk of infection with all known subtypes of hepatitis B virus,
including persons employed in a variety of health care occupations,
patients requiring frequent and/or large volume blood transfusions or
clotting factor concentrates, residents and staff of institutions for the
mentally handicapped, intimate contacts of persons with persistent
hepatitis B antigenemia, infants born to HBsAg positive mothers, persons
at increased risk due to their sexual practices, and users of illicit
injectable drugs. Additional studies are in progress in dialysis
patients.
Studies are ongoing to determine the need and timing for revaccination.
II. DOSAGE AND ADKIRISTRATIOH:
RECOMBIVAX HB consists of hepatitis B surface antigen which is produced

in yeast cells. The isolated and purified antigen is adsorbed onto
aluminum hydroxide as an adjuvant, and thimerosal is added as a
preservative. A 1.0 ml dose of the adult fonnulation of the vaccine
2
contains 10 mcg of hepatitis B surface antigen adsorbed onto 0 . 5 mg of

aluminum hydroxide; a 0 . 5 ml dose of the pediatl"ic fonnulation contains
5 mcg of hepatitis B surface antigen adsorbed onto 0.25 mg of aluminum
hydroxide. All formulations of vaccine contain 1:20,000 thimerosal as
preservative. The vaccine has been treated with formaldehyde prior to
adsorption onto alum.
Primacy vaccination consists of three injections of vaccine, with the

second and third injections given land 6 months, respectively, after the ·
first . Adults and children above 10 years of age are given 10 mcg
(1.0 ml) of hepatitis B surface antigen per injection, while children
from birth to 10 years of age receive 5 mcg (0.5 ml) of hepatitis 8
surface antigen per injection. Infants born to HBsAg positive mothers
should receive at birth Hepatitis 8 Immune Globulin in conjunction with
the first dose of RECOMBIVAX HB in different sites . All injections are
given intramuscularly in the deltoid muscle in adults and children or in
the anterolateral thigh muscle in infants and neonates, except those
given to persons with hemophilia or similar disorders which are given
subcutaneously. Data suggest that injections given in the buttocks are
less effective in producing an immune response, perhaps since injections
in the buttocks may frequently be given into fatty tissue instead of into
muscle.
III . MANUFACTURING A.ND CONTROLS:
A. MANUFACTURING A.ND CONTROLS
The organism, Saccha romyces cerev1s1ae, strain (b)(4)

(b)(4) • which is utilized for the production of HBsAg,
contains a plasmid containing a gene for the adw subtype of HBsAg.
The culture is grown in a Yeast Extract/Soy Peptone/Dextrose (YEHD)
medium at (b)(4) The fermentations are
(b)(4)
(b)(4)
(b)(4)
3
(b)(4)
The final container is tested for sterility, general safety,

(b)(4) thimerosal, (b)(4)
aluminum (b)(4) and potency in mice (b)(4)
(b)(4)
The manufacturer submitted for evaluation samples and protocols of

five final container lots of vaccine derived from five different
bulk lots produced initially at production scale. These lots met
the release specifications listed at the time of their manufacture .
Subsequently, modifications to the release specifications have been
incorporated into the license application. These include a
(b)(4) yeast impurity specification from (b)(4)
to (b)(4) and a change in the (b)(4) specification _for the mouse
potency test from 3.0 mcg/ml to 1.5 mcg/ml . The specification
requires that (b)(4)
(b)(4) Additional lots have been submitted
for release which when tested by the manufacturer meet all of the
current relea~e specifications .
B. STABILITY STUDIES
The recoawended storage temperature of the vaccine, adsorbed onto

alum is 2-8°c. Stability of the vaccine was monitored by the
demonstration of potency in an in vivo mouse model and by (b)(4)
(b)(4) (b)(4) . of the vaccine was studied through (b)(4)
(b)(4) at 2- 8°c . and (b)(4) to 24 months at 2-s 0 c . No
significant differences in potency which would indicate a loss in
the immunizing potential of the product were obset-ved throughout the
period. Other studies are in orocess. Accelerated stability
studies at (b)(4) were carried
out . By the mouse potency assay, statistically significant
degradation was noted only at (b)(4) By (b)(4) measurable loss of
antigen occurred at temperatures (b)(4)
(b)(4)
4
The product will have an expiration dating of twenty-four months at

2-a 0 c. The package insert recommends storage at 2-a 0 c. which is
supported by the stability studies. Merck has committed to conduct
ongoing stability studies.
C. VALIDATION
The major equipment used in the manufacture and filling of the

vaccine has been validated at the Merck & Co., Inc., West Point, PA,
facilities. In addition, appropriate specifications have been
established for monitoring environmental conditions for critical·
work areas in this facility by the Environmental Control Department,
KSD. Validation analyses for product potency and purity are
performed at MSD. The test methods were found to be suitable for
control and regulatory purposes.
D. LABELING
The labeling, including the package insert, has been reviewed for
compliance with 21 CFR 610.60, 610.61, 610.62, 201.56 and 201.57 and
found satisfactory. The container label includes a warning
statement indicating .. Do Not Inject Intravenously", a caution
statement that federal law prohibits dispensing without
prescription, a statement to .. Shake Well Before Using .. , a statement
to store at 2-a 0 c. (35.6 - 46.4°F) and a warning statement ..Do
Not Freeze ... A statement to see the accompanying circular for
dosage instructions is also included.
The package insert (copy attached) contains appropriate statements

concerning product description, clinical pharmacology, indications
and use, contraindications, warnings, precautions, adverse
reactions, how supplied, dosage and administration and information
on the storage of the vaccine.
E. ESTABLISHMENT INSPECTION
A pre-license inspection of the MSD biological production facilities

in West Point, PA, was conducted Kay 12-14, 1986. Mo
objectionable practices or exceptions to the regulations were
observed.
F. ENVIRONMENTAL IMPACT ANALYSIS REPORT
An environmental assessment for the manufacture and use of

RECOMBIVAX HB was completed to address the environmental impact
considerations of 21 CFR, Part 25. The information provided for
this environmental assessment supports the finding of no significant
environmental impact. (Exhibit 2)
5
IV. PHARMACOLOGY, BIOCHEMISTRY AUD SEROLOGY:
RECOKBIVAX HB is composed of HBsAg which is the product of a plasmid

containing a portion of the hepatitis B virus gene that codes for HBsAg
and which was derived from plasma of a donor infected with hepatitis 8
viru.s , subtype adw. This plasmid has been cloned into yeast. (b)(4)
(b)(4)
Serological studies have been perfonned to evaluate the anti-HBs

antibodies raised in recipients of yeast - derived vaccine . Cross-
adsorption studies were perfonned on anti-HBs in five recipients of
yeast-derived vaccine four months post - vaccination and in six recipients
of plasma-derived vaccine three months post-vaccina~ion. In all five
samples from yeast vaccine recipients 99-100!. of the anti - HBs antibodies
were adsorbed by both yeast- deri ved and plasma-derived antigen. In the
six samples from plasma-derived vaccine recipients, 99- 100!. of the
anti-HBs antibodies were adsorbed by plasma-derived HBsAg and 87 - 991. by
yeast-derived antigen . The mean affinity constants obtained against a
synthetic cyclic peptide derived from the HBsAg sequence were 4 x 10 7
for antibodies from both plasma- derived vaccine recipients and
yeast-derived vaccine recipients.
An inhibition assay using a monoclonal antibody that had been shown to

protect chimpanzees from hepatitis B infection showed 38'1. inhibition
(10- 69~) of the monoclonal antibody by samples from 10 yeast-derived
vaccinees and 54~ inhibition (18- 991.) by samples from 10 plasma-derived
vaccinees .
Avidity constants against entire HBsAg ranged from 4 to 8 x 1010 in

six samples at 3 months post - vaccination from plasma-derived vaccinees
and l to 16 x 1010 in six samples from yeast-derived vaccinees .
Comparison of the proportions of the anti - a and anti- d components of the

anti-HBs response showed that at 7 months post- vaccination 95~ of the
anti - HBs was anti-a and 5~ anti- din 27 samples of yeast vaccine
recipients and 93~ anti- a and 7~ anti - din 8 samples from plasma-derived
vaccine recipients .
6
These serological studies show that although the antibodies induced by

yeast-derived and plasma-derived antigen are comparable, 1) yeast-derived
antigen is slightly less capable of adsorbing antibody induced by
plasma-derived antigen, 2) the antibody induced by yeast-derived antigen
is somewhat less reactive in a cross inhibition assay with a protective
monoclonal antibody and 3) the antibodies induced by yeast-derived
antigen show greater variability in their avidity constants.
V. MEDICAL:
A. GENERAL INFORMATION
Hepatitis B virus is one of several viruses (hepatitis A, hepatitis.

Band several non-A, non-B hepatitis) causing a systemic infection
with pathologic changes in the liver. It is a major cause of acute
and chronic hepatitis and cirrhosis and has been implicated in the
etiology of primary hepatocellular carcinoma worldwide. There is no
effective treatment for hepatitis B infection. Six to 107. of young
adults infected with hepatitis Bin the United States fail to
eliminate the virus and become persistently infected (chronic HBsAg
carriers). It is estimated that there are 0.7 to 1.0 million
chronic carriers of hepatitis B virus in the United States and more
than 170 million in the world.
In the United States and Northern Europe, hepatitis B virus infects

mainly adults, while children are most affected in developing areas
of the world. In both cases, the virus is maintained in populations
primarily by transfer of infection from chronic carriers. Such
spread is effected through blood transfusion, exposure to
contaminated needles or instruments, through sexual contact and by
spread from carrier mother to infant in the perinatal period.
Hepatitis B surface antigen is the main component of the outer

envelope of the 42 nm hepatitis B virus. Excess HBsAg is also
produced in particles that are 18-22 nm in diameter. HBsAg has been
found in the blood and other clinical specimens including saliva,
urine, bile and feces of infected persons.
Antibodies to HBsAg (anti-HBs) have been shown to be protective

against infection with HBV. A safe and effective hepatitis B
vaccine comprised of hepatitis B surface antigen (HBsAg) purified
from the plasma of human carriers of the virus is commercially
available. An attractive alternative to human plasma as a source of
HBsAg is the use of recombinant DNA technology to effect synthesis
of HBsAg by a culture of microorganisms. Vaccine prepared from
yeast by recombinant DNA technology was shown to be safe and
antigenic in monkeys and chimpanzees and also protective in
chimpanzees subsequently challenged with infectious hepatitis B
virus.
7
8. CLINICAL STUDIES
From July 1983 to January 1986 RECOMBIVAX HB was administered to

approximately 3800 participants enrolled in 50
clinical studies to assess immunogenicity and safety. The
populations included in the studies are summarized in Table 1. In
addition, the four studies in infant~ born to carrier mothers were
designed to assess protection from chronic infection.
The vaccine was administered as a series of three intramuscular

injections.-- The first two injections were given one month apart
followed by a third or booster injection given six months after the
first dose.
Vaccine recipients were asked to report their temperature and any

injection site or systemic sequelae that occurred within a five day
period following each injection of vaccine.
Post-vaccination blood samples were obtained for the determination

of antibody to hepatitis B surface antigen (anti-HBs), other
hepatitis B virus serologic markers (HBsAg, anti-HBc), serum alanine
aminotransferase (ALT) activity, and in some instances, antibody to
yeast antigens.
1. SAFETY
The vaccine was proven non-infectious for man in a human safety

test in which a single 1.0 ml dose of vaccine containing 10 mcg
of HBsAg was administered to each of five initially
seronegative persons who were followed serologically for 6
months for appearance of markers of hepatitis B infection. No
markers were detected.
RECOMBIVAX HB has been well tolerated. There have been no

serious or alarming reactions directly attributable to vaccine
reported among subjects who participated in the clinical
studies. The types and incidence of complaints which were
reported within five days following administration of 3258
injections of vaccine to 1252 healthy adults who participated
in clinical studies for which analysis has been completed are
summarized in Table 2. Injection site and systemic complaints
were reported following 17~ and 15~ of the injections,
respectively. Comparable rates of systemic reactions were
observed in controlled clinical studies using plasma-derived
vaccine in both the immunized and placebo groups. The most
frequent specific injection site reactions were soreness, pain
and tenderness. The most frequent systemic complaints were
fatigue/weakness and headache.
..
8
In the clinical trials, no cases of anaphylaxis, severe

bronchospasm or laryngeal edema were reported. There were 3
reports of urticaria, one of facial edema and 16 reports of
"rash'". Antibodies to yeast have been observed both pre- and
post-immunization. Testing for serum IgG and IgE antibodies to
yeast proteins in individuals with allergic reactions indicated
no correlation between antibody responses to yeast antigens and
allergic reactions.
The frequency of clinical complaints reported within five _days

following administration of 231 injections of vaccine to 80
healthy children (3 months to 11 years) for which analysis has
been completed are summarized in Table 3. Systemic complaints
including fatigue, weakness, diarrhea and irritability were
reported following 14~ of the injections. Injection site
complaints consisting principally of soreness were reported
following 2~ of the injection.
2. IMMUNOGENICITY
Clinical studies have demonstrated that Hepatitis B Vaccine

(Recombinant) induces protective levels of antibody in greater
than 901. of healthy individuals who received the recommended
three-injection regimen. A protective antibody level has been
defined as 10 or more milli-International Units/ml (mIU/ml) as
determined by (b)(4)
Anti-HBs responses of 511 healthy adults 20- 69 years of age, 83

healthy children, and 53 dialysis patients are summarized in
Table 4 . The doses used were 3 x 10 mcg for adults, 3 x 5 mcg
for children and 3 x 40 mcg for dialysis patients.
Antibody response to the vaccine is age dependent. The younger

the vaccinee, the greater the likelihood of an immune response
developing. Antibody seroconversion rates for children 1 to 10
years of age were 100~ with Geometric Mean Titer (GMT) of
15,966 mIU/ml. Seroconversion rates for adults ranged from 95~
to 99~ for those 20 to 39 years of age and 91~ for those 40
years of age or older. The Geometric Mean Titers (GMT) were
1707 mIU/ml for the 20-29 year age group and 484 mIU/ml for the
40-49 year age group. Immunocompromised persons respond less
well to the vaccine than do healthy individuals . Sixty- eight
percent of predialysis and dialysis patients who received three
40 mcg doses of vaccine developed protective level of antl-HBs
and had a GMT of 178 mIU/ml.
Preliminary data from a double - blind. randomised, controlled

study in healthy adults comparing this product and the
currently licensed plasma-derived vaccine show at nine months
comparable seroconverslon rates of 91~ (40/44) for the
9
recombinant vaccine and 93~ (38/41) for the plasma-derived

one. The GMT (402 mIU/ml) seen in these recipients of the
recombinant vaccine was less than half that seen in the
recipients of the plasma-derived vaccine (1676 mIU/ml).
3. EFFICACY
The protective efficacy of RECOMBIVAX HB has been demonstrated

in neonates born to mothers positive for both HBsAg and HBeAg.
In two clinical studies of infants who received the recommended
one injection of hepatitis B immune globulin at birth followed
by a three injection regimen of vaccine, efficacy in prevention
of chronic hepatitis B infection was 93~ in 40 infants at 6
months in one study and 93~ in 57 infants at nine months in the
other study.
VI. ADVISORY PANEL CONSIDERATION.
Data concerning the manufacture, safety and efficacy of Hepatitis B

Vaccine (Recombinant) for the prevention of hepatitis B were discussed at
the Vaccines and Related Biological Products Advisory Committee meeting
on June 7, 1984, October 4, 1984 and April 3, 1986.
VII. APPROVED PACKAGE INSERT
A copy of the approved package insert is attached. (Exhibit 1)
Ira Berkower, M.D.

Chainnan
11iJ ~
Neil Goldman, Ph.D. Barbara C. Meyer
-t ~.J...U_ (h_ ()c....J..._ ~ 6 4~
l i ~ t h B. Paul Linda A. Smallw~~h.D.
. .
TABLE 1
PERSONS INCLUDED IN CLINICAL STUDIES OF HEPATITIS B

VACCINE (RECOMBINANT) BETWEEN JULY 1983 AND JANUARY 1986
No. Vaccinated
Populations (?:_l Injection)
Health Care Personnel/ Other 2414

Healthy Adults
Healthy Teenagers 165
Healthy Infants/Children 258
Dialysis/Predialysis Patients 288
Infants of Carrier Mothers 289
Other Groups 447
Mentally retarded
institutionalized patients
Patients with thalassemia, hemophilia,
or sickle cell anemia
Hyporesponders or nonresponders to
plasma-derived vaccine
Prei1T111une adults
Chronic carriers of HBsAg
TABLE 2
FREQUENCY OF CLINICAL COMPLAINTS WITHIN 5 DAYS FOLLOWING

ADMINISTRATION OF 3255 INJECTIONS OF HEPATITIS B
VACCINE (RECOMBINANT) TO 1252 HEALTHY ADULTS
· % of Injections
Clinical Complaint With Complaint
INJECTION SITE
Injection site reactions consisting 16.7
principally of soreness, and including
pain, tenderness, pruritis, erythema,
ecchymoses, swelling, warmth, and
nodule formation.
BODY AS A WHOLE
Fatigue/weakness 4.2
Headache 4 .1
Fever (~l 00°F} 3.2
Malaise 1.2
Sweating 0. 5
Achiness 0.4
Sensation of warmth 0.4
Lightheadedness 0.3
Chills 0.2
Flushing 0.2
DIGESTIVE SYSTEM
Nausea 1.8
Diarrhea 1.1
Vomiting 0.3
Abdominal pains/cramps 0.3
Dyspepsia 0.2
Diminished appetite 0. 1
RESPIRATORY SYSTEM
Pharyngitis 1.2
Upper respiratory infection 1.0
Rhinitis 0.8
Influenza 0.3
Cough 0.2
TABLE 2
(Continued)

ADMINISTRATION OF 3255 INJECTIONS OF HEPATITIS 8
VACCINE (RECOMBINANT} TO 1252 HEALTHY ADULTS
% of Injections
NERVOUS SYSTEM
Vertigo/dizziness 0.5
Paresthesia 0. 1
INTEGUMENTARY SYSTEM
Pruritis 0.3
Rash (non-specified) 0.2
Urticaria 0. 1
MUSCULOSKELETAL SYSTEM
Arthralgia including monoarticular 0.5
Myalgia 0.4
Back pain 0.2
Neck pain 0.2
Shoulder pain 0.2
Neck stiffness 0.2
HEMIC/LYMPHATIC SYSTEM
Lymphadenopathy 0.2
UROGENITAL SYSTEM 0.2
CARDIOVASCULAR SYSTEM 0.2
PSYCHIATRIC/BEHAVIORAL
Insomnia/Disturbed Sleep 0 .1
SPECIAL SENSES
Earache 0.2
TABLE 3

VACCINE (RECOMBINANT) TO 80 HEALTHY. CHILDREN
% of Injections
INJECTION SITE
Injection site reactions consisting 2.2
principally of soreness
BODY AS A WHOLE
Fatigue/weakness 3.0
Headache 0.8
Sweating 0.4
Bruise from venipuncture 0.4
Illness 0.4
DIGESTIVE SYSTEM
Diarrhea 2.0
Vomiting 1.3
Diminished appetite 0.4
Loose stool 0.4
Nausea 0.4
Teething 0.4
RESPIRATORY SYSTEM
Upper respiratory infection 2.6
Pharyngitis 0.8
Rhinitis 0.8
Cough 0.4
Croup 0.4
INTEGUMENTARY SYSTEM
Papular Rash 0.8
Rash (non-specified) 0.4
Urticaria 0.4
TABLE 3
(Continued)

VACCINE (RECOMBINANT) TO 80 HEALTHY. CHILDREN
% of Injections
PSYCHIATRIC/BEHAVIORAL
Irritability 1. 7
Insomnia/Disturbed Sleep 0.4
INFECTIOUS SYNDROMES
Viral infection 1. 7
SPECIAL SENSES
Otitis media 0.4
TABLE 4
ANTIBODY RESPONSES AT 7/8 MONTHS AMONG HEALTHY INDIVIDUALS

ANO DIALYSIS PATIENTS WHO RECEIVED THREE INJECTIONS OF
HEPATITIS B VACCINE (RECOMBINANT) AT 0, 1 ANO 6 MONTHS
% Seroconversion GMT(mIU/ml)
Population Age No. Dose mIU/~10 mIU/ml~lO
Healthy Individuals 1 - 11 yrs. 14 5 mcg 100 15966. 0

12 - 19 yrs. 69 10 mcg 100 2913.4
20 - 29 yrs. 344 10 mcg 99 1737 .0
30 - 39 yrs. 111 10 mcg 95 730.0
~40 yrs. 56 10 mcg 91 586.5
Dialysis Patients ~20 yrs. 53 40 mcg 68 178 .1

Page 2
Vol ume Starting

Page
III. 6) 2t Vaccine (Cont.)
B. Inrnunogenicity Studies (Cont.)
4. D1alys1s and Pre-dialysis Patients 2 00694
a. Sunmary
c. Synopses
d. Individual Study Sunmaries
5. Mentally Retarded Institutionalized 3 00827
Patients
a . · SUiiiila 7y
b. Synopses
c. Individual Study Sunmaries
6. Thalassemics and Hemophiliacs 3 OOB!Z
a. Synopses
b. Individual Study Sunmaries
7. Nonresponders and Hyporesponders 3 QD§Z~
a. Sunmary
b. Synopses
c. Individual Study Sunmaries
8. Prei11111une Adults 3 00956
a. Sunmary
b. Synopses
c. Individual Study Sunma ri es
9. Chronic Carriers (HBsAg) 3 00984
a. Synopsis
b. Individual Study Sunmary
C. Efficacy 3 Qlf!06
1. Sunmary
2. Synopses
3. Individual Study Sumar1es
4. Appendix (Antibody Equivalence)
IV. References 3 lUQa!
2,H,91/2
1 /1 b/86
rm:a ::n:· ... ,
00001
BRIEF SU,..ARY OF YEAST RE.COMBINANT HEPATITIS 8 VACCINE CLINICAL REPORT
I. CLINICAL ANO SCROLOGI C DATA
Number Vaccinated Clin1 ca 1 Re~2rt~ SrrolQgic Otta

>1 3 >1 3 >1 3
Study Population InJect1on · InJec;t1ons Injection Injections lniection Injections
Health Care Personnel/
Other Healthy Adults 2414 1442 1626 990 1616 1048
Healthy Teenagers 165 165 16S 165 165 165
Healthy Infants/
Children 258 122 220 100 213 97
Oialysis/Predialysis
Pat ients 288 196 286 184 258 166
Other Groups 736 362 581 110 bJ3 80
I I. IMMUNOGENICITY
Ant i body responses across all dose levels used are sulffllilr1zed below:
% with Anti-HBs After 3 Injections
Minimal Titer Fully Protective Titer
Study Populations (S/N ~2.1) (mlU/ml ~10)

Other Healthy Adults 98 96
Healthy Teenagers 100 98
Healthy Infants/Children 100 100

01alys1s / Pred1alys1s w
Patients 94 88
*Figures apply to patients that received three 40 mcg doses in the

deltoid . See SUMMARY - DIALYSIS AND PREDIALYSIS PATIENTS for
discussion of other regimens that were less 111111Unogenic .
31771/4
l / 12/86
00002
III. CLINICAL REACTIONS

There have been no reports of serious adverse experiences attributable
to vaccination. Clinical reactions following vaccination have been mild
and transient consisting mostly of soreness at the injection site,
fatigue/weakness. headache, and nausea. Complaint frequencies across
all dose levels used are sunmarized below:
% of Injections Followed by Clinical Complaints
Local Any Temperature
Study Populations (Injection Site) Systemic Complaint ~100°F (Oral)

Other Healthy Adults 17 15 27 3
Healthy Teenagers 5 2 6 0.2

Healthy Infants/Children 2 9 11 11
Dialysis/Predialysis
Patients 3 8 10 5
IV. EFFICACY
Passive-active prophylaxis consisting of hepatitis 8 i11111une globulin
and yeast recombinant hepatitis B vaccine was 98% effective in
preventing chronic hepatitis 8 infection among infants born to mothers
positive for bo_th HBsAg and HBeAg (59 infants evaluated at six months).
3177 I/3
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00003
GENERAL SUMMARY
C1 inica1 studies with the yeast recombinant hepatitis B vaccine were initiated
in July 1983. This document includes data from studies concerned with the
vacci ne's safety, i11111unogenicity and efficacy which were generated to support a
1 icense for the vaccine in the· United States. · Su111T1aries and · analyses across
studies of cl inical complaints and serologic responses are based on data encoded
within the project database by October 15, 1985. However, several individual
study summari es are derived from more recent data that have not yet been entered
in the database.
VACCINE
A total of 28 lots of yeast recombinant hepatitis B vaccine have been prepared

by Merck and Co .• Inc., accordiing to procedures developed in the Merck, Sharp
and Dohme Research Laboratorie:s. Eighteen of the lots are in use in human
clinical trials (see Appendix I) . All clinical data received to date inrtic:ate
that the vaccine is safe. One of the lots (C-J625) was made usinQ (b) (4)
(b) (4) procedure and was (b) (4)
The clinical and serologic data. relating to this lot will be surrmarized sepa-
rately , beca use this orocedure will not be used in making corrmercial vaccine
(see section entitled (b) (4) VACCINE). The remainder of the lots were
made using a (b) (4) procedure and are in cl in i cal t rials
under BB IND 1925 .
CLINICAL STUDI ES
Table I lists 50 clinical stud·ies involving the yeast recombinant hepatitis B

vaccine produced by the (b) (~) procedure that are currently in progress .
In most of the studies, participants r eceive the vaccine as an intramuscular

i njection administered at 0, 1 and 6 months . However, chronic carriers of HBsAg
a nd ce r tain groups of dialysis patients receive a total of 6 doses of vaccine
admini stered at monthly i ntervals, while persons with prior i rrmunity a nd sub-
jects i n the study designed to demons t rate noninfec t ivity of the vaccine are
give n on l y a single dose of ~raccine . Patients with hemophilia receive the
vacc i ne as a subcutaneous injection . Each dose of vaccine (total mcg of HBsAg
administered at a given time) is generally contained within a single i njection.
However, each 40 mcg dose given to dialysis and predialysis patients cons i sts of
a pair of 20 mcg injections.
The numbers of subjects'who have received first, second and third injections of
the yeast recombinant hepatitis B vaccine are shown by population i n Tabl e 2. A
total of 3861 partici pants have received one or mo r e i nject i ons of vaccine,
while 2309 individuals have completed a 3 dose reg i men of vaccinat i on .
Vaccinees in all studies are asked to record their temperature daily and to
record any local or systemic complaints that they may have for 5 days follow ing
each injection of vaccine. Table 2 also shows by population the number of
s ubjects for whom post vaccination clinical reports a r e currently avail a ble.
Clinical reports following the first injection have been received for 2878
0000 4
vacc inees, while 1571 report s are available for subjects who have received 3
doses of vaccine.
Postvacci nation blood samples are obtained for the determination of antibody to
hepatitis B su rface antige!n (anti-HBs), other hepatitis B virus serologic
markers, a lanine aminotransferase (ALT), and antibody to yeast antige ns. Table
2 also shows by population the number of subjects for whom postvaccination
anti - HBs data are available. Anti - HBs titers are known for 1551 subject s
following 3 doses of vaccine and a r e available for an additional 1334 individu-
als following only the first or second injection of vaccine.
IMMUN0GEN I Cl TY
Anti-HBs Assay
l111'11une responses to vacci ne are measured us i ng a radio i rrrnunoassay (b) (4)

(b) (4) to detect antibody {anti - HBs) specific for t he hepatitis B vi r us sur face
antigen (HBsAg) . Two different cutoff val ues have been utilized in detennining
a positive antibody respon:se ; one to indi cate seroconver sion , the other an
attempt to define a minimum level of antibody clearly indicative of protect ion
from cl i ni ca 1 infection. The lower cutoff is taken as a ratio of sample counts
to negative control counts (S/N) >2.1. The higher cutoff define s as posi t ive a
sample having an anti - HBs titer i n milli-I nternational Units/ml (mIU/ml) >10 .
Anti-HBs t i ters expres sed as, S/N ratios cannot be converted dire ctly into un i t s
of mlU/ml . However, the bro sea les of measurement are fairly similar at 1ow
titers (i.e. S/N of <10 is approximately the same as an mlU/m1 of <10). There
is a developing concensus that views an anti-HBs titer of S/N or mTlJ/ml >10 as
fully adequate for protection against hepatitis B. (Centers for Disease Control:
Recommendations for protect'ion against viral hepatitis . MMWR 34 (22):313- 335,
J une 7, 1985) -
Anti-HBs responses among healthy , initially seronegative persons rece i ving yeast
r ecombina nt hepatitis B vaccine (b) (4) procedure) at 0 , 1 and 6 mon t hs ,
and for whom post vacci nation anti-HBs are available in units of mIU/ml, are
summari zed in Tables 3 to 6. Additional tabulati ons and discussions of antibody
responses for these and other groups will be found i n the population- specific
summaries. Very br ief accounts of the irrmune responses of each population are
given in the following paragraphs of this general su11111ary.
Hea lth Ca re Personnel/Other Healthy Adults
Thirty - six s t ud i es are in progress involvi ng 2414 health care personnel or other
hea lthy adults. Participants receive a dose of the recombinant vaccine (2 . 5, 5,
10 or 20 mcg) at 0, 1 and 6 months . Fourteen hundred and forty - t wo (1 442)
persons have completed a 3 injection regimen of vaccination . Anti - HBs responses
following the third injection have been measured for 1048 subjects and respons es
fol l owing only one or t wo injections have been measured for an additional 568
vaccinees.
Tables 3 to 6 surrrnarize thE~ anti - HBs responses of 801 adults , 20-69 yea rs of
age, who received 2.5, 5, 10 or 20 mcg doses of vaccine , and for whom data a r e
available reported in units of mlU/ml. At 7/8 months (1-2 months after t he
third in j ection) , 97 - 100~ of the vaccinees had an anti - HBs titer of S/N >2.1 ,
while 89 - 97 % achieved a protective titer of mIU/ml >10 (Table 5) . At 12 months ,
00005
92-97% of the vaccinees still had an anti-HBs titer of S/N >2.1, while 74-90%
(86-90% of those receiving doses of 10 mcg or more) had titers of m!U/ml >10
(Table 6). -
The level of anti-HBs attained after 3 injections of vaccine does increase with
dose level (Table 5). Agei and sex also influence the antibody response to
vaccine. Anti -HBs levels a1re inversely related to age, while females tend to
develop higher antibody tit,e rs than males (see SUMMARY - HEALTH CARE PERSONNEL
AND OTHER HEALTHY ADULTS for statistical analysis of these factors).
For healthy adults as a group, a vaccination regimen consisting of three 10 me~
doses is sufficient to induce fully protective titers of antibody (mlU/ml .?_10)
in 97% of the vaccinees.
Healthy Teenagers
The vaccine has been admin·istered at 0, 1 and 6 months to 165 seronegative,
healthy teenagers (all male mil i tary recruits mostly 17-19 years of age) .
Subjects received 2.5, 5 or 10 mcg doses. All of the vaccine recipients had
anti-HBs titers of S/N >2.1 by 7 months regardless of dose level. Using a
cutoff of mIU/ml >10, 1001" of subjects receiving 10 or 5 mcg doses were antibody
positive, while 94i of those receiving 2.5 mcg doses had antibody at that time .
Response level ( titer) was found to increase significantly with dose level (see
SUMMARY - HEALTHY TEENAGERS for details of the statistical analysis ). At each
dose level, the geometric mean antibody titers attained by teenage subjects
fol lowing 3 doses of vaccine were greater than those developed by young adults
{Table 5) . At 12 months, 100% of those who received 10 or 5 mcg doses of
vaccine have antibody, while 91 % of those who received 2.5 mcg doses continue to
have protective levels of anti-HBs.
Healthy Infants/Children
To date, a total of 258 healthy infants and children, 3 months to 11 years of
age, who were negative fo1r hepatitis B markers, have been vaccinated with
hepatit is B recombinant vaccine. Seven to 8 month serology data are available
on 97 infants and children. Antibody responses to 5, 2.5 and 1.25 mcg doses of
the vaccine administered at 0, 1 and 6 months were evaluated . The vaccine was
very immunogenic in this population. Seroconversion {S/N >2 . 1) exceeded 94%
after 2 doses regardless of dose level. Protective levels of antibody {mIU/ml
>10) were induced in 10oi of vaccine recipients , one month after the third
Tnjection, regardless of dose level administered. Statistical analysis of data
from study 809 showed that both log dose level and the age of the child were
related to antibody titer ( see SUMMARY - HEAL THY CHILDREN for details of the
statistical analysis ) . Titers increased with log dose level, and younger
children had higher titers than older children. As shown 1n Table 5, the GMT of
anti-HBs at 7/8 months in children receiving 2.5 or 5 mcg doses of vaccine
(based on study 809 only) were higher than those developed by teenagers receiv-
ing comparable dosages. At 12 months, all children surveyed still had titers of
mIU/ml >10.
Dialysis and Predialysis Patients
Five studies are in progress involving 288 patients with chronic renal insuffi -
ciency. Two hundred ten patients are rece iving dialysis treatments {dialysis
patients), while 78 are not yet receiving such treatments (predialysis
OOOOE>
patients). Predia lysis pat·i ents receive an i njection of the yeast recombinant
hepatit i s B vaccine (10, 20, or 40 mcg dose) at 0, l, and 6- months . Dia lysis
patients receive an injection of the vaccine (20, 40 or 100 mcg dose) either at
0, 1, and 6 months or according to a more intensified regimen (20 or 40 mcg
dose) at 0 , l, 2, 3, 4 and 5 months. In four of the studies, patients received
the vaccine as an intramuscular injection i n the deltoid. However , in one
study , vaccine was administered in the buttock.
One hundred forty-seven dialysis patients and 52 predialysis patients have

completed a three injection regimen of vaccination, and 34 di alysis patients
have completed a six injection regimen. Serologic data following the last
injection of vaccine are cu1rrently avai l able for 50 predialysis and 84 dialysis
patients who received three injections of vaccine and 32 dialysis patients on
the six i njection regimen. Because of the multiplicity of regimens utilized,
antibody responses are sunma.rized below in tabular fonn:
Inject. % with Anti-HBs (# Evaluated)
Pa t ient Regimen Dose Site 7/8 Months 12 Months
Group ( # Doses) (mcg) (B/0) ~/~ >2.I mIO/ml 2,IO S?N >2.1 m1U7m1 >Hl
Predialysis 3 10 D 15 ( 13) 15 (13) 8 (12) 0 (12)
20 D 68 (19) 58 (19 ) 71 (14) 50 (14)
40 D 67 ( 18) 61 ( 18 ) 40 (10 ) 40 ( 10)
Dialysis 3 20 D 59 (29) 48 (29) 52 (29) 41 (29)
40 D 94 ( 17} 88 ( 17} 81 (21) 71 (21)
40 8 64 (36) 58 ( 36) 65 (37)** 54 ( 37}**
6 20 B 56 (16 )* 44 (16)* 50 (18)** 44 (18)**
40 B 69 (16)* 69 (16)* 67 (15) ** 60 (15 )**
* 6 months
** 10 months
8 "' buttock
D = Deltoid
Serologic data are currentl.Y available following two injections of vaccine for
dialysis patients receiving 100 mcg doses. At three months, 68% (19/ 28) had
antibody (S/ N 2_2.1), while 2'5% had a fully protective titer (mIU/ml2:10) .
In summary, predia lysis and dialysis patients do not respond to the vaccine as
wel 1 as healthy adults. Responses to the vaccine among patients impr oved with
increasing dose and were better with administration in the deltoid as opposed to
the buttock. Responses to the three injection and intensified six injection
regimens of vaccination appe!ar to be similar.
Mentally Retarded Institutionalized Patients
One study is in progress in1:::luding 202 mentally retarded individuals. Partici-

pants receive a 10 mcg or 20 mcg dose of the recombinant vaccine at 0, land 6
months . Two hundred persons have completed a three injection reg i men of vac-
cination. Anti-HBs responses following only one injection are available for 201
vacci nees. At 1 month 19- ~~0% had an anti - HBs titer of S/ N >2 . 1 , while 8- 11%
achieved a protective titer of mIU/ml 2.10. -
00007
Thalassemics/Hemophiliacs
Thirty-one thalassemic children (<16 years of age) have received intramuscular
injections of yeast recombinant hepatitis B vaccine in a single study. Among 15
children who received threei 5 mcg doses, 89% had at least minimal evidence of
anti-HBs at 7 months (S/N >2 . 1), while 78% had fully protective titers (S/N
>10). Twe l ve children have received three 2.5 mcg doses of vaccine. At 7
months, all had titers of S/N >10.
Fifteen patients with hemoph i lia have been vaccinated subcutaneously in a single
study. Twelve subjects under 20 years of age who received two 5 mcg doses all
had protective levels of antibody by 3 months (m!U/ml >10). Three patients >20
years of age have received 10 mcg doses of vaccine. At 3 months, 2 of these
patients had seroconverted (S/ N >2 . 1) . but neither had achieved a protective
level of antibody (rn!U/ml 2_10). -
Nonresponders/Hyporesponder:s/ Trans i ent Responders
Six studies are in progress invo l ving 55 healthy adults and 26 dialysis patients
who failed to develop de1tectable anti-HBs after three injections of plas-
ma-derived hepatitis B vacdne. The studies also include five healthy adults
who were hyporesponders or transient responders to the plasma-derived vaccine.
Nonresponders receive an injection of the yeast recombinant vaccine (10 or 20
mcg doses for healthy individuals and 40 mcg doses for dial ysis patients) at o.
1 , and 6 months . Hypo res ponders and transient responders receive a s i ngle
injection containing 10 mcg of the yeast recombinant hepatitis B vaccine.
Thirty nonresponders (24 healthy adults and six dialysis patients) have complet-
ed the three i njection reg i men of vaccination. Anti - HBs {S/N >2.1) was detect-
able in 79% ( 11/ 14) of the adults measured at 7-9 months, while 50% had protec-
tive titers (mlU/ml >10). Two of four dialysis patients monitored at 7-9 months
developed antibody tTters of mIU/ ml ~10.
Three of four hyporespondlers/transient responders had protective titers of

anti-HBs one month after receiving a dose of the yeast recombinant vaccine.
Preimmune Adults
Two studies are being c~nducted to examine the response of adults, who have been
documented to have hepatitis B antibody at some time in the past, to a single 5
or 10 mcg booster injecti1on of yeast recombinant hepatitis B vaccfoe. Six-
ty-three persons have rece·ived a 10 mcg dose of vaccine. Ninety-seven percent
of those participants whosi~ anti-HBs responses were measured approximately one
month fol lowing the booster demonstrated a boost in titer at that time. One
individual who was antibody negative just prior to the booster injection failed
to develop detectable antibody. Twenty-eight individuals received a 5 mcg
booster injection. All of 25 participants tested at one month after the in-
jection demonstrated a boost in anti-HBs titer .
Chronic Carriers
One study is being conducti~d to detennine whether vaccination can eliminate the
carrier state. Eighteen adult chronic carriers (positive for HBsAg for at least
one year) have been scheduled to receive six 10 mcg doses of recombinant
hepatitis 8 vaccine at monthly intervals. Three participants have received all
000 0 8
six doses; eighteen have received at least four doses. Administration of the
remaining doses continues in progress. To date, none of the carriers has become
negative for HBsAg.
Anti-HBs Subtype Specificity
Four major subtypes of the hepatitis B virus are known with respect to the
antigenic composition of HBs.Ag. The subtypes _are _designated adw, adr, ayw, and
~ - All of the subtypes have the common ant1gen1c detenninant a, and anti-HBs
specific for the a detenni1nant of HBsAg would be expected tobe protective
regardless of the subtype of the challenging virus.
The immunizing component of the yeast recombinant hepatitis B vaccine is HBsAg
of subtype ad. Assays were perfonned to ascertain that anti-HBs induced by the
vaccine in numan subjects i:s largely specific for the a detenninant of HBsAg .
Postvaccination serum samplE~s with anti-HBs titers of 25 mlU/ml or more from
subjects in several studies were tested to determine the percentage of antibody
specific for the a and d determinants of HBsAg. Table 7 shows the results of
these assays. Antibody- spi?cific for the a determinant predominates. By 3
months (2 months after the siecond dose of vaccine) the mean percentage of anti-a
in all sera tested was 90%. The percentage of anti-a continued to increase with
time and reached 95% at 7/8 months {l to 2 months after the third dose of
vaccine) .
SAFETY
The vaccine has been well tolerated . There have been no reports of serious or
alanning reactions attributable to vaccine. To date there have been 7 reactions
that are possib l y related to the vaccine. Five of these reactions are described
in table 8 which lists reports of experiences among vaccine recipients that have
been filed with the OoBRR. The other two reactions which are not described in
Table 8 are surmiarized below:
1. A 23 year old female devi~loped hives within 24 hours of receiving the first
injection of vaccine. The hives were described as one large 3- 4 inch lesion ,
pruritic, with severa l satellite lesions on the back and several small
lesions on the leg·s. }\11 symptoms resolved by day 4 post vaccination.
Within 24 hours of rece ·i ving the second injection of vaccine the subject
developed sma 11 hives on the back, arms, and 1eft hand . A11 symptoms re-
so 1ved by day 4 post vaccination. The individual received her third in-
jection of vaccine with no evidence of hives. In the past, the subject
developed hives during administration of contrast dye (for CAT scan) . There
is no other allergic history.
2. A 40-year old female devE?loped a few ecchymotic flat lesions on the lateral
aspect of her breasts, bilaterally , four days after the first injection of
vaccine. Over the following two days the lesions increased. Vomiting
occurred on the third day. All symptoms disappeared over the next 36 hours,
and the subject has rernained well. There was no fever, and WBC, Hgb,
platelets, and coagulation profile were normal. The patient has no history
of allergies to exogenous substances . No further vaccine was administered to
this patient.
oo ooq
Table 9 summarizes the most freq uent injection site or systemic complaints
reported by healthy adult vaccine recipients . Injection site and systemic
compla ints were reported with frequencies of 17% and 15%, respectively. The
most freq uent specific injec.tion site reactions were soreness, pain, and tender-
ness. The most frequent sp1?cific systemic complaints were fatigue/weakness and
headache (see SUMMARY - HEALT~l CARE PERSONNEL AND OTHER HEALTHY ADULTS for a more
detai l ed listing of clin i cal complaints).
ln add1tion to monitoring clinical compla i nts, recipients of the yeast

recombinant hepatitis 8 vaccine were also followed for antibody to yeast anti -
gen, e l evations of alani ne aminotransferase , and acquisition of the hepatitis 8
virus serologic markers HBsAg and anti - HBc . Since the yeast recombinant
hepatitis B vaccine does not invo l ve intact hepatitis B virus at any stage of
its formulation , and it also cannot contain core ant i gen, post-vaccination
assays for HBsAg and anti-HBc were included only to detect possible breakthrough
hepatitis 8 infections or infections that might have been in an early stage of
incubation when vaccination was initiated.
Antibody to Yeast Antigen
In order to l ook for antibody to components of the yeast used to prepare the
vaccine, sera from va ccine recip i ents were tested by radioimmune assay. The
yeast antigens utilized in the assay were derived from the parent strain of S.
cerevisiae used for the prc,duction of HBsAg. This strain does not contain the
gene for HBsAg. Sera from 133 vaccine recipients (adults and children) were
tested for antibodies to :yeast antigen. One hundred percent of individual s
tested had anti -yeast IgG fo both pre and postvaccination sera. The titers in
prevacc i nation sera ran9ed from 12,000 to 104,000 antibody units.
Postvaccination anti-yeast IgG titers fluctuated over time with some increasing
and others decreasi ng. However, a statistical test failed to show any
significant trend in postvacc ination anti-yeast titers of antibody (Table 10)
There was also no association found between changes in the titer of anti -yeast
antibody and the incidence of c l inical complaints following vaccination (Table
10) .
The most prominent yeast antigen found in preparat i ons of the yeast recombinant
hepati tis B vaccine is designated P60 . Antibody to P60 is detected and
semi-quantitated using a Western blot assay. Prevaccination and 3 month
postvaccination sera from 42 individuals have been assayed for antibody to P60.
There were no statistically signi fi cant associations between the level of
antibody to P60 and the incidence of clinical complaints follow ing vaccination
(Table 11).
Alanine Aminotransferase (ALT)
All subjects enrolled in a clinical study have pre - vaccination ALT levels
determined. To date, one ,,r more post-vaccination levels have been obtained in
most individuals. Thirty-•one subjects, whos~ pre-vaccination ALT levels were
norn~l. had e l evated levels of this enzyme (1.5 - 7.0 times the upper limit of
normal ) a t some time during a 7- 8 month period of observation following vac-
cination. Elevations were transient in 22 cases. For 3 subjects, transient
elevations in ALT were attributed to infectious mononucleosis, cholecystitis , or
non A non B hepatitis. In all other instances , a reason for the ALT elevation
was not ascertained. None of the subjects has shown any clinical or serologic
signs (HBsAg or anti-HBc) of hepatitis B. For the remaining 9 subjects, one
00010
participant 1 s follow-up serum samp le showed a decreas ing ALT, and the other
individuals have no follow-up se1ra available. These 9 individuals have shown no
clinical or serologic signs of hepati tis 8 .
Two additional subjects had fluctuations in ALT levels. In both cases the
prevacc1nation samples were elevated (1.5 - 2 times the upper limit of normal).
After vaccination, the levels r1eturned to normal, increased, and then began to
decrease. In one case, a 4.5-f()ld increase in ALT was noted a t 2 months after
vaccination. At 3 months the ALT level was 2-fold higher than normal. In the
second case a 3.5-fold increase in ALT was seen at 6 months. AT 7 months it was
2-fold higher than normal. No reason for the ALT elevation could be ascer-
tained. No follow-up sera are available. Neither participant has been reported
to show any clinical or sero l ogic signs of hepatitis B.
Sporadic transaminase elevation$ may result from a variety of causes including
minor muscle trauma (such as that caused by exercise and by intramuscular
injections), common infection (including viral and mycoplasmol infections),
drugs (including aspirin), and alcoholic beverages. In a previous clinical
trial of plasma-derived hepatitis B vaccine, about one percent of the vaccine
and the placebo recipients had el evated ALT levels at each testing. The
elevations were sporadic; thos,e with an elevated ALT at any given time were
generally not the ones with an elevation at the next testing time. Elevations
among recipients of the yeast recombinant vaccine have been similarly sporadic
and of low incidence. We do not believe that the transaminace elevations that
have occurred are likely to have been caused by the yeast recombinant hepatitis
B vaccine.
HBsAg
The Interim Submission reported 2 initially seronegative vaccine recipients for
whom a single postvaccination serum sample gave a marginally positive test for
HBsAg (S/N ~2 . 1).
In one case, the 3 month postvaccination serum from a healthy teenager tested
just above the cutoff for HBsAg (S/N = 2.11). However, the prevaccination. 1,
6, and 7 month postvaccination samples were negative for HBsAg. The individual
had normal ALT levels and all serum samples were negative for anti-HBc. It
seems likely that the low positive test was spurious.
The second case is an adult health care professional. The subject's 6 month
postvaccination serum gave a low positive test for HBsAg (S/N = 2.4). However,
a subsequent retest of this serum sample tested negative for HBsAg. The
prevaccination sample and all other postvaccination samples through 8 months of
follow-up have been negative for HBsAg and anti-HBc and all samples have had
nonnal ALT levels.
Anti-HBc
A total of 18 participants had serum samples positive for anti-HBc at some tin-e
during the study period. Five of the individuals had prevaccination samples
positive, while 13 had positiv,~ postvaccination samples. A brief description of
each case follows.
00011
Healthy Adults
Two subjects had prevaccination serum samples positive for anti - HBc. In one
case, the anti-HBc was transient. In the other case, all but one serum sample
taken after vaccination rema.ined positive, Serum samples for these individuals
have remained negative for HBsAg and there has been no report of clinical
i 11 nes s.
One healthy adult was reported in the Interim Submission to have had a 2 month
postvaccination serum samplE! positive for anti-HBc . The same serum sample was
reported negative on retes1t. A11 subsequent samples through 12 months were
negative. In two additional adults, the 6 and 8 month serum samples,
respectively, were borderline positive for anti - HBc. All previous serum samp1es
were negative. Both subjects remained HBsAg negative, and there has been no
report of clinical illness . Repeat testing will be done and follow-up samples
are pending.
Predialysis Patients
In the Interim Submission serum samples from 6 predialysis patients were
reported positive for anti-HBc at some time during the 7 month observation
period. Four of the 6 were transiently positive. Of the remaining 2 patients,
one was negative on retest, and one on retest was positive for anti - HBc of the
IgG class but negative for anti-HBc of the IgM class.
Dialysis Patients
Three dialysis patients had prevaccination serum samples which tested positive
for anti - HBc. For one patiient the positive anti-HBc was transient. Anti-HBc
persisted in the other two patients. None of the patients was reported to have
developed clinical illness cir become HBsAg positive.
Three dialysis patients werEi reported to have one or more serum samples positive
for anti-HBc postvaccination. In one case, the positive anti-HBc was transient.
In the second case, the 9 month sample was positive. In the third case, the 3
and 6 month samples were positive. Further samples were not available. None of
the patients was reported to have developed clinical illness.
Other Populations
The 8 month serum sample from a patient with hemophilia was r~ported positive
for anti-HBc. The pre, 1 and 6 month samples were negative. The patient has
been anti-HBs positive since 2 months. The patient has remained HBsAg negative
and there has been no report of clinical illness.
The small percentage of vaccine recipients with serum samples positive for
anti-HBc may reflect both the frequency of false positives seen with this assay
and the fact that predialysis, dialysis and hemophiliac patients receive
transfusions of blood and blood products at varying intervals during the course
of their disease. Where possible retesting will be done and follow -up samples
obtained.
000 1 2
EFFlCACY
Four studies have been initiated to evaluate the efficacy of yeast recombinant
hepatitis B vaccine in preventing chronic hepatitis B antigenemia in healthy
infants born to mothers who are positive for HBsAg and either positive or
negative for HBeAg. Two of the studies are being conducted in China, one is in
Hong Kong, and one is in the United States. ln 3 of the studies, infants
receive a single injection of hepatitis 8 i11111unoglobulin i11111ediately after birth
followed by injections of yeast recombinant hepatitis B vaccine (5 mcg dose) at
0 , land 6 months. One of these studies also includes infants that receive HBIG
plus plasma-derived hepatitis B vaccine (10 mcg dose). Two of the studies being
conducted in China include groups of infants that receive a three injection
regimen of yeast recombinant hepatitis B vaccine alone (5 or 10 mcg dose), and
one study has a group that receives plasma-derived hepatitis B vaccine (20 mcg)
without any HBIG.
To date, 412 infants have be~n enrolled in the 4 studies, 289 of these in groups
receiving the yeast recombin,ant hepatitis B vaccine. No serious adverse experi -
ences related to the vaccine have been reported.
Data are currently available for 59 infants, born to mothers positive for both
HBsAg and HBeAg, who receive a single dose of HBIG and three 5 mcg doses of the
yeast recombinant vaccine. A single infant in this group was HBsAg positive at
6 months . This infant was already antigen positive at birth. Based on these
data, the efficacy of this passive-active prophylaxis in preventing chronic
hepatitis B vaccine is estimated to be 98%.
COMPARISON OF RECOMBINANT AND PLASMA DERIVED VACCINES
The only hepatitis B vaccine currently licensed in the United States

(HEPTAVAX-B} is comprised of noninfectious HBsAg that has been purified from the
plasma of chronically infc?cted persons. By contrast, the investigational
recombinant hepatitis B vaccine is made from HBsAg produced by a strain of
baker's yeast (S. cerevisiac? ) containing that portion of the hepatitis B virus
gene which codes for surfaci~ antigen. HBsAg puri fied from yeast is essentially
the same as that from human plasma including its particle appearance. Unlike
the plasma-derived HBsAg the yeast HBsAg is not glycosylated. The recombinant
HBsAg vaccine is adsorbed to alum as is the plasma-derived product.
A direct comparison of the two vaccines with respect to i1m1unogenicity and
clinical complaints will be available from two studies. One is a small (56
participants) randomized study (#807). The results for this study are presented
in the appropriate study sulllllclry (see SUMMARY-HEALTH CARE PERSONNEL AND OTHER
HEALTHY ADULTS). The other is a double blind study in which 300 healthy adult
male homosexuals will receive three doses of either yeast recombinant (10 mcg
dose) or plasma- derived (20 mcg dose} hepatitis B vaccine . This study was
initiated recently. The first injection of vacc i ne has been administered to 197
subjects, while 113 have 1·eceived the second of three scheduled injections.
Assays for hepatitis 8 serologic markers will not be done on any samples until
subjects have received all injections of vaccine. However, interim clinical
reports submitted fol l owing the first two injections have been examined by the
clinical monitor at Merck and complaints and elevated temperatures tallied
according to the type of hepatitis B vaccine (recombinant or plasma-derived)
that was administered.
00013
Clinical complaints from the study involving homosexuals are surmiarized in Table
12. All reactions have been mild and trans ient. Among recipients of plas-
ma-derived vaccine, 39% reported injection site reactions while 31% had systemic
complaints within a 5 da:y period following vaccination. Recipients of
recombinant vaccine reported injection site reactions following 32% of the
injections, while 24% had systemi c complaints. Local complaints consisted
almost exclusively of sorenEiss at the injection site for rec ipients of either
vaccine . The most freq ue•nt systemic complaints following injection of
recombinant vaccine were fatigue/weakness (6%) , arthralgia (6%) , and nausea
{4%), while the most frequent systemic complaints following injection of the
plasma-derived vaccine were fatigue/weakness (16%), arthralgia (7%). and head-
ache (6%) .
Further comparison of the antibody and clinical responses to the plasma-derived

and yeast recombinant hepatitis B vaccine is possible using data from multiple
ongoing studies involving the recombinant vaccine and historical data obtained
in earlier studies with the plasma-derived vaccine . This type of comparison is
described below and demonstrates that both recombinant and plasma-derived
vaccines are we ll tolerated and highly irrrnunogenic. Tables 13 to 17 compare the
anti -HBs responses of hea 1th care personnel and other heal thy adults who re-
ce ived 10 mcg doses of yeast recombinant hepatitis vaccine in the current
clinical trials program with similar subjects who received 20 mcg doses of
plasma-derived hepatitis B vaccine in earlier studies. Seroconversion rates
among adults 20-49 years of age, after 3 injections of vaccine, were 94% or
greater for either vaccine ( Table 15). The GMTs of responders in this age range
were 1554.0 m!U/ml (approximate conversion from (b) (4) units) and 1282.3 mlU/ml
for recipients of plasma-derived and recombinant vaccines, respectively.
The percentages of both !Plasma-derived and recombinant vaccine recipients
developing anti-HBs {S/N >2. 1) declined with increasing age. The geometric mean
titers of responders alsovaried inversely with age. Although 94 - 99% of the
vaccinees ages 20-49 years of age had anti-HBs after 3 injections of vaccine,
the frequency of seroconversion in subjects 50- 59 years of age was 90% among
recipients of recombinant vaccine and 85t for those who received plasma-derived
vaccine. The geometric mE!an titers of anti - HBs at 7/8 months in persons
receiving recombinant vaccine ranged from 1707 mIU/ ml for the 20-29 year age
group to 442 mIU/ml in the• 50-59 year age group. The GMT for recipients of
plasma - derived vaccine was 2830 mlU/ml for the 20- 29 year age group and 306
mIU/ ml for the 50- 59 year age group (Table 15).
Table 16 shows the distribution of antibody titers achieved by healthy adult
vaccinees of all ages fo ll owing 3 injections of either yeast recombinant or
plasma-derived hepatitis B vaccine. Among recipients of the recombinant
vaccine, 98% had at least minimal evidence of antibody (S/N >2.1) . while 97%
developed fully protective levels of anti-HBs (mIU/ml >10). Eighty-nine percent
of the vaccinees had a titer of mfU/ml >100, while 5B% had a titer of mlU/ml
>1000 . A fairly similar distribution or titers was characterist ic of persons
receiving the plasma-derived vaccine. Ninety-five percent seroconverted for
anti-HBs (S/N >2.1), while 92% developed fully protective levels of antibody
(mIU/ml >10). - Seventy-eight percent of the plasma-derived vaccine recipients
had a titer of rnIU/ml _?_100, while 53% had a titer of mIU/ml 2_1000.
Tables 17 and 18 su1T111arize the anti-HBs status of recombinant and plasma-derived
vaccine recipients at 12 months. The GMTs of responders at 12 months are 2 to
5- fold lower than those observed at 7/8 months . However, when tallied across
00014
all age groups, 90~ of the 1"ecombinant vaccinees and 92% of the recipients of
plasma-derived vaccine retained fully protective titers (mIU/ml >10) at 12
months (Table 18}. Sixty-fhre percent of the recombinant vaccine reclpients had
titers of mIU/ml >100 at 12 months, while 25% still had titers of mIU/ ml >1000.
Among vaccinees who receive:d the plasma-derived vaccine, 70% had titers of
mlU/ml~lOO at 12 months, while 37% retained titers of mIU/ ml I l000.
Table 19 shows the frequencies of local injection site complaints, any type of
clinical complaint, and elevated temperatures reported by health care personnel
and other healthy adu l ts following vaccination with the yeast recombinant
hepatitis B vaccine in current studies compared with the frequencies of such
complaints among s imilar subjects in earl ier studies of plasma-derived hepatitis
8 vaccine. With either vaccine, the frequencies of complaints were somewhat
lower fol l owing the second and third injections. Over all injections, the fre-
quencies of inject ion site complaints and any type of complaint were 12% and
20%, respectively for plasma-derived vaccine, while the use of recombinant
vaccine was followed by reports of injection site complaint or any type of
complaint with frequencies ,o f 17% and 27%, respectively. All complaints were
mild, transient in nature and consisted most frequently of injection site
soreness. fatigue/ weakness and headache. The frequency of elevated temperature
(>lOOcF, oral) reported by healthy adults during a 5 day period following
vaccination was approximately 3%, both for recipients of plasma-derived vaccine
and of yea st recombinant vaccine (Tab le 19}.
Clinical studies with the recombi nant vaccine demonstrate its safety and
irrrnunogenicity. A comparison with histori ca l data obta i ned using plasma-derived
hepatitis B vaccine shows that 10 mcg doses of the recombinant vaccine and 20
mcg doses of the plasma-derived vaccine yield similar seroconversion rates and
GMTs in healthy adult recipients. Using historical data from past studies
involving the plasma-der i ved vaccine, clinical reactions appear to be somewhat
more frequent fo l l owing injEiction of the recombinant vaccine as compared to the
plasma-derived vaccine. However, in one contemporary double-blind study
involving both vacc i nes, clinical complaints were more frequent among recipients
of the plasma-derived as compared to the recombinant vaccine . Both vaccines
were well tolerated wi th postvaccination reacti ons being of a mild and transient
nature.
fable l
Clinical Studlts of Health Cart Ptrsonne1 and Othtr Htalthy Adults Rectlvlng Ytast AtcOllblnant Htpatltts 8 Vacclnt
Produced By tht (b) (4) Ntthod (88 IND 1925)
I Subjtcts
Oah Vue lne P l anned ~ with ant I - HIS Tl111t
Pop11 \at Ion Sl 11dv I Invest lg.tor location Initiated Sla \us lot Dost hgl111en (Vacclnlted) S/ N ~2 . l a)U/111 ~ 10 ("onths )
Htalthy 119-t • Bishop l'ltrck , Co • • PA ll/l&/ 83 In p r ogress ( - 1(444 10 IICf 0 , I, 6 IIOS. 30 (26) 100 ( 11/11) 94 ( 16/1 1) 1/8
Adults
Hulthy 909 -1 Plotkin, Phi ladtlpllla 6/19/84 I n progress C-1444 10 IIC') 0,\,6ms . 20 (18) 100 ( 11/11) 100 (\1/11 ) J/8
Adults Starr
Hultlly 839 8hhop llltrck , Co . • PA 7/31/84 In progru s C-1:444 10 IIC9 Day 0 10 ( st 2S ( l /4) 0 (0/4) 6
Adulh
Hulthy 181 1 lno Japan 12/84 In progr ess C- l21S 10 lat!I 0 , 1,6 IIOS . so (40) 100 (40/40 ) HA
Adults
Htalthy 894 Poll:: 8altl110rt 4/85 In progress C- ltS63 10 11C9 O, l,6 ac,s. (81) NA NA
Adult s 3S0
(Kale H- 8 - Vu 20 kg 0,1,6 91>S. (88) NA II.A
Ho.osexua Is) C- N252
Hea ltlly 898 lhhop lltrck l Co ., PA l l/18/85 In progrtss C-1112S 20 acg 0, 1,6 ac,s. 20 (2) NA lfA
Adults C--1'126 10 1Kg 0,1,6 _,L 20 ( l) NA NA
Hultlly 901 llno Japan 5/7/85 In p r ogrtss C- lll S 10 11e9/11'1 0,1 , 6 91>S . 62 (62) 98 (S4/SS) NA
Adults 10 IICg/SC 0, l, 6 ac,s . 62 ('2) 97 (56/S8) NA
Hu lthy 904 lttssler Chlugo 10/85 In pr09ress C- N111 10 IICg o.,., •s. 50 (SO) NA ltA
Adults C-Ul 1 10 acg 0.1., •s. 50 (SO) NA NA
Healthy 900 Zucktn111n Loodon, I)( 8/85 In pr09rtss C-fll 2fl 10 IIC9 O, l ,6aos . zoo ( NA HA
AdulU
(Ma le
ttc.c, S fl H ls )
Hei 1th hrt 792-1 Dttnsteg 8oston S/84 fn progrtss C- lS64 10 IIC!I 0, 1, 6 IIOS . 30 (JS) 96 ( ll/28) 93 ( 26/28) 9
Personnel
Heal th Cart 194 Alter htMsd1 4/18/84 In progress c-uo 10 acg 0,1 ,6 aos . 30 (41) 97 (3S/3') 94 (34/36)-- 1/8
Personntl
0
NA • Not AYal lable 0
•Suffh nullbu l ndtutn addrnd1a to Ini tial study protocol.
••lh1s ~runhge h \hat w1th S/11 ~10 , rather than •lUl•I ~10 .
....
0
IJ1
31531 / 1
l/9/86
Table l fCont.)
Clinical Studies of Health Cart Ptrsonntl and Other Healthy Adults Receiving Yust RecOllblnant H~atltls 8 Vaccine
Produced By the (b)(4) llethod (88 IND l92S)
I Subjrcts
Date 'lace lne Plannrd ~ with aiitl-H8s Thw
Pop11 lat Ion Study I Investigator Loc1tlon In It lattd St•tus lot Dost Aegl•n C V•cc lnttfd) S/N ~2.1 ■IU/111 ~10 (Months)
Hu 1th Cart 194-1 Alt tr Brthesd1 6/84 In progress C- K444 5 •9 0,1,6 ■os. JO (30) 84 ( 2 l/2S) 16 (19/25) .. l/8
Perso,mrl
Health Cir, 195- 2 Deinhardt W. 6er1111ny 12/1/84 In progress C-l215 10 •g 0,1,6.os . 300 ( 9 1) gg ( 19/80) 99 (19/80) l/8
Personntl C- KS64 10 •g 0,1,6 ■os . (148) 100 (16/76) 100 (16/7f,) 7/8
HHlth Cart l98 Hol Hnger Houston 4/11/84 In progress C-ll446 20 ■cg 0.1,6 ■os. 35 (36) 100 (JS/JS) 4.11 (32/35) 7/8
Personnt 1 10 ■cg 0,1,6 .OS . JS (31) 91 (34/35) en (35/36) 1/8
s ■cg 0,1,6 ■os. 35 (36) 91 ( 35/36) 83 (30/36) 7/8
ltulth Carr 801 Septla,s Houston 2/16/84 In progress C- K4« 10 ■cg 0,1,6aos . 25 (22) 100 (21121 l 100 (21/21) 7/8
PeNonntl
Hulth Car, 803 Juchon Otnver l /16/84 In progress C- U44 10 IIC9 0,1,6 aos. 30 (31) 85 ( 12126) es (2U26) 1/8
Ptrsonntl
Hulth cu·, BOl Schal■ Netherlands 4/4/84 In progreu C..«444 10 acg 0,1,6 ■os. 30 (31) 100 ()till) 100 (ll/31) l/8
Personnt I H-8 Vu 20 IICg 0,l,6 ■os . lO (25) 100 (ll/22) 100 (22/22) 1/8
1 S10J
K«alth Cart 808 SUil)l 1ner Tucso• 4/3/84 In progress C-U44 10 •9 0,1,f, MOS. 25 (25) 9' (22/23) 96 1nnJ) 1/8
Personnrl
Health Carr
Personnrl
811 ,rob Switzerland 4/10/84 In progrtss C-K446 10 •CJ 0, I.• aos. 11 Ill) 86 Oil) 93u•15/6) 7/8
Hu Ith Cart 813 tavldson IITC 2/1/84 In progress C-U44 10 acg 0,1,6 ■os . so (62) 97 (38/39} 91 (38/39) l/8
Personnel
Hulth Care 813 - l D4Yldson •re 2/84 In progrns C- K444 5 IIC9 0,1.6-,s. SO (Ml) 94 ( 44/4 7) 91 (43/U) 7/8
P•rsonMI
Hu 1th Care 113-2 Davidson NYC S/84 In progress C- K444 2. 5 ■cg 0.1,6 ■os . 50 (61) 100 ( COl'O) 9l (39/40) 7/8
Personntl
Htl Ith Care 813- 3 Cavldson NYC I/IS In pn11rns C- l220 10 .cg 0,1,6aos . 50 (62) ,s (31/39) 92 (36/39) 6
Personnel
He• Ith C.re 813-4 Cavldson NYC 2/1S In progress C-l220 S •9 O, l ,6 aos . so (61) 93 (41/44) 80 ( 3S/44) 6
Personnel 0
0
0
••rhls percentage ts that with SIN ~10. r,ther tMn ■ IU/■l ~10 .
O'-
•••sastd on 6 subjects (S responders) for wh- n-rlc tHrrs ,r, av1Hable.
llSll/l
1/1/96
Table l (Cont.)
Clinical Stud1fS of Htilth Care P•rsonn•l and Other Healthy Adults Recelvtng Yust RrcOllblnant Hepatitis 8 Y1cclne
Produced By the {b) (4) ~thod (88 IND 1925)
I Subjects
Oah Y,cc1ne Planned ~ wlth antl-HBs Tl111e
Popula t ton Study I Investigator location lnlt I.sled Status lot Pose Regt,wn (V,cclnahd) S/N ~2.1 ■IU/■t ~10 (Months)
Hu Ith Care 813- 5 Davidson NYC 6/85 Jn progress C-11125 20 ■cg 0,1,6 .,s , so (1) NA NA
Personnrl C-fll26 10 ■cg 0, 1,6 ■os . so (J) NA NA
He, 1th Carr 816 Plott In , Plll11delpllta S/IS/84 In progress C-U46 10 •9 0, 1,6 -,s . 25 ( 8) 80 (4/5) 80 (4/5) 1/8
Personn, 1 SUrr
Hulth Care 835 lffllOn Ch1pe 1 HIii 10/26/84 In progrus C- l564 10 •9 o. 1,6 -,5 _ 30 (29) 100 ( 19/19) 100 (19/19) 1-9
Personne 1
Hu Ith Care 838 Deinhardt W. Gen1111ny 6/1/84 In progreu C- UJ3 10 ,acg 0, I ,6 ■os . 2S ( 21) 94 {Hi/11) 94 { 16/11) 118
Ptrsonn, 1
Hta 1th Care 859 Clunieclr. Bflgl• 3/12/85 In progrn s C-l563 10 •9 O,l,6 ■os. so (31) 80 (24/30) SJ (16/30) 3
PtrsOflne I
Hea ltfl Care 860 L1ufs W. Genuny 12/28/84 In progres s C- K563 10 •g 0, 1, 6 ■os . 100 (60) 100 (S6/S6) 100 (56/56) 1/8
P,rsonne I
Htalth tare SU llanlt\n, tanada 5/85 In progress C- L2l7 10 •9 0,1,6 -,5 _ I SO (11) 32 ( 22/68) 12 (8/68)
Ptnonnel Coates
Health Cut 8ll Oon S\ngapore 1 /l6/85 In progress C- J.51>4 10 ia:g O, 1, 6 ■os . 30 ( 31) 91 (28/29) 91 (21/29) 7/8
Ptrsonnel
HHlth C~re 880 Worwsrr va111alla, Nf 4/l /85 In s,rogn!>S C-l21S 10 .:g 0, 1 ,6 ■os. 50 (50) 86 (31/36) r,4 ( 23/36) f,
Ptrs1M1nr I C- L216 50 (43) 100 120/20) 100 (20/20) r,
C-l21l 50 ( S4) 18 (23/26) 81 (21/26) 6
C- L2'9 50 (0) 90 ( 19/21) 81 (\1121) r,
C-l220 SO (43) 91 (38/39) 90 (JS/39) r,
Hta ltll Cue 883 Plott In, Phlladelphl1 11/13/84 In progress C-L220 10 ■cg 0, I .6 ■os. 25 ( 28) 100 (l4/24) 96 ( 23/2◄) 1/8
Prnoenel Starr s ■cg 0, I ,r, ■os. 25 (25) 100 (20/20) 95 ( 19/20) 1/8
HealO C,re 885 Liebowitz IH1at 1/IS h progress C-l2lS 10 •g 0, 1,6 IIOS . 50 NA NA
Ptrs011ne I C- l21' 50 11A 11A
C-l21J 50 ( 50) NA ICA
C-L219 50 (50) NA NA
C- l220 so (50) 11A NA
0
Hnlth C1~ 889 Perl I lo St. Louis 6/19/85 In progress C-K'37 10 IIC9 0,1,6 ■os . 50 (88) 11 (14/82) 6 (5/82) 0
Per\onnel
Ilea 1th C1re

Personnel
83 ◄ Rtzutto lhly 8/8S In progress C-KS6-4 10 •9 o. 1,6 .,s . 30 (25) NA NA
-
0
~ '
fable 1 (Cont.)
Cl ln\cal Stud\e~ of Ht•lth c,re Personnel and Other Healthy Adults Recttfln9 Yeast Recombinant Hepatitis 8 vaccine
Produced By tht (b) (4) Nl!thod (88 UID 1'2S)
I Subjects
Dlte Vaccine Pl,nned I!; with ant t - HBs n-
Populat Ion Study I Invest ll;iator Location lntt lated Status lot Dose Rtglaen (Yacc lnahd} S/11 ~2.1 •IU/■1 ~10 (llonths)
He. l th t,r, 841 Zuchl'llln Uni led Klngd011 S/85 In progress C-l563 10 ■cg 0, I , ' IIOS . 100 MA NA
hrsonnel
Hulth c,r, 891 Hu ChlM 12/8S In progrus C- KS•4 10 ac:g 0, 1,6 IIOS. 100 (2S) NA 11A
Personnel H-8-Vax 20 ac:9 0, 1,6 IIOS . 1DO (25) NA 11A
0027l
Ht1Hh C1re 912 Sh1 ■tzu J•pu 9/UBS In progress C-l220 10 111C9/IN 0,l,6110S . 87 ( 87) 7S (S6/1S) 11A 2
Personnel 10 •9/SC 0,1,6 aos . 88 (88) s, {0173) NA 2
IIHllll Can 914 Bur·tttt high• 11121/85 h progrus C-fll26 10 •9 0,l,6110S . 20 (20) NA llA
Personnel
Ht1lth C1rt BIS Sch1I ■ Netherlands 12/85 In progress C- 1(937 10 •9 0,1,6 aos . 30 NA 11A
Personnel 20 •9 0,1,6 aos . JO NA NA
H-8-VAX 20 •CJ 0,1,6aos . 30 NA NA
2271l
Kea Ith C1re 861 Crovarl Italy Planned C- l564 10 •g O.l.6110s . 30 MA ICA
P«rsonnel
He•ltll C1re 899 Ot!Uc Jhly Planntd C- l564 10 ac:g 0,1,6 ■os . 30 NA NA
Persot1nel
C>
0
31531/4
1/8/86
-
C>
OD
Cl lnlc•l Studies of He110phll1•cs . Th•l•sst■ 1c Children and Patients With Slcklt Ctll Ant■ la
Rtcth1ng Vtu t RtcOllblnant Htp.t It Is B Yacclnt Produced by tht (b) (4) Ntthocl ( 88 IND 1925)
I Subjects
O•te Vacclnt Planned with ant1 - HB fl•
Popuh t Ion Study I Investigator lontlon 1nlt1attd s utus lot Dost Rtg1Mn (V,cclnattd) SIN ~2 . 1 ■ IU/■ l ~10 (Months )
HttaOPh I 1 l,c s 861 GIi l NI l w.ukte 11/8/84 Ill progress C- KS64 10 •9 0.1.6 IIOL 2 ( 3) 100 ( 2/2) 0 (0/2) 3
S IICg 0 . 1.6 aos. ZS (12) 100 (8/8) 100 (8/ 8 ) J
Jh• l11 SHIC 799 Stuens NYC 9/4/84 In progress C- 1:444 S IIC9 0,1,6 aos . 25 (l S) 89 (1/9) 78 (1/9 ) 1/8
Ch i ld r tn 2 . S acg 0 , J , 6 IIIOS • 2S ( 16) 82 (9/1 1) 64 C1/1 I ) 6
Pat ltr,ts 861- 1 Gill NI lwauktt 1/85 rn progress C-ICS64 5 IIC'il 0 ,1 ,6 -,s . 10 (4) NA NA
vltll Slctlt
Ce 11 A11ttth
,,.
J ISJI/S 0
l /1/86 0
0
l•bh l
Cllnlc•1 Studies of He1ltby TeeMgers, Children •nd lnf1nts Receiving Ye1st Recoabln•nt
Hep•tltis 8 V•cclne Produced by the (b) (4) Meth9d (88 IMO 1925)
I Subjects
Date Vaccine Pl•nned ~ vlth antHl!s lt•
Popu lation St1idy I Inv es tl91 tor Locat Ion Initiated St1tus Lot Dose llegl•n ( Vue lnated) S/N ~2 . 1 ■ IU/■1 ~l0 (llonths)
Hulthy 81'l Papaev109e lou Gruce 5/12/84 In progress C--Jt564 10 ■cg 0,l,6 aos . 5S ( 55) 100 (52/52) 100 (52/52) 1/8
lun1gers C-K732 5 ■c9 0. 1.6 aos . 55 ( 55) I 00 ( 54/54) 100 (54/54) 118
C-l732 2. 5 ■cg 0, I ,6 aos . 55 ( 55) 100 (53/53) 94 (50/53) 7/8
Healthy 80'.I Plott 111, Pht lade lpllh1 2/2/84 In progress C-U44 5 ■cg 0,1,6 aos . 20 (22) 100 (14/14) 100 (14/14) 7/8
Chi 1'ren St1rr 2 . 5 ■cg 0,1,6 IIOS. 20 ( 11) 100 (10110) lOO (10/10) 1/8
809- 2 Plott la, Ph I lade \pl\\• V19/84 ln progress C-1032 2 . 5 ■cg 0,l,li aos. lS (15) 100 (H/11) 100 (11/11) 1/8
Starr 1 .2s acg 0, 1,li aos . 25 ( 26) 100 (14/14) 100 (14/14) 7/8
Healthy 865 Yeoh Hong Kong 2/1/85 In progress C-U3-4 s ■cg 0,l aos. 100 (90) 96 (23/2-4) 88 (21/24) 8
Chi 1'ren/ S acg 0,1,6 aos. 100 (81) 100 (21/2\) 100 (21/21) 8
lnfa•ts
Hulthy 891 Hu China 12/BS In progrus (-1(564 s ■cg 0,1,6 ■os. 100 (25) NA lfA
Chi l4ren H-1 Vax 10 . , 0,1,6 ■os. 100 (ZS) NA 11A
002ll
Hulthy 843 Oon Sl119apore Planned (-f,;}34 s ■cg 0,1,6aos. 30 MA NA

Chi Uren C-fl127 2 .5 IIC9 0,1,6ms. 30 NA 11A
C-fll 28 1 . 25 w:g 0, 1,6 ms. 30 NA NA
C-fll29 0.6 ■cg 0,1,6IIOS. 30 NA lfA
0
0
0
IV
0
31531/6
1/11/llf.
Tall le l
Cllntcal Sludlu of Ol•lys ts/Pr«tatuts PUhnts and Mentally Retarded Patients bcr1v1ng
Yeast Rec011t>t11ant
Hepat lt •s 8 l ee"'' Pro:flced by the (b) (4) Mettioc! (88 IND 1925)
I Poputat ton
Dialysis
Study I Invest 191tor
816
Loutlon
01te
Initiates itstus \..~t
Vue Int
11ose Reg1•n
I Subjects
Planned
(Vacc111at~)
I v1th ant HIiis
S/N ~2. l •JU/■ l ~10
Thw
(Months I
Pl oUtn, PMl.tdelp/11 ■
Pat 1ents 5/lS/84 l~r~s C-«446
Starr 40 lltg 0,1,6ms . 25 ( 361 80 ( 16/20) 75 (I S/20) l/8
20 lltg 0, l ,6 an. 2S ( 39) 51 ( H,/28) 46 ( 13/lB) l/8
Ol.i1lysls 838 o,tnhardt
Pat lents II. ~f'llllly 6/}/84 I rpr::>9Tt ls C- lt73J 40 lltg 0 , 1,6 ms . 50 (SI) 64 (23/36) 58 (21/36) 118
Dialysis 838 -1
Pat lents Oelnh1rdt w. ~n1uy 11/84 h:~n)ire<.s C- (133 40 11<9 0,1,2,3,4, 20 (20) 61 (l0/15) 60 (9/15) 10
fl IIOS .
20 acg 0,1,2,3,4, 20 (20) so (9/18) 44 (8/11!) 10
Otal~ t s fl aos .
82S Alter
P•tlents Washington 4/10/85 l11nQiress C--l915 100 acg 0,1,6 IIOS. 30 ( 44) 68 (19/28) 2S (l/l&)• 3
Pred11lysh 789 Hael ltori Ourh•
Pitlents S/23/84 l crogre-ss t--«<446 40 IICg 0,l,6110s 20 (15) 71 (Sil) 57 (4/1)* 7/8
20 a:g 0,1,6 -s . 20 ( 14) 8' (6/7) Sl (4/1)* 1/8
Preu 1a lys 1s 811 Grob
H-1 Yu 40 IIC9 0, 1., aos . 20 (If>) ,1 (41') 67 (4/6)* 7/8
P1tle1ts !wtturl,nct <4/10/M I prc1rt-n c-c•u 40 l!IICg 0,1,6aos. 20 (13) 64 (1111) 64 (1/11) 7/8
20 acg 0,1,6.os. 20 ( 14) SB (J/12) S8 (J/12) 1/8
lO IICg 0,1,6iaos . 20 C14) IS (2/13) U (2/13) 1/8
11-8 Yu <40 acg 0,1,6 ■IOS . 20 (11) 50 (4/8) 38 (3/8) 1/8
20 acg 0,1,6 -S . 20 (ll) 25 (2/8) 25 (218) 1/8
Pred fa ly s Is 838-3
P•t l fflts
Ot-lnhudt W. 6e,_11y 1/IIS J progress C- k733 40 acg 0,1 ,6 a)S. 10 ( 8) 13 (1/8} 0 (0/11)
Nent,1 ly 889 Purl\ lo St. louh
Rt-hrdt<t 6/1'1115 pr~ss C- k931 20 IICg 0,1,6 .as . 125 (101) 20 (Z0/100) 11 (11/100)
llrnt, lly 10 IICCJ 0,1,.6 aos . 125 (101) 19 (19/101) 8 (8/101)
81S Scha I•
bhnlrd Nettlerl1114s 12/95 } llrog~s~ C-lt937 10 . , 0,1,6 aos . 30 NA NA
20 ~,·
o, 1,,, aos . 30 MA NA
N- 8-ru 20 . 0 , 1 ,6 .as . 30 NA NA
22711(
0
0
0
"lhh Pt-rcenhgt-
Is that wtth S/~10, rather tti.n •lU/■l ~10 . -
rv
Table l
Clinical Studies of Ho~responders and Hyporesponders, Chronic Carriers of KBsAg, and Preill'llllln; 1925 )
AdtAlts Receiving leas\ Recflllblnant ttepat1t1s 8 vacc\ne Produced by the (b)(4) Method (8B IN
f Subjects J with antl - HBs T\lllt

vaccine Planned {Months)
Date
Study I Investigator Lot Dose Regl111en {Vaccinated)
Population location ln\t 1ated Status
63 (5/8) 7/9
10 (11) 88 ( 7/8) 7/8
Nonresponders 794 -2 ~lter Bethesda 6/84 In prog~ess C - ~4~ ◄ 10 111Cg 0, l ,Ea IIOS . 0 (0/1)
(1) 100 ( 1 /1)
to Plas.a 5 IIICCJ 0, 1 .6 IIOS.
Vaccine
(Healthy Aclults)
33 (1/3) l/8
4 (4) 33 (l/3) 3
Noru·es1>onders 8H, Plott. In, Phi ladelphh 5/H/84 ln progress C-K44b 40 nicg 0,l,6 IIOS . 25 (l/4) ZS (l/4)
0, 1,6 IIOS 5 ( 5)
to Plas111a. Starr 20 • 9
Vaccine
(Oh lys ts
Pat lents)
0 (0/2) 1/6
20 ( 4) 0 (0/2)
Honrespondtrs 811 Bishop Merck & Co., PA 3/21 /84 0 , l .& ll05.
to PlasN
Yacc lne
(Healthy Adults) t,
SB (1/12) 25 ( 3/12)
Honr,spondtrs BS ◄ Olenstag Boston 10/4'/84 In progress c-ist.4 10 .cg o. l ,& IIIOS . 20 (14)
to Plassa
Yacc lne
{Healthy Adults)
15 (2/13) 2
0, l,f, 20 (l 1) 38 ( 5/13) 2
Honrtspondtrs 875 Johnson Duluth 7/85 ln .progress t-(937 40 w:g 11105 -
47 (1/15) 47 (7/H)
40 .cg 0,1,6 IIIOS , 20 (18)
to Plas1111 K-B Vu
V.ricclne
(ti1alysls
Pat hnts)
M~ 50 (112)
10 111(;9 Day 0 20 \ 2)
Hyporesponders 854 Otenstag Boston 10/4/94 In progress C-IC.56'4
to P1as11W1
Vaccine
0 (O/18) 0 0 (0/18)""')
10 0,1,2,3.4, 15 (111)
Ctirontc 8S◄ Olenstag Boston l 0/4/84 ln progress C~S64 IICCj
cerrien of 5 ans.
HBsAg
11 0
ulhls percentage (proportion) refers to the nuniber o·f chronic carriers wtio beca111e seronegatlve fClr HBiAg after accinal1on 0
whh recOllb\nant vacc1ne . 0
N
3 1531/8 l'\J
l /8/8b
Table 1 (Cont . )
C Hn1ca 1 Studies of Non responders ar,d Hyporesponders, Chronic Carriers of _HBsAq, arid Prein1111ne l9Z!i)
Adults Receiving Yeast RecOllllbln1nt.Hepatltl\ 8 Vaccine Produced b~ the • -- (b).,. (4).. Method (88 IMO
.,
I Subjects T\me
~ with anti - HBS - l"ontM)
vaccl Ile Planned SIM ~2 . l •1U/~1 ~10
Oate ("acc1nated)
Populat 1on Study I lnvesttgator location ln1t\ated Status lot Oo\e Qeg,1111en
f, 1 (2/3)
1ra11s hnt 854 Oien stag Boston 10/4/84 ln progress C-K5M 10 IIIC9 Day 0 n (3) M.l
lt~sponders 'l
NA
Non - 874 Tong Ca 11fornla 9/85 In pro9Nits C-IC.563 10 IIIC9 0, l ,f> MOS . •o (26) 36 (9/25)
responders/
Hypo-
responders
Prel11n11ne 813-f, Davi,dscn NYC 7/85 Ill prog,re-!.s C--f4l 26 10 IK9 Day 0 100 (31} 97 ( 29/30)*
IIA
'
~dulls l/2
tOO (ZB/28)" , n.
Prel-ne 813 - 7 Davidson NYC 1/85 Ill proiiress C--fll26 5 atlj Day 0 2S (28) 14,\
MA
,oc (26/28) *
10 W:i Ot'Y 0 2, ( 28)
Adults 1/8
100 (5/S)* 100 (5/!i)
20 (S)
Prel-ne 817 Bhhop Merck lo Co . J/ll/84 111 J)rogress c-u•• 10 acg tllY 0
Adults
*lhis percentage (proportion) refers to the n\llllber of pre1-..ne subjects ◄ naturally acquired or ~a,c\ne- 1nduced, ~s
1nd1
cated) 0
who exh1b1ted a boost 1n antl -HBi titer after rece1v1n9 rec011b1nant ~•cc1ne. 0
0
N
\.,,I
HSll/9
1/8/96
Table l
Clinlcal Studies of Neonates Born to Carrier llothers Receiving Yeast Reconlbinant
Hepatitis 8 Vaccine Produced by the (b) (4) "ethod (88 IND 1925)
# Subjects
/>opolat Ion Date Vaccine Planned ~ with ant1-HBs T111e
Study I Investigator Loc1t1on Initiated Status lot Dose Aeg111en (Vaccinated) SIH ~2 . 1 tllU/111 ~10 (Months)
Neonates of 864 Stevens NYC/LA/Sf 9/1/84 In prog•r ess

H8eAg ► C-U32 S l!IC9 0, 1,6 IIOS. 80 ( 134) 100 (47/47) NA E,
Methe rs + 0.5 .,
HBl6 at
b1rth
Neonates of ' Yeoh Hong J.on9 2/85
H8eA91
"ethers
(!~~ In progress C- J.734 5 IIIC9 0,1,6 IIOS. 150 (40) HA 100 {24/24) 3
., \ +- 0. S •1
NBIG at
birth
H--11 Vu 10 IIIC'J 0, 1,6 ■os . 75 (28) NA 100 (19/19) 3
1032K. + 0.5 Ill
24SSJ HBIG at
0027L birth
1507J
Heonates of 878 Sun China
HlleAs,+ uas ln progress C-KS64 s acv 0, 1,& aos. 30 (30) NA HA
i.others i-0.5 ••
H816 at
b1rth
Planned C- l564 5 IIICg
r::-_
0, 1,6
-~~IIOS. 70
~ o HGIB) J
Neonates of 892 Hu China 12/65 In Progress C-lS64 NA
H8eAg ► 5 IICg 0,1,6 IIOS. 50 (S) NA
Mothers 10 acg 0•,l,i 50 ( S) NA
, -------, .,)
H-8 Yu
0027l
10 •g
20 acg
0,),f,
0,1,6
IIOS.
taOS .
IIOS.
50 (5)
50 (5)
""
NA
NA
NA
NA
Neonates o f ~, , Yfoh Hons, Kong
N!ldg - 2/6S In progress C- K734 5 IICQ o. 1 .6 .as. (75) NA 100 (41/41) 3
~~
"°thfrs ~ e. J1' ,
; I
+ 0.5 111
H816 at
birth
- H-8-\IAX
10321
2455J
10 acg 0,1.6 aos.
+ 0.5 .,
H816 at
{85) NA 100 {42/42) 3
0027L birth
150lJ
0
C)
0
rv
s:::
Jl531/10
noo2s
Table 2
List of Number Vaccinated with
Yeast Recombinant Hepatitis B Vaccine, Clinical Reports, and
Post-Vaccination Antl-HBs Data by Population Group
NA= Not Applicable

Vaccinations Clinical Re~orts Anti-HBs Data
Injection t. Injection I. Injection
Population Group _1___
2 ___
3_ _ 1 ___
2 ___
3_ _1___
2 ___
3_
Health Care Personnel/Other 2414 2286 1442 1626 1508 990 1616 1436 1048
Healthy Adults
Healthy Teenagers 165 165 165 165 165 165 165 165 165
Healthy Infants/Children 258 222 122 220 191 100 213 189 97
Dialysis/Predialysis Patients 288 287 196 286 264 184 258 230 166
Mentally Retarded Insti - 202 201 200 202 201 202
tutionalized Patients
Thalassemic Children 31 31 27 30 30 5 31 27 14
Hemophiliacs 15 15 6 13 10 6 15 15 6
Patients with Sickle 4 4
Ce 11 Anemia
Nonresponders to Plasma-
Derived Vaccine
Healthy Adults 55 54 24 30 28 24 52 25 14
Dialysis Patients 26 24 6 25 24 6 20 21 4
Hyporesponders/Transient 5 NA NA 5 NA NA 4 NA NA
Responders to Plasma-
Derived Vaccine
Pre1rmlune Adults 91 NA NA 48 NA NA 88 HA NA
Chronic Carriers of H8sAg 18 18 18 18 18 18 18 18 18
Infants of Carrier Mothers

HBsAg+/HBeAg+ 214 157 73 135 114 43 133 110 19
HBsAg+/HBeAg- 75 73 30 75 73 30 70 41
T OT Al 3861 3537 2309 2878 2626 1571 2885 2277 1551
wva-31651-1 - 1/10/86
T11blP 3
Anti bod)• Responaff at J Hcnths An,n11 lie dl.•J
IoJtl~lly Serone~•t l v. Per&ona Receiving YPast Recoablnant
Hepatltls 8 Vaccine 111 0,1 and 6 Hontha
l,~ai:1 2 5.,.
_j vtth lllltl --'tls s -=s )2!!!g! 20 ■c<I
QIIT '1!JW.lj•
I
I v 1tll Mtf-Ni 11111 11 11/al] T ~ •iltl Mti -'9s Qlt (alUlall* ~ 11ith Anti ~ an ~•u.ran• I v i tb ,. l I . - Oil IIOIUlall *
..... I I I
(Y'Mn) VIS!l. 1
■Ill/al
? 10
I
I S~2 1/
alUl■I
!:: 10 ~ l .1
IIIU/91
?. Ji, Sll?_l . 1
aJWIII
!:: 10 l~l.1 ■IUl■l
!:: 10 SIN!::2 I
■JIJIIII
!:: 10
I
S/11>2. 1
l.l\_t/al
!:: 10 S~2. I
I..iw■,
!:: 10 SJll!::2 .l
IIIU/al
!:: 10 S~2 I
■IUl■l
?_ IC
l -11 IOO
(Ill) •
("'' I Sl I 11 .S 100 81
(Ii/It) (13/lil
11 3 llO. S 100
(10/10)
im
0 01101
18'. 3 l89. 3
12- 19
(.,~,
ti ~I 31.1 r,3 3 100 94 l07. 9 IU 4 100 100 189. 2 21S.4 I'
20--1'9 ..
(4JISI)
(Jl/!,4)
n
(331511
37 . 6 '6,, l
(WS4)
83
( 1181141)
(S Ii!>')
'1
(95./1"21
3,1 [) SI . S
()lo~)
tl
(SU'56)
83
(3St/JIB) (3l3/JIIB
61.<J "8.'t M
(16/19)
!,II
(11119)
lf S
"·'
»-3'
100 ~ u 12 I so 31 18 . ., 18 ,1 38.1 10. 1 ,. 56 , .s
"·'
.,.., W4J (1/41 161 ") (Sil') (81'112) ( a-'111) (l!>/16) (1116)
- 12'. 8
so..s,
"
(2111
0
(013)
3. 6 IS
(?la8)
~
( IS/26)
4 1.9
100
( 111 1
100
(111 1
n ., 13. , 81 ,s 21., 31.3
(14 /11 ) (11/11)
'°4t
IS Z!, s., 24 2
(314) (1/4 )
~ a n l y.
24101/1
l2/2'IJas
0
0
0
N
c>-
hbl e 4
Ml 1body Ruponses at 6 Mont hs lulong ~ealchy lnlL i ally S.,r one ga live Perso ns
Rec e i v ing Te~• Recoabl nant Hepat i t is B Vaccl nr at O, I , and 6 ltonths
I wltll ~nt I- Has

I :>• -..
~ I l ■ IU/■ H• I wU!! ,
Antl - Hh
1. S acg
" " (a1u1■11•
I
I with Ant 1- H8s

s ...
I
&MT l•IU/ •l l. 'S
IOc•
w1ll• Mti..fes
1I willl Mli-ffh20 «1 ~ I laltv.tl•
-
Agr
( THr~) S/N?_2 1
11IU/■ I
?. 10 S/k?_2 . I
■ IU/■ l
?. 10 S/~2 . 1
i ■ IU/■1
?. 10 S/ N?,2 I
I■IU/al
?. 10 SfN?.2 . 1
■IU/ml
?. 10 5/N?_2 . I
, •IUl■I
?. 10 ~ 1. 1
aJlllal
?. 10
~• '· ; : 11
~11 ?. 10 ~ 2. 1 1
aiW.I
? 10 SiJ1!2 I
' •IU/>111
? 10
- I
I
I · 11 100 90 75 . 9 100. l 96 9) l4S . 2 163 . 2 100 100 308. 4 308.

(21/211 (11/21) (2.✓ 2l) (2S/21) ( 19/19) I 19/19)
1l - 19 9◄ 71 I
Jl.3 59.4 100 100 107 . S 107 .s 100 !19 161. t 16,. l
(.\1/Sl) (36/51) (54/ ~) ( 54/54) 041)4) (Jl/74)
33 . 4 Sl . 4 ·' 88 1l 43. l 1 1. 2 9' ,0

• •• IIS 8 ,a ,, <,e I 8'1
20- 29 8'
(4S/S2) ( 36/SZ )" ( l2S/H2 ( 102/142 («IY41, (ll'Jl41t (11/ 19)
,,
(l~ltl
30 · 19 H 15 22 . 9 22 . 9 Cf, JI ll.4 22 .9 89 19 53. 4 10 1 14D lS I 34 . \

( 611 l I ( 4 /13 ) ' (I IC/124 (,a/l24) (lVIS) {12/15)
l 3f 4 l
...
(3/4)
40· 49 18 33 10.S JS . S 8l
(1011'1
,.
(lV34)
11 l
(213) ( 1/J)
50 S9 100
(1/1)
100
( 1/))
IS . S 15 . S II
(131111
100
.,
(1111'9
33
42. 4
13. 1
s,.
112 I
I
i
60 69 '
tun (1/31 ....
*lupolldtrs only.
2410( - 3
12/16/IS
C>
0
0
N
....,
Table 5
Anti body Responses at 7/8 Honths AmonEt Healthy

Initially Seronegative Persons Receiving Yeast Rec~mbinant
Hepatitis B Vaccine at 0 , 1, and 6 Months-
,.ii.-• ,_ 20ac•
.. ..,u. .........
I "'_..
-· ,_ w.:..... I. ,n . . . .,,_.... ... ,. hlAal l• I. ,.,H.i, • .,i .-. IIIT '- 1"""'11-.
11--
..-=i ...... • ,, .... CIIT ,.,, ,o.,ia ' wi th Anti-HI• CIII ' · II/all '
...
CY-.) ~l. l
'allllal
~ 10 SJW!Z . I
alW.l
~ 10 Vll?.2. I
.nu.,
? 10 Vll?.2. I
llliv-1
~ 10 ~ l. l
all.Ila!
? 10 ~ 2. 1
11111,,'a)
? 10 ~ 2. 1
atU/91
~ lO SJIS?2. I
eJUl'III
? IO ~Z . l
allV■I
~ 10 S/~ 2 I
■JU/■I
? 10
1-11 11• 100

(tl/11) (H/17)
ZCM.3 2Qff.J 100
(20/20)
too
tanoJ
sest .O ~ -0
,,.,it)
100 100
(MH4)
ISIM .O ~ -•
12-19 lOO
( ~ ) (WU)
M .... ] IIJl .8 lCIO
(WS,4) ,~,
100 ZSSJ.• fflJ . 4 100
(Wff)
IUO
(MIMI
1113. 4 2913.4
• • ,, 173'.0 100 84 !>21 3 1313 I
.., "
llS,.s
ZC,...lt 100
(~I (\2/S41
ZJI0.2 316. 1
,.,.> 94
(11UW)
423 . J
lMVl441 ( ~ ) " 110'-0
(Hilt) (1'1191
..... lCIO
(I/JI
100
(1/J)
211 .0 211.0 '2
(12/13)
!>4
0113)
IS. I
(MJWHI)
'5
(IOl5/lll)
m .s )300 100
"""'
M
(15./lil
~32 I~ I
...... • .s ., . ..s '6S.9

100
(3/J)
100
(3/l)
• .5
(U,J4) "
(3l/J4)
100 Zl.1 21.I to ,0 ~ .o t42.0

~~
180
(11119) (H/19)
(1/1) (Ill)
,i,.o
...... 180
(Jill
100
(3fl)
919.0
·--- ---- . -
. --··-
•l nclude .,_e ,~spon••• ■ea•ured at 9 aonthl when chat wa• the flr•t blood aa■ple obtained following the third lnjertion of vaccine.
5 5 0
0
0
rv
(lC
141 01 ')
1/11/a
Table 6
Antibody Responses at 12 Y.onths Amoni Healthy
Initial l y Seronegative Persons Receiving Yeast Recombinant
Hepatitis B Vaccin e at 0 , I, and 6 ~onths
1.: x - 2.S c:a s.:.. ,o ..... 10 - - I

\ with Ant\-Hts on ,_.,.,._11• ~ with h,f \--.. ""f '"'tllltll • '1 witll Anti~s CIII ' • tllltl I* t. wlO ._ IJII~ IJII ' • ' V.11" '1 wit.II AJ ti4'1~ QIT '••ut~-
I
•
(Y. .~1 ~ l.
111.U.l
!:, 10 ~2. 1
aJUlal
~ 10 ~ 2 .1
IIIW.I
~ 10 ~2 .1
IIIU/111
~ 10 ~2.l
alUl'al
~ 10 ~2.1
aflllal
!:. 10 ~ 2. 1
allVIII
~ 10 S~2 I
altllal
~ 10 5.1~2.I
all.ll■I
~ 10 S~2 . I
■ IU/■l
~ 10
I 1- 11 100 100 819. 2 819. 2 100 94 2llllU 392!) . 0 100 100 3481 .8 3481.8
(9/9) (9/ 9) ( 18/18) (11'18) (1311)) (13/131
12-11 '2
(49/S)J ,~,
91 1918. l !>4l. I IOO
~)
,oo
(WS4J
4!18.2 418.2 I«>
(55/SSI ,~,
100 wu. !,60.S
20-lt 9S 90
140142) (38142)
ue., 111 . , 96
01/80)
e,
(45/801
121. l zi..2
• 93
(115./118) OIQ/'118
342. J 419. 3 ~
( 18119)
8'C
(16/19>
Ml 449 3
ll)..)'t 100 n SJ. I 11,.6 64 18 J .9 U .4 94 8' 235.4 322. J 100 !ti

·~ 2
291 . 9
I
44141 (3/4) (l/11) (l/11) (}U,t) (68/1') (16/16) 1141'16)
I
Zlll. 3
~· IOO
(Z/2)
IOO
(212)
10.2 10.2 91
mm>
' tl
(21/n)
2311. l
so.-s, \00
11/1)
0
(Oil)
!..S -- •
(IS/II)
82
(14/111
150.'J 202.2
100 100 Z33.S 233. S

60--69 (212) (2/2)
~ O f t l y.
0
0
0
N
,D
21101/P
11/26/lr>
ooo:rn
Table 7
Pere entages of Ant11-H8s Specific for! and~ Oetern1inants of

HBsl~g in Post-Vaccination Sera
Time Numbe1r of S Anti-a % Ant1-d

(Months} ~l!.L Range Mean Range Mean
26 0-100 68 0- 100 31
3 97 33- 100 90 0-63 10
6 44 58-100 93 0-37 1
7/8 38 81-100 95 0-19 5
'
31751/1
1 /ll /86
Table 8
Adverse Exper iences to Yeast RecOlllbinant Hepatitis 8 ~occlne
lot of
lli!u Case I. 88-INO !fcc1ne 2ose
0ah1 Date of Datt Vaccine•
Adtl1n1strred Event lle2orted SW111111ry of Event lie lated
179 (b) (6) 1925 C- IC4H 10 IIICg (b) (6) {b) (6) 11/15/84 A forty-one year old fttaale developed headache, Yes
(b) (6) swollen face and rash within several hours after
(b) (6) rece1v1ng the third Injection of vaccine. Head -
ache and swollen face resolved In one day, and
the rHh faded over four days . llo cl lnlc.111 c0111t-
pl11nts wre reported by this Individual following
the f1r~t and second Injections of vaccine . She
received her first and second Injection of
vuclne es scheduled, while the third injection
was not ad ■ lnlstered until 11 110nths after the
flr~t injection . The Individual does have a
history of allergies .
789 1925 2449H 40 IICg (b) (6)
(HEPTAVAX ) I 0fl9/8,t This 30- y,ar old Mle subject had congtn1tal poly - No
(b) (6) cystic renal and liver dtsease . He had a h1story
of recurrent heaorrhaglng froa esophageal vartce~ .
He was ad■ ttted to hospital for he■orrhage of
esophageal var1ces . Oeath was due to subsequent
lnfect1on, 1MJltlsyste11 organ failure and shock .
189 1925 20 llltg (b) (6) f,/19185 f~1s 58-year o1d aale subject had a history of Unlltely
(OJ (ti) hypertension and chronic renal failure (pre -
dlalysls). He died at h - approxf,uttly 4
IIOflths after receiving his s,cond Injection of
vaccine. The Jnv . stated the patient was Jost
to fo110111- up. cawse of death Is unknown.
198
1925 10 IICg (b) (6) ll /19/84 A 32- year old .ale subject had an elevated ALT No
(b) (ti) level at the tt• of his 3rd Injection. On
(b) (o) (b) (6) the patient reported his urtne ,had
been dark orange 1n color for the prevlou~ 1- 8
days. The patient beca• anorexic and began to
v011lt . Jaundice was apparent . D1agnosts :
Hon-A, Non-8 hepatitis.
80J 1925 C- K444 10 IIC9 (b) (6) 5/29/84 Thh 26-year old r-1e beca• aware that she Poss1bly*'"
was pregnant after receiv ing one lnject1on of
vaccine . The vaccine was adalntstered approxl -
aatelv l ac,nth after conception . She experienced
a spor,taneous abortton at 18 weeks after feta 1
death In utero . No atcroscop1c exa111inatton was
COIIIIJletidl>Othe fetus. The subject prev1ous1y
delivered two healthy infants without coaplt - 0
cation of pregnancy . She had no •nown allergies. 0
0
• Cltnlca l investigator ' s IIHess111ent

••c Jlnlcal monitor ' s assess111ent . · -
vi
30181/ I
f iblt 8 (Cont.)
Adven;e Cxptrle•ces to Yeast Rt<ollbtrwnt Hepatitis 8 Yacc1ne
lot o(
~ mu §8-INO Yocclftt
Clates
Malnl\tertd
Datt of Oate Vaccine•
..1n!!L leporttd S•-,ry of [vent ., Rtl1trd
801 (b)(6) 192s C- IC444 10 . , (b) (6)
(b) (6) (b) (6) 11as A JS-year old f••l• subject coac,1 ■ tned of head- Probably
Not
ache one day afttr "celvtn, t~ third Injection
{b) (6) of vacctn,. The headache persisted for three days
and "u 1ccOt11>1nled by a sore throat and swollen
eyn . She wu adllltte-d to hosptte I on (b)(6)
with a dta9nosls of cllntcal viral 11enlngltl~ .
She recovered without sequelae .
803 1925 C- ICCU IO IICg (b) (6) ln/84 A 43-year old •1• p&tt,nt ■ rp,rtenctd sucl~en No
onset of blp1rtet1l headache, upset stoaec~.
confusion 1Dd er~resslve aphasia l days after
recetvtn9 t•e 1st Injection of vaccln,e . His
neurol09lc era• and vttal st1ns 111ere within
nor111l ll■ tts. A CAT scan of the head was also
nornil . His WBC ws slt,titly elevated with•
shift to the left . By (6)(6) syac,tom rnolYtd
spot1t1neously. TIie pttl•nt has I history of
■ult1plt cht ldhood 111 er91ts .
811 1925 C-«446 20 . , (b) (6) This 28-ytar old •le w1th underlying reM l \
( l tnJtct !Olis) dlse1se and rec,ntly Initiated htaOdlalysls.
die-cl 1pproxl•tely one ■onth after 1dlllnls-
tr1tlon of vaccine. The Investigator reported \
816
dNt.11 WIS due b vucullt Is . --1
192S C- K4U, 40 IIC9 (b) (6) 5/11/85 This 57-ye,r old f-le hta>dlalysls pat ien t No
(bl (6)
with sev•r• diabetes -lllt•s, hypertrf9ly
(b) (6) cerld•l1, hypert,1 . .11, atheroscltrottc
cardlovascul1r dtseast and 1ne■ le, exptrNI
1pproxlNtely 6 aonths after adlllnlstr1tlon
of the 3rd Injection of vaccine . ~•th was
due to ~ocardlel l11fer-ctlon .
lllf, 192S C- K446 (b)(6)
(b) (6)
4/15/85 This S7-yur old Mlt subject hid a history
of coron1ry utery disease with angina 1nd end-
(b)(6) stage renal disease (Jx/week ht90dle1ysts) .
Death was due to "VOCln:I la 1 tnf,rc t ton.
116 l92S C- K446 40 ac9 (b) (6) 2/5/85 This Ct-year old •1• P1t \ ,nt hid end -stage "nal llo
(b) (6) dlse1st (J•twe• •--,cft1lysts). Death was due to
respiratory arrest, aspiration asphyxia, end- stage
r-eaal and coronary artery disease.
•c11nlcat lnvestlgnor ' s nsessnent , 0
0
l018f · l
1111186 ,.,.
0
N
Table a (Cont.)
Ad11erse [aperlences to reut RecOllt> lnant Hepltltls 8 Vacc Int
Lot of Oates Date or Ode Vacc Int•

~ lli!...l 88-lN0 !.lUJM Dosi Ada1 n Is tered _illfil.... Re(!orttd s-~ or [vent !!.!ll!!
8Hi (b)(6) 1925 C-U46 40 .:9 (b)(6) (b) (6) l/5/85 The patient, a 79-yHr old Nlt, had end- stage Ho
(b)(6) ren.1 dhuse (3ic/-elc. heaodla\ysh). Death -s
caused by cardiac arrest, atherosclerosis, end-
stage renal dheue, and -.,lt1ple ayel«-.
8H, 1925 C-l4U 20 .:9 (b) (6) 1/22/85 Thh 11-yur old re-1• patient had I history of No
chrDftlc reruil f11lure, Parkinson's Disease,
d-ntl&, and abdoalnal an,urysa. TIit pat1ent
rectlYH b1wekly fletlod1alysls . Her death WU
d~ to urdlopulaonary 1rrut, ure11l1, chronic
renal failure, and abdc:wlnal aortic 1neurys■
without rupture.
116 )925 C- 11;44(> 40 a;g (b) (6) 1/22/85 This 49- year old•1• 1>1tlent had a lllstory of
cardiac ayopathy and chronic renal failure
(b)(6)
(3J/wet ~t90dlalysts). Hts death 11111s due to
cardlu arrnt, 111.11.onary tdt■a, and end- stage
kidney disease.
(b)(6) US/85 ~ SJ-year old fta1lt subject ~d I history or No
816 1925 c-«446 20 •v hyperttM1on, diabetes ■e111tus. cirrhosis,
(b) (6)
seven renal osteodystrophy and tnd-stage renal
disease (lx/week h~l1lysls) . Death was caused'
by congesthe h11rt fatlu~. renal fallur., and
severe arteriosclerosis.
Rlf> 1925 C-HU, 20 • i t (b)(6) J/22/85 This i3-~•r old •le h~11lysls patient wi th No
(b)(6) (SRO ind severt peripheral vascular disease, ws
(b)(6) ~ospltellztd for I left f1911n1l-popllte1l bypass
and lll■tl■ r s~Oecte19V 1ppro1l•tely 2 -ths
after adlllnlstratlon of his 3rd Injection of
vaccine. His hosptt11 course was COIIP11cated by
posto~r1tlve blood loss, hypotenston and hyper-
kll-la. Ht sullnquently uperlenced a nspl ratory
arrest requiring resuscitative •asures . Post
rnuscttatlon, the patient ws c«.atose and
decerebnte. His condition further deteriorated
and he died 4 days after 1dlllsslon to the hosp1tal.
•CJ\nlcal Investigator's assessaent.

0
)0181 - 3 0
1/19/8& 0
1.,-4
'-"'
Tab le 8 (Cont.)
Adverse £xpfrlences to Yeast RecOllblnant Hep1tttls 8 Vuclne
Lot of Date\ Oatt of Datt nee lne•

~ w.u H=.rn !lli1D! goie Adlllnt1tered .!nnL Ae~rted ~-a of (yent Re lated
816 (b) (6) 192S C-l44' 40 acg {b) (6) (b){6) 2/5/85 rhts 37- year old feaale subject bad I history of
diabetes •llltus ind tnd-stagt rtl\lll disease
Ito
(b)(6) Her dtath WIS c1used by
(2x✓-ek hea>d1alysls) .
sepsis. tnd- st.ge renal dlst1st. acute respiratory
distress syndroat, Infected dl11ys1s 9r1ft. and
dtabetes •llltus.
825 1925 C- l91S 100 •g (b)(6) S/14/85 fhls 31- year old •1• heaodta1ys ls patient with
[SRO, d iabetes •111t.us and hyperttmlon , dltd lB
No
days after •da:tnhtrat\on of his flnt lajectfon of

vacc Int . Ole CIUS ■ of death WIS reportN u
card lee arrllythala secondary to tnd- sbge rena 1
disuse .
625 1925 C-l'JI 5 l00 •9 (b)(6) 9/11/85 fhls 73-yur old ,,_1e hetlodlalysts p1tlent with No
ESRD. diabetes •llltus, hypertension, and hypo-
(b)(6) parathyroldls•. was hospttaltztd 5 days after
1dlllnlstratl011 of her 2nd Injection of vaccine
for a possible CVA. On tM day of adtlhslon.
the patient tlld been rtteh-11111 her schedule dialysis
treat:.ent during which she COlll)lalned of left- sided
..,.atness. £19ht ••ys 1fter hosplt1llz1tlon, the
patient uplred. Death - s nportd to be due to
■ CVA secondary to diabetes 1ssoclat~ vascular
dhease .
C~ll13] 40 1Kg (6) (6) 4/8/85 This lO-year old aale swbject hid a history of Ito
838 1925
{b){6) coro111ry artery ctlsuse and end-stage ~nal
(b)(6) clhuse. K1s death was due to acute ayocard la l
Cbl (61 tnrarctlon.
I 838 1925 C- ll13] 40 •g

(b)(6)
(b)(6)
(b)(6)
10/11/85 fhls 46-year old aale •talys1s patient vlth a
history of diabetes •llltus end dtabttlc
nephrOjMlthy, di.ct 2 110nths after 1dlllntstr1tlon
No
(b) (6)
ef his 3rd Injection of vaccine . 0Hth WIS due
\ to cardiac arrest secoftd1ry to llyperhle■ita .
I •clln lea 1 lnwestlg■tor's assess•nt .

3018 [ - 4
1/1'18• 0
0
0
~
~
Tilblt e (Cont.)
Adwtrst Eaptrltncts to Ye•st Rtcoab1nant Kt~tltl\ 8 Yuclne
Lot of Oates O.tt of O.le VilCC lne•

~ Cilse I Ba-JND Yilttlne fose M!lnlstere-d [vent R12orted ~-a of Event Reltted
661 (b) (6) 192S C-«5'4 10 •9 (b) (6)

(b) (6)
(b)(6) 10/28/85 This •Z-1/'tilr old •lt ~Ith heaopblll• type A loHIS
hospltallled on, day post his 3r~ Injection of
No
(b)(6) wecclne for •ltM and ll9hlht1dtdntss . His past

aedtc ■ l history ws s111ntf1cant for recurrent GI
bleeding, duodenal and 1ntr1l ,astrlc ulcers, ind
aulttplt lleaerthrous. On adatss Ion to th,
hospital m 1ndosco,II' 1111s perfor.d \lllch showed
a ht90r~l"1 telan11lectaslc site In th• dl1tal
1tna of the st-ch. Th• pat lent r·K thed 4
units of wttole blood and dallr u-yopredp1tlte
Inf us Ions. He ..-s dhclllrged after 5 days when
there wu no further cllnlul or laboratory
evidence of 61 bl1tdln9 .
a•• 1925 c-a:nz 5 •9 (b) (6)

(b) (6)
6/,'4/85 Tht neonatal •It rtc•tved ~BIG 1M his first
lnjec t Ion of vacc Ina at b I rth (b) (6) On
Un\\hly
(b) (6) the fifth and sixth days post-vaccination, ht

had a lftlPtraturt of 39•c. The Infant received
ti,leaol and hh teap9retvr-. ntur•tf to nol"lllll.
fie rKtlYN hi, se,ond 11kt third Injections of
vacclnt wHho11t te-.,arat"re elevat1on .
1!64 1925 C-k/lZ 5 •9 (b) (6) 6/24185 nth •1• a.on,te r.cthe4 ont dose of Kl.16 at UnHhly
(b)(6) birth (b} (6) . 1M dtveloped ptlyslolog1c
(b) (6) jaundice Ofl dtY 4 (b) (6) lfttr bl rth. The
jaundice resolved by day 7. Tll• first lnJec-
tton or vacclnt ws 1da1nlstered on (b) (6) The
tnf111t reuhed tM second 1nd third Injections
of vice IM wtOout loci 1 or sysu.lc <011111• lnts.
864 1925 C-k1l2 S IIC9 (blt6) li/24/85 On tbe first day of lift, th1s , ... 1, neonate Unlikely
(b) (6) had a fever of 101 . 1"F . The chi ld rec:elv~ one
(b)(6) dose of tel6 1t birth. The foll-109 day her
t~•rttur• was rior.1 1nd she received ti.r first
Injection of vaccine. n,en were no local or
systealc cOllll)la\nts after the first, second or
third tnJectlOfls of v1cclne .
81,4 1925 C-J:;132 5 ac:9 {b) {6l li/24/65 'fhh ult neonau was reporte4 to hl'tt develope-d Unlllt ly
(b)(6) J1undlc1 durlnt the post-n.t1l period . !ta had
recetvt4 OM dos• of HSIG at ~lrth (b)(6) and
his first \njectlon of v1ccln. Uine days liter.
Nh secon4 Inject Ion of vacc111e win adlllnhtered 0
on (b) (6) 0
.,,.
0
•cltn lul lnvestl91tor•s assessaent. VI
30181 - S
1/li/86
lablt 8 (Cont. I
Adwerie hptr l encn to Yeast RecOllbl111nt Kepet\th 8 Vacdne
lot of Date~ Oatt of Datt Vue Int•

~ illLl U:.Ill rudM M•lnlJterfd -1!.l!!L Reported Re latfd
(b) (6) l'J2S C-U32 5 IIC9 {b) (6) (b)(6) 9/19185 This one day old full - t,,.. Mlt Infant with 1p9ar No
scores of 9 at both 1 a11d 5 ■ lnutes vu , nterN
Into UU4y 864. ltt Nctl¥ed one 1nJ,ctlon of ttep-
8-6-tJH on Ue clay or birth and hh ht 1njtctlon
of vacclnt the rollowln~ day . Thf infant did veil
until tw days post-dtlhery wlltn poor fteillng VIS
noted . A canl\1c evaluation rtwe1led 1 .,,..,r alMI
possl•le 1trl1I ieptal dtftct. Nts cllnlc1I condi-
tion deterlor1ttd requiring lntllbltlon and tht
1d•lnlstr1tlon of pr.ssor 111d diuretic 19ents .
The lnhnt died 011 (b) (6) after ckculatory
collapse tnd Ult onset of 1rrhythlll1s . An
1uto11sy reve1led lntr1cranl1l, renal uld hep.at le
bt.arrh19,. hllPOPllSII of the left 1urlclt IAd
ventricle. a patent fortaen ovale, •n atrl1l
sept1I dtftct, and aspiration pHi...nla.
86' 1925 C- l217 10 . , (b) (6) 9/24/85 11111• hours arttr ad•lnhtrat1on of Yatcfne, No
this 46-yeir old ,_1, health cart worker
nperltnced 91ner1ltud prurlt Is (vl thout rash )
wfllch 1ncr•ued In Intensity ovtr th sllbsequtnt
6 hours . ,rur\tls continued during the next 24
hours 1cc011panttd by trrtt1btllty, ••usea, •n4
1M1rat11es I• ta the aru b1nuth th• l ert breast.
Th1se s ~ t - NSOIYed on th• 2n4 •nd 3rd days
post- Yacdnattot1. ltollfenr, thl part lclpant
nporttd that her utreelt1es relt stiff Ind
IIHYy. Her ,ast Mdlcal history 1s st9ntflt1nt
for par1thesl1s vlllch occurr~ one year prior
to vec:cln.tlon 1ft1r • • u ws sw,-,\c1Hy
rl90wed ,,_ her breast . The lnvestl91t0r
felt tti.t the subject's re1ctlon had 1n
-tlonal COllpOnent 1nd wes not r1l1ttd to
v1cclrle .
30181 -6
1 /19/86
Tal>le II (Cont.)
Adverse Experlences to Yeast RecOllblnant Hepatitis 8 Yaccln,
lot of Oates O.te of Datt vaccine•

~ cu,' 88-lND vacctne l!ou Adalnlstem Cnnt Re2ortect ~-a 2r [vent Rt lated
87S (b)(6) 1925 227'J: •O IICCJ (b) (6) (b) (6) CJ/24/l!IS Jh1s 53- year old ,_le hetlOdlllysls patient vllh No
Heptnu: (b)(6) an 18 mnth history of widely •t1staslzed 1deno-
cartlnoaa of the bA1St In addition to COPO, ffTN,
ur-tc perlunllth and renal failure, wu entered
Into st•dy 1115 and randoelzed to recelYt pl1saa
derlYed heJ)ltltls I ,1cclnt . Tt1 lrty-ntne days
after 1daln\str1t1on of the 2nd Injection of
Ylcclne the patle11t died of resplr1tory arrest.
8JS 1925 C-K931 40 IICCJ (b)(6) CJ/13/85 Forty- snen, da~ after 1delnlstratlon of th• 2nd No
(b)(6) tnjtctlon or ~•cctne, this U-ytar old f-1•
patient was hosp1taltzed for 111 lnfarcted bowl.
[,rploratory sur,iery wn perfoT'Md end the
fol1owtn9 day the patient uptrtil.
1175 1925 C-l13J 40 acg {b) (6) 914/85 A 32-yur old •lt h.-cfl1lysh pathnt r.cthed Poulbh'"'
• 20 •t lntr..,scular Injection of ,,cclnt Into
Hell deltoid (total dou 40 11C9). The pet lent• s
left ,,. suhequently btca• swol!en, stiff and
sore. Theit sw-.,tcas persisted for ont week ind
then subsldtd. The pat1fllt did nol receive any
further lnJecttons.
815 1925 C-l931 •o acg {b) (6) "4/85 Three days 1fter 1dlltnlstr1tlon of the first Possible*"
Injection of ,acc1ne, this 11-tHr old •I• heao-
d11tysts pet1tnt developed g-r•llled ■chlMSS
1nd a hHdlCllt . forty- eight hours after onset of
these SYIIPlOIIS, ht developed• flu- 11ke syndroae
~Ith• tft!Ptraturt of 1oo•F. The pltlenl did
ftot receive any f,rther vaccine 1ftjectlons .
BIS 1915 2271'. 40 acg {b) (6) unt 914/85 A. JO-y~u old • l t dialysis pat1eftt doelOl)NI 1n No
Heptavu ■nspectfle-d Illness. r~u\rln9 hospttallzatlon,
followtnt adllln1strat toft of th• ffrst Injection of
Yacc1ne. The lnyestlgator stated the •ttlness•
was not rel1ted to Y1cclne . The p1tt111t did
11ot rtetlvt Mld1tlON I nccfne Injections.
"C llnlc1l lnvestlga,t or' s aness•11t.

*"Clinical mnltor's 1ssess•nt.
l018(-J 0
1 /19/8f> 0
..,.
0
-.j
hble 8 (Cont . )
Advnst (xperlrncu to Yust RecOClb ln•nt tlrpatlth B Vutlnt
Lot of O.Us 01te of Date Vacclnr*

~ Cue I 88- INO ~ Oose r.dtll nh tered £vent le!i!!rl~ ~--r:w: of tvi•t lle l ated
890 (b) (6) 112S C-l2l 5 lO IIICCJ (b) (6) (b) (6) S/6/U Ttl\s 25- ynr old feM le n1bject ncorded a te~- Unlikely
(b) (6) erature of 100. i-r sneral days after adlllnhtra-
t Ion of a ,,cond ln}ectton of vaccine . t. CBC
coaplettd at th1t tt• revtaltd I no.--1 WBC with
& no.--1 dlff~ntl1l but I plateltt count ',treater
thin Ix 1061 was noted . Bone •rrow
uaal Mt ton revea'ltd n-rous 1N91taryocytes . A
pre- ulstlng ayeloprolHeratlve disorder h
considered the ll()St likely dt1gnos ls
B83 1925 C- l220 10 •9 Cb) (6) 4/l0/95 fht subject Is • dental studtnt who doeloptd per-
(b) (6) slstent cough and tiredness . Hews seen by•
physician approxlNttly 139 deys after his
second Injection of vaccine and,..., tentatlfel y
diagnosed as having chr0t1lc l~hlllc leut-11 .
889 1925 C- IC937 to •9 (b) (6) 9/24/95 Fourte-en hours after adalnlstntlOfl of ttt. 1st Probably""
Injection of v•cclne, this 37 - year old f _ l ,
noted hcla I warwth Ind f 1 LISII ln9 lnt Ing 45
alnutu . She s11bsequently dotloptd facial
urtturl~ . TM 11rttc1rh Wrt tretted w1th
cold packs . All SY!IPtGaS subsided wtth1n 12
hours . nie subj.ct recehtd llenedryl prior to
the second and third tnJttt!Ofls 1114 !tad no
poit-w■cclnatlon reactions . Sht has no known
known history of 1lltr9les.
*Cl ln lul lnvut l91tor' s asseu•nt .

""Cl\n lc,l 190nltor' s 1uusarnt.
30181- 8
1/1 9/96
Tab le 9
Host Frequent Complaints (~l.0%) Reported by

1252 Health Care Personnel and Other Healthy Adults
During a Five-Day Period Following 3255 Injection of
Yeast Recombinant Hepatitis 8 Vaccine
Type of Complaint Frequency as%

Local (Injection Site)
Soreness 8
Pain 5
Tenderness 3
Prur1tis l
Systemic
Fatigue/Weakness 4
Headache 4
Nausea 2
Diarrhea l
Malaise l
Pharyngitis 1
Upper Respiratory l
Infection (Nos} l
31091/3
1/8/86
00040
Table 10
Statistical Tests Regarding Anti - Yeast Antibody
l. Test for Trend in Antibody Titer (Log Titer)

Time
Post Post Post
First Second Thi rd
Prevaccination Injection Injection Injection
Mean log Titer 10.6 10.6 10.8 11.0
Std. Error 0.05 0.07 0.06 0. 19
Number Tested 131 70 90 12
Conclusion: No significant trend in Log Titer (p = 0.70)
2. Test of Association between Change in Anti-Yeast Antibody (Pre vs.

Postvaccination Titers) and Incidence of Clinical Complaints (Logistic
Regression Hodel Controlled for Age and Sex)
Test x_2 ( 1 d. f.)
Post
First Inject ion 0. 14 0. 71
Post
Second Injection 0.04 0.84
Conclusion: No association between change in anti-yeast antibody and

incidence of clinical complaints
32451/1
1/23/86
00041
Table 11
Statistical Test of Association between Antibody to a Specific
Yeast Antigen (P60) and Incidence of Clinical Complaints*
Table of p Values
Clinical Com12laints
Level of Post Post Post
Antibody to First Second Third
P60 Injection Injection Injection Anytime
3 Months 0.4!9 0.60 0.95 0.76
(2 Month s Post
First Injection)
Change in Antibody 0.4:2 0.49 0.97 0.82
to P60 from
Prevacc i nation to
3 Months
* Mantel Haenzel Test with Responses Corrected for Study and Prevaccination
Level of Antibody to Pf>O. Test significant for p <0.05.
32451/2
1/23/86
00042
Table 12
Percentage (Propor1tion) of Healthy Adult Male Homosexuals with

Clinical Complaints Following Injections of Yeast Recombinant (10 mcg Dose)
or Plasma-Derived H~~patitis 6 Vaccine (20 mcg Dose) in Study 894
Type of First Second Both

Complaint Vacciine Injection Injection Injections
Local Plasma-Derived 42 (37/88) 35 (24/67) 39 (61/155)

( Injection Site)
Recombinant 30 (25/83) 35 (21/60) 32 (46/143)
Systemic Plasma-Derived 35 (31/88) 25 ( 17/6 7) 31 (48/155)

Recombinant 29 (24/83) 18 ( 11 /60) 24 (35/143)
Any Pl a srn.1-Der1ved 61 (54/88) 51 (34/67) 57 (88/155)

Recombi r1ant 51 (42/83} 47 (28/60) 49 ( 70/143)
Temperature Plasma-rnerived 2 ( 2/84) 0 (0/67) 2 ( 2/151)

~ 100°F (oral)
Recombi n1ant 5 (4/83} 7 (4/57) 6 (8/140)
31761/1
l /11 /86
OOOLJ3
Table 13
Anti-HBs Responses a1t 3 Months Among Health Care Personnel and

Other Healthy Adults Receiving Yeast Recombinant or
Plasma-Derived Hepatitis B Vaccine at 0, 1 and 6 Months
Recombinant Vaccine - 10 mcg Plasma-0eri ved Vaccine - 20 mcg

Age % with GMT S with GMT
{Years} Anti-HBs* (mIU/ml}~ Anti-H8s* (mlU/ml)**
20 - 29 92 (359/388) 68 91 ( 436/477) 107
30 - 39 78 { 87/112) 39 88 {277/315) 46
40 - 49 75 (21/28) 48 80 (124/156) 28
50 - 59 82 (14/17) 22 61 (66/108) 27
"' SIN ~2. l
** Responders on1y; titer in mIU/ml for recipients of plasma-derived

vaccine approximated as (b) (4) titer + 4.
30861/1
l /11 /86
00044
Table 14
Antl-HBs Responses cit 6 Months Among Health Care Personnel and

Plasma-Derived Hepatitis B Vaccine at 0, 1 and 6 Months
Recombtnant \faccine - 10 rncg Pl asma - Oeri ved Vaccine - 20 mcg

Age % with GMT % with GMT
(Years) Anti-HBs* (mIU/ml )'l\"A' Anti-H8s* (mIU/ml>-
20 - 29 96 (403/419) 96 95 (434/459) 148
30 - 39 89 ( 110/124) 53 93 (273/293) 56
40 - 49 88 (30/34) 45 88 (128/146) 40
50 - 59 81 ( 13/1 r,) 42 76 (81 /107) 39
* S/N ~2.1
** Responders only; titer in mIU/ml for recipients of plasma-derived
vaccine approximated as (b) (4) titer + 4.
30861/2
l /11 /86
Table 15
Anti-HBs Responses at 7/8 Months Among Health Care Personnel and

Plasma- Derived H1epatitis 8 Vaccine at 0, 1 and 6 Months+
Recombinant 'Vaccine - 10 mcg P1asma-Deri ved Vaccine - 20 mcg

Age % w1 th GHT % with GMT
(Years} Ant1-H8s• (mIU/ml }** Anti-HBs* (mIU/ml}**
20 - 29 99 (341/344) 1707 98 ( 412/421) 2830

30 - 39 96 ( 106/111 ) 694 95 ( 261 /274) 1050
40 - 49 97 (33/34) 484 94 ( 134/142) S28
50 - 59 90 (17/19) 442 85 (81 /102) 360
+ Includes some responsi~s measured at 9 months when that was the first
blood sample obta i ned following the third injection of vacc i ne
* S/N ~2.1
** Responders only; tite1r in mIU/ml for recipients of plasma- derived

vaccine rec1p1ents approximated as (b) (4hiter + 4 .
30861/3
1/11 /86
000£1&
TABLE 16
Distribution of Ant1-H8s Titers at 7/8 Months

Among Health Care Personnel and Other Healthy Adults
Receiving Yeast Recombinant or Plasma-Derived
Hepatitis 8 Vaccine at 0, l, and 6 Months
S (Proportion) with Titer

Recombinant Vaccine Plasma-Derived Vaccine
Ant f -HBs T1 ter 10 rncg 20 mcg
S/N ~2.1 98 (498/509) 95 (930/983)
mru/ml ~10 97 (494/509) 92 (900/983)
mIU/ml ~100 89 (451/509) 78 ( 772/983)
mIUlm' ~1000 ~8 (2<l4/509) 53 (519/983)
* Titer in mIU/ml for recipients of plasma-derived vaccine

approximated as (b) (4)titer + 4.
wva/31221
l /11 /86
000117
Table 17
Anti-H8s Responses at 12 Months Among Health Care Personnel and

Plasma-Derived Hepatitis 8 Vaccine at O. 1 and 6 Months
Recombinant Vaccine - 10 mcg Plasma-Derived Vaccine - 20 mcg

Age % with GHT % with GHT
(Years} Anti-HBs* (mIU/ml)** Anti-HBs* (mlU/ml)**
20 - 29 98 (115/118) 343 99 (233/236) 954
30 - 39 94 (74/79) 235 97 ( 67 /69) 441
40 - 49 91 (21/23) 238 87 ( 33/38) 117
50 - 59 88 ( l S/1 7} 151 87 (46/53} 1 H,
* SIH ~2. 1
** Responders only; titer in mIU/ml for recip ients of plasma-derived

vaccine approx1mated as (b) (4)titer + 4.
\
30861/4
1 /11 /86
00048
TABLE 18
Distribution of Anti-HBs Titers at 12 Months
Among Health Care Personnel and Other Healthy
Adults Receiving Yeast Recombinant or Plasma-Derived
Hepatitis B Vaccine at 0, 1, and 6 Months
% (Proportion} with Titer

Recombinant Vaccine Plasma-Derived Vaccine
Anti-HBs Titer 10 mcg 20 mcg
S/N ~2. 1 95 (225/237) 95 ( 400/422)
mlU/ml ~10 90 (213/237) 92 (387/422)

mIU/ml ~100 65 ( 155/237) 70 (294/422)
mIU/ml ~1000 25 ( 60/237) 37 (157/422)
writer in mIU/ml for recipients of plasma-derived vaccine approximated as

(b)(4)titer + 4.
31741/1
l /11 /86
Table 19
Percentage (Proportion) of Health Care Personnel and Other Healthy Adults

With Clinical Complaints During a 5 Day Period Following
Injections of Yeast Recombinant or Plasma-Derived Hepatitis B Vaccine
Type of First Second Third All

Come la int Vaccine Injection Injection Injection Injections
Local Plasma-Derived 13 ( 92/687 ) 10 ( 67 /650.) 11 ( 55/480) 12 (214/1817)
(Injection
Site) Recombinant 20 ( 248/1252} 14 (157/1162) 17 (139/841) 17 (544/3255)
Any Plasma-Derived 24 (164/687 ) 18 (119/650} 18 ( 87/480) 20 (370/1817)

Complaint
Recombinant 34 {426/1252) 23 {263/1162) 23 (196/841) 27 (885/3255)
Temperature Plasma-Derived 3 18/681 ) 3 ( 20/640 ) 2 ( 10/467) 3 ( 48/1788)

>100°F
Tora!) Recombinant 4 45/1217) 3 ( 28/1111) 4 ( 27/769) 3 (100/3097)
00050
APPENDIX I
Lot Numbers of Vaccine Used in Clinical Trials

0005 1
Lots of the yeast recornbtinant hepatitis B vaccine used in the clinical

trials s ummarized in this report are identified by an alpha -numeric code
consisting of two or three segments. In the Interim Submission (Report 112)
issued in August 1985, m,rny lots of vaccine were identified in text and
tables using either the prefix or internal segments. In the present report,
al 1 lots are identified by the 5 digit suffix segment. To facilitate cross
reference between the Interim Submission and the present report, the
complete lot number for each lot of vaccine in use is listed below:
934/C-J625
972/C-K444
974/C-K446
978/C- K563
979/C-K564
985/C- K732
986/C-K733
987/C-K734
993/C-K937
819900/18066/C-L215
81766B/18067/C- L216
819910/18068/C- L217
81992A/18070/C-L219
81954I/18071/C-L220
89303/1005/C- L915
89426/22930/C-M718
85860/22123/C-M125
85861/22124/C-Ml26
mtruNE AFFI NITV
VACCHIE
00052
SUMMARY - IM~UNE AFFINITY VACCINE
Recombinant hepatitis B vaccine from one lot (934/C-J625) produced by an

immune affinity purification procedure has been adm1n\stered to 75 initially
seronegat1ve health care personnel and other healthy adults in 3 studies
(Table l). with 72 of these completing a 3 injection regimen of vaccination.
The serologic and clinical data relating to this lot are sunmarized separately
because this procedure will not be used for the commercial product.
Table 2 shows the anti-HBs responses in persons i111111unized at 0, 1, and 6
months with 10 mcg doses of vaccine produced by the immune affinity
procedure. Al l vaccinees developed protective levels of anti-HBs (mIU/ml ~10)
7-8 1110nths post the first injection of vaccine. The 9e0111etric mean titer was
1607.0 •IU/ml. Twelve months after the first injection of vaccine , 96% of the
vaccinees sti 11 had titers ~10 111IU/ml. However, the geometric mean titer
declined to 422 mIU/ml.
There have been no serious or alarming reactions attributable to the inmune
affinity purified vaccine. While one adverse experience report has been filed
with the OoBRR (Table 3), the reaction noted did not appear to be related to
the vaccine. There was also one subject whose 2, 3, and 4 month
post-vaccination sera were pos i tive for ant1-HBc. His pre-vaccination blood
sample and his 1, 5, 6, and 7 month blood samples tested negative for
anti-HBc. The subject has been positive for anti-HBs since one month
following the first injection of vaccine. None of his blood samples have been
positive for HBsAg. All samples had nonnal levels of AST and ALT.
Table 4 shows the frequencies of clinical complaints reported following 206
injections of the vaccine. Reports of injection site discomfort and systemic
complaints were made with frequencies of 50% and 15%, respectively. The
frequencies of specific injection site complaints are shown in Table 5. The
most frequent co~laints were soreness (34%), pain (7%), and tenderness (5%).
The frequencies of specific systemic complaints by body system are shown 1n
Table 6. Complaints occurring at frequencies of ~1% were fatigue/weakness
(4%), headache (2%) , pharyngitis (2%), malaise (1 %), rhinitis (l S). upper
respiratory infection (not otherwise specified) (1 %), nausea (1 %), and
diarrhea (1 %).
l:lva/3131 I-1
1/6/86
Table 1
Clinical Studies of Health Care Personnel and other Healthy Adults Receiving
Ye.st Rec:Ollbinant H!!petHis B vaccine Procllced by An InalaJne Affinity F'ethod
'& Slbjects
Da!te Vaccine Planned !. l!ll!h ~ti..f-!Bs 1111111!
Popu1Ation Study fJ lmte5tlgator l~tlon Initiated Status Lot Dose Regi- (Vaccinated) S/H ~2.1 111IU/•I ~10 (~ths)
----
HNlthy 119 Bishnp f!!rck & CO. • PA 1/13/83 In pl"OgN!SS C-.1525 10 IIIC9 0 1 6
0 0 IIIOS. IS ( IS) 100(14/14) 100(14/14) 12 111)$.
Its
., HNlth C.re 192 Diensug Boston 11/10/83 In progress C...J62S 10 mcg 0.1,6 IIIOS. 30 (30) 96(25/26) 96(25/26) 12 mos.
F\lrsonM I
D«Mlth care 195 O.inhardt Nest O.nany 11/21/83 In progress C...J625 10111!Cf 0,1,6 IIIOS. 30 (30) 96(26/27) 93(25/21) 12 !IDS.
Pi2rSonM1
0
0
0
Ill
wa/31311/4 ""
1/6/S!f)
00054
Table 2
Antibody Responses Among Health Care Personnel and Other Healthy Adults
Fo110ld1ng Vacc1natio at 0, l, and 6 Months with 10 mcg Doses of
Yeast Recombinant Hepatitis B Vaccine Lot #934/C-J625
~ ldith Ant1-HBs GIIIT (11JU/ml}

Time All ResQonders
('1onths) S/t:J ~2. l IU/1111 ~10 Vacc1nees S/N ~2.1 mJU/ml ~10
l 36 (15/10) 9 ( 6/70) 1.0 7 .0 26.5
2 79 (8/73) 63 (46/73) 16. l 38.4 64.5
3 96 (67/70) 76 (53/70) 30.8 37.4 62.7

6 97 (69/71) 89 (&3/71) 52.9 67.5 79.7
7/8 100 ( 70/70) 100 (70/70) 1607.0 1607 .o 1&07.0
9 100 (60/60) 97 (58/1>0) l 024. 5 1024.5 1228.4
12 97 (65/67) 96 (64/67) 317.9 393.8 422.0
Studies: 779, 792, 795
wva/31311-6
1 /6/81>
Table 3
Adverse Experiences to Yeast Recait>\nant Hepatitis 8 Vaccine
Study-Case Date(s) Date of Date Vaccine

li!O. eo. ~ Lot gf Y!ICC i ne Dose Mninisterecl Event ~rted Su11m1ar~f Event Relatf!d 1r
g ;.--.;: er,
! C-J625 n:g A 30 year-old male s__,ject ~s noted to have
---
10 1/15/85
§ .;
0"1
.-!
~
~ I a serun Al T of 170 on r ~(
three IIOl'lths
after receiving the third dose- of vaccine).
~
0) one~ later. the senn ALT was 139. The

...._,,,;
subject's pre-vaccination ALT ~s 47. All
sera reM&ined negative for anti-fflk: and Jes.Ag.
The subject had been taking t1:10 antimalarial
dn.igs, O.loroquine and Fansidar, for Z 1110nths
prior to the ~ ~bleeding. During that
tim, he had been v1<iting East Africa.
tr Clinical investigator's assesSMent.
0
0
0
I.II
VI
Wa/31311/5
1/Zl/l!S
00056
Table 4
Percentages of Health Care Personnel and other Healthy Adults With

Clinical Complaints During a 5-Day Period Following 206 Injections
of Yeast Recombinant Hepat1t1s B vacc1ne lot ,f934/C-J625
Studies: 779, 792, 795
Type of Complaint Dose 1 Dose 2 Dose 3 All

Local (Injection Site} 55 (39/11) 44 (31/70) 51 (33/65) 50 (103/206)
Systemic 22 (16/71) 13 (9/70) 9 (6/65) 15 (31/206)
Any Complaint 63 (45/71) 47 (33/70) 54 (35/65) 55 (113/206)
Studies: 779, 792, 795
wva/31311-7
1 /6/86
00057
Table 5
Frequency of Local (Injection Site) Complaints Occurring ithin 5 Days

Among Health Care Personnel and Other Healthy Adults Foll01::11ng
206 Injections of Yeast Recombinant Hepatitis B Vaccine
Lot 1934/C-J625
Number of V ccine Recipients: 71

Studies: 779, 792, 795
Co!,!!l!laint Number Freguencl£ as I

Soreness 71 34
Pain 15 7
Tenderness 11 5
Stiffness/Tightness 4 2
Swelling 4 2
Ecchymos1s 2 1
Erythema
Prur1t1s
2
2 ,
1
Numbness
Pigment Change
1
, 0.5
0.5
Skin Mottled/Peeling ,, 0. 5
Parasthes ia 0.5
Papule
wannth ,
1 0.5
o. 5
~a/31311-8
1/6/86
00058
Table 6
Frequency of Systemic Complaints by Body System Occurring Within 5 Days

Among Health Care Personnel and Other Healthy Adults Following
206 Inject1ons of Yeast Recombinant Hepatitis B Vaccine
Lot #934/C-J625
Mumber of Vaccine Recipients: 71
Studies: 779, 792, 795
Frequency as% Frequency as %

6od~ S~stemlComnlaint (Mumber} Bod~ S~stem£CO!!l!laint (Number}
Whole Body/General 8 ( 17} Infectious Syndromes 1 (2)
Fatigue/Weakness 4 (9) Herpes Labia11s. 0.5 ( 1)

Headache 2 (5) Recurrent
~la1se l (3) Viral Infection. Nos 0.5 (1)
Sensation of Warmth. 0.5 ( 1 )
General
Respiratory 5 (11) Hemic/Lymphat1c 0. 5 (l)
Pha ryng it 1s 2 (5) Lyrnphadenopathy, 0.5 ( 1)

Rhinitis 1 (3) Cervical
Upper Respiratory 1 (3)
Infection. Nos
Cough 0.5 (1) fllusculoskeletal 0.5 (ll
Sinusitis 0.5 (1)
Laryngitis 0.5 (1) Myalgia 0.5 (1)
Digestive 2 ( 5}
Nausea 1 ( 3) Organs of Special Sense 0.5 (1)

Diarrhea 1 ( 2)
Dyspepsia/Heartburn 0.5 (1) Conjunctivits 0.5 (1)
Abdominal Pain/Cramps 0.5 (1)
wva/31311-9
1/6/86
ooosq
Table 7
Percentages of Health care Personnel and Other Healthy Adults With

Elevated Temperatures Our1ng a 5-Day Period Following 190 Injections
of Yeast Recombinant Hepatitis 8 Vaccine Lot #934/C-J625
Studies: 779, 792, 7g5
Temperature Dose l Dose 2 Dose 3
4 (3/70) 2 (1/63) 4 (2/57) 3 (6/190)
1 (1/70) 2 ( 1/63) 4 (2/57) 2 (4/190)
wva/31311-10
1/6/86
00060
Immune Affinity Vaccine
Study 779 - ~est Point , PA - Dr. R. Bishop

Healthy adults receive 10 mcg injections of vaccine from one of two lots at 0,
1, and 6 months.
Fifteen adults have received 3 injections of vaccine from lot C-J625 produced
by the inunune affinity 111ethod. At 7/8 110nths, 100% (15/15) of the
participants seroconverted (S/N ~2.1) and developed protective levels of
anti-HBs (mIU/ml ~10). The 6~T for these responders was 1758.l mIU/ml. Among
the participants with serology data at 12 months, 100% (12/12) were positive
for ant1-HBs (mIU/ml ?,10). The 6'11T for all vaccinees at that tinie was 402.3
mIU/ml. No serious or a lann1ng reactions attributable to vaccine have been
reported. Subjects continue to be followed for persistence of antibody.
Refer to the sunmary in health care personnel and other healthy adults for
P.or;nnnse.s of subjects vaccinated in this study \:11th vaccine produced using the
(6) (4) method . ·
Study 792 - Boston, MA - Dr. J. D1enstag

Initially seronegative health care personnel receive 10 mcg injections of
vaccine fr011 one of two lots at 0, l, and 6 months.
Thirty persons have received 2 injections of vaccine from lot C-J625 produced
by the immune affinity method, and 27 of these have received the third
injection. One hundred percent (26/26) of the participants seroconverted
{SIN !'.,2,1) and developed protective levels of ant1-H8s (mIU/ml ?,10) at nine
months. The ~T for these responders was 1400. l mIU/111. At 12 months, 961
(25/26) of the subjects were positive for anti-HBs (mIU/ml ~10) with a 6111T of
329 .8 for all vaccinees. There have been no reports of serious or alarming
reactions attributable to vaccine. Subjects continue to be followed for
persistence of antibody.
Refer to the summary on health care personnel and other healthy adults for
responses of subjects vaccinated in this study with vaccine produced using the
(b) (4) method.
Study 795 - west Gen1any - Dr. F. Deinhardt

The study population consists of health care personnel and other healthy
adults who are initially negative for hepatitis B serologic markers.
Participants receive 10 mcg injections of vaccine at 0, l, and 6 months from
one of three vaccine lots .
ldVa/31311-2
l/6/86
00061
Immune Affinity Vaccine
Study 795 - West Genaany - Dr. F. Deinhardt (Contd)
- Thirty persons have received 3 injections of lot C-J625 vaccine produced by

the immune affinity method. At 7/8 months, 10~ {29/29) of the subjects
seroconverted (SIN ~2.1) and developed protective levels of ant1-HBs
(mIU/1111 ~10). The lil:1T for these responders was 1735. 7 mIU/ml. Ninety-three
percent (25/27} of the participants were positive for ant1-HBs (mIU/ml ~10) at
12 months. The Gf!lT for all vaccinees at that time was 271.5 mIU/ml.
Refer to the summary in health care personnel and other healthy adults for
resoonses of subjects vaccinated in this study with vaccine produced using the
(b) (4) method.
wva/31311-3
1 /6/86
00062
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepatitis 8 Vaccine,

Study 779
PURPOSE: To evaluate antibody and clinical responses to the

vaccine among healthy adults who are negative for
hepatitis B virus serologic markers .
VACCINE: Yeast Recombinant Hepatitis B Vaccine

Lot 934/C-J&25 (10 mcg HBsAg/ml)
Lot 972/C-K444 (10 mcg HBsAg/ml)
PRINCIPAL Robert P. Bishop, M.D.

HdVESTIGATOR: Health Services
~erck Sharp and Dohme
west Point, PA 1948&
SECONDARY E. P. Avancena, M.D.

INVESTIGATORS: Health Services
Merck Sharp and Dohme
West Point. PA 1948&
Joseph C. Rogers, M.D.
Health Services
~erck Sharp and Oohnie
West Point, PA 1948&
Joseph P. Romano, M.O.
Health Services
Rahway, NJ 07065
STUDY LOCATION: ~erck Sharp and Dohme

West Point, PA 19486
DATE INITIATED: July 13, 1983
DATE COMPLETED: In progress
251 ll/1
12/26/85
00063
Study 779
STUDY The study population consists of 41 healthy adults of

PROCEDURE: either sex (excluding pregnant women) employed at Merck
and Co . • Inc., who were initially negat1ve for HBsAg.
anti -H8c and ant i-HBs, had a normal ALT level and had
not previously received any hepatitis B vaccine.
Eligible participants receive a 1.0 ml (10 mcg HBsAg)

intramuscular injection of 1.1:,rdno n.-1\rlured by either
the immune affinity or the (b) (4) procedure at
0, 1 and 6 110nths . Study participants are asked to
take and record their temperatures for five days after
each injection of vaccine and to record any local or
systemic complaints that they may experience.
A blood specimen (10-15 ml) was obtained from each

participant approximately two weeks before
vacdnation. Post-vaccination blood samples (10-15 ml)
are obtained monthly for seven months and at 9, 12 and
24 months following the first injection of vaccine.
Samples are assayed for HBsAg, anti-HBc, anti-HBs and
ALT. and these may be assayed for antibody to antigens
in yeast extract. Samples with an anti-HBs titer ~
25 mIU/ml units are tested to determine the relative
proportions of anti-! and anti-g activity.
STUDY RESULTS: HEALTHY ADULTS (Immune Affinity Vaccine):
10 mcg Lot 934/C-J625 at 0, 1, and 6 months
1. Number Vaccinated:
Injection No.
_ l_ __2_ __3_
15 15 15
25111-2
12/26/85
0006'4
Study 779
RESULTS: (Cont.) 2. Serologic Results:

Serologic data are available for 15 participants
at 7/8 months. One hundred percent (15/15) of the
participants seroconverted (S/N ~2. l) and
developed protective levels of anti-HBs (mIU/ml
~10) at that time. The Gr:JT at 7/8 months was
1758. 1 mIU/ml (all vaccinees and responders by
either cutoff).
Among the participants who had serology data at 12
months, 100% (12/12) were positive for anti-HBs
(mIU/ml ?10). The G~T for these vacc1nees was
402. 3 mIU/ml.
Refer to Table 1 for ant1-HBs responses and GMTs

for other time intervals.
3. Clinical Complaints:
Clinical follow-up data are available for fifteen
participants after each injection. The overall
frequencies of complaints are presented below.
Type of Frequency in~ by Injection No.
Comolaint 1 2 3
Injection 80(12/15) 73(11/15) 73(11/15)

Site
Systemic 33(5/15) 20(3/15) 7(1/15)
Refer to Table 2 for listings of specific clinical

complaints by injection number. Maximum
temperature data are provided in Table 3.
There were no serious or alarming reactions
attributable to vaccine.
HBV ~arkers (Ant1-HBc)
One subject had serum samples that tested transiently
positive for anti-HBc. The 2, 3, and 4 month
post-vaccination sera were positive for anti-HBc. His
prevaccination blood sample and his l, 5, &, 7, 9 and
12 month blood samples were negative for anti-H8c.
None of his sera were positive for HBsAg. All samples
~ere nonnal with respect to AST &nd .ALT.
25111/3
12/26/85
00065
PUBLICATIONS: Scolnick EM, ~clean AA, West DJ, Dienstag Jl, Watkins
E, Deinhardt F. Antibody and clinical responses
among healthy adults to a hepatitis B vaccine made
by recombinant DNA. In: Vyas Gl\l, Dienstag JL,
Hoofnagle JH, eds. Viral Hepatitis and Liver
Disease. Orlando: Grune and Stratton, 1984:315-17.
Scolnick E~. McLean AA, West OJ, McAleer MJ, ~iller WJ,
Buynak EB. Clinical evaluation in healthy adults
of a hepatitis 8 vaccine made by recombinant DNA .
JA~ 1984; 251:2812-15.
25111.,..4
12/26/85
Table 1
ANTIBODY RESPONSES FOLLOWING VACCINATION WITH RECOl18INAHT HEPATITIS B VACCINE
STUDY 0779
POPULATIOU HEALTHY ADULTS
DOSE 10 MCG
LOT CJ625
REG U1EH 0, 1, AND 6 110HTHS
INITIAL SEROLOGY: NEGATIVE
I X WITH Atffl-HBS I GMT I MIU/Ml l I

l---------------------------------------1-----------------------------------------------------I
I I I RESPOIIDERS I
TIME
(MONTHS)
l---------------------------------------l-----------------1-----------------------------------
I S/N >= 2 . 1 I HIU/Hl >: 10 I All VACCINEES I SIN>= 2.1 I NIU/ML>= 10
······································································•·*••·······································
I I I
I l MONTH 45X (5/11) I 'I. lY. t 11111 I 1.7 6.1 55.5
I I
I 2 MOUTHS 93Y. 114/15) 7lY. ( 11/15) I 32.0 44.7 ee.o
I I
I 3 t10tlTHS 100?. 114/14) 867. (12/141 I 60.5 60.S 83.5
I I
I 6 MOtlTHS 100?. 115/1S1 100?. 115/15) I 68 . 0 66.0 68.0
I I
I -7/8 NotlTHS lOOY. 115/15) lOOY. I 15/15) I 17511.l 1756.l 1758.1
I I
I 9 MONTHS 100~ I 14/14 l 100% I 14/14 l I 1319.9 1319.9 1319.9
I I
I 12 l10tlTHS lOOY. I 14/141 lOOY. (14/14) I 402.3 402.3 402.3
I I
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
0
0
0
0-
0-
·=
Table 2
PATIENT COUNT CLitllCAL COMPLAINTS
RECOt181NANT HEPATITIS 8 VACCINE
STUDT 0779
TREAT11ENT
LOT t1Ut10ER CJ6Z5
DOSE 10 t1CG
PATIENT CLASS IIEAllKY AOULTS
--- -------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES f 15 PATIEHTSI - DOSE l I
1----------------------------------------------------------------------------•
I DAYS POST VACCINATION I NUl'1BER
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------1
I O I 1 I Z I l I 4 I S I
WITH
•cOMPLAIHfS
****••••••••••••••••••••••••••*"**l*•••••••••l••••••••••l••••••*•••l•••••••••••••••••••••l••••••••••I•••••••••••••••••••••
•
REACTION, LOCAL IIHJtCT. SITEI I 11 I• S
I
I 3
I
I 1
I
I 0
I
I l
I
I I
I 12
I I 73.3%1 • I 33.3%1 I c 20.0;:1 I I 6.77.I • t 0,0%1 I I 7.1%1 I I f so.ox,
-----------------------------------1----------
SORENESS I 10
----------
5
----------
l
----------•----------
l I 0
----------1----------1-----------
1 I I 11
I 66.T/.I t 33.3%1 I 20.0;0 f 6.77.1 I I 0.0%1 I 7.llO I 11 73.3%1
TEtlDEl!NESS I 1 0 0 0
II O o II II 1
6. 7%1 t 0.0%1 I 0.0%1 t 0.07.1 I I 0.0;1.1 I 0.0%1 I I I 6. 7%1
I I
ERYTH£t1A IREDNESSI I 1 O O O I O o I I 1
6.11.1 1 o.o;o 1 0.0;:1 1 0.0;:1 I I o.o;o I o.o;o I I , 6.7:t.>
I I I
STIF'fNESS/TIGHTNESS I 2 O O o I O o I I z
ll.3%1 ( 0.0%) f 0.07.1 f 0.07.1 I t 0.0%1 ( O.OiO I I I 13.3¼1
I I
ECCHYHOSIS I 1 O O O I O O I I 1
I f 6. 7¼1 I 0.0%1 1 0.0%1 I I o.o?.J I I 0.0;:1 I 0.0;:1 I I r 6. 7%1
-----------------------------------1----------l----------1----------I----------I----------•--------
SYSTEt1It I 4 I 1 I 1 I 1 I 1 I 1
· I----------I-----------
I I s
I I 26. 7% > I I 6. 7% > I f 6. 77. I I f 6. 77. l I ( 6. 7¼ I I I 7. uo I I f 33. JY. I
WHOLE BODY/GENERAL 3 l 1 1 1 l 4
•I t 20.0,0 I 6. 77.1 ( 6. 7% I ( 6. 77.1 ( 6. 7Y.I t 7. lY. I I 26. 7iO
I
FATIGUE/WEAKNESS I 1 1 l l l 1 2
6. 7%1 ( 6. 7%1 ( 6.7%1 ( 6. 77. I ( 6. 7Y.) ( 7.1%1 I ll.3¼1
I
HEADACHE I 2 0 0 0 0 0 2
• f 13.3%) 0.0,0 o.o:o
I
'
( 0.0lO ( I.OX) ( 0.0XI I 13.3iO
I
RESPIRATORY I 2 D 0 0 0 0 2
I I 13.3Y.l I D.0%1 ( 0.0%) 0.0Y.I
' 0.0Y.I 0.0iO
(
SINUSITIS
I
I l 0 0 0 0
' 0
I' 13.3%1
1 0
6. 7%1 I 0,07.) ( 0.07.1 ( 0.07.) ( 0.0%1 a.ex, 0
'
( 6. 7XI
0
C1'
.....
,.
Table 2 (Contd)
PATIENT COUNT CLINICAL Cot1PLAINTS
RECOHBINANT HEPATITIS B VACCINE
STUDY 0779
TREAT11ENT
LOT NUMBER CJ625
DOSE 10 t1CG
PATIENT ClASS HEALTHY ADULTS
----------------------------------------------------------------------------------------------------------------------------
I . TOTAL VACCltlEES I 15 PATIEHTSJ - DOSE 1 I
1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUMBER
CLINICAL 1----------------------------------------------------------------------------I WITH
COl1PLAUIT5 I O I 1 I 2 I 3 I lt I 5 I ICOMPLAINTS
................................... I,.......... ········••l••······••I••········
I I
.......... ········••I••········
I
..........
PlfARYHGITlS I SOPE THROATI I l 0 I O I 0 0 0 l
6.7)0 I o.o;n ( I O.0Y.J I I 0.0iO I o.o:o I 0.0Y.I I 6.7Y.)
I I
DIGESTIVE SYSTEM I 1 0 I l I l 0 0 2
6. T/. I I O. 0Y. J I I 6 • 7iO I I 6. 7iO C 0. 0Y. J C 0. 0% I I 13. 3% I
I I
DYSPEPSIA/HEARTBlmH I 1 0 I O I O O O 1
6.7?.I I o.o;o I ( o.o;o IC 0.0Y.I I 0.o:o I 0.0%1 I 6.7?.I
I I
DIARRHEA I O O I l I l O O 1
0. 0% I I O. 0% J I ( 6. 7Z J I I 6 • 7i0 I O. 0% I I O. 0% I I 6. 7% J
I I
NAUSEA I O O I O I l O O l
II O. o:o I I O. o;o I I O. 0% l I I 6, 7% I I O. 0% I I O. 0% I I 6. 7iO
-----------------------------------1----------l----------l----------l----------l----------l----------l----------1-----------
PERSOIIS WITH Ctlt1PLAINTS I 11 I 6 I ft I 2 I l I 2 I I 1Z
I I n.3%1 I I lto.o:o I , t6.7Y.> I 1 13.31.1 I c 6.7:o I , 1'1.3:1.1 I I , eo.oY.>
-----------------------------------1----------l----------1----------l----------1----------I----------I----------I-----------
PERSoHS MITH NO COHPUIHTS I lt I 9 I 11 I 13 I 14 I 12 I I 3
I I 26.T/.1 I I 60.0;0 I I 73.3?.I I I 86.71.l I I 93.3:o I I es.n:, I I 1 211.o;n
-----------------------------------1----------l----------l----------l----------l----------1----------I----------I-----------
PERSONS WITH HO DATA I O I II I o I o I II I o I I o
I I 0.0Y.I I I O.0Y.I I I 0.0%1 I I 0.01.1 I C 0.0%1 I I 0.0Y.l I I c D.0%1
0
0
,,..
0
0,
p
Table 2 (Contd)
PATIENT COUNT CLINIC AL CottPLl IHTS
AECOHBIHAHT HEPATITIS 8 VACCINE
STUDY 0779
TAE ATtfEHT
LOT tMIBEA CJ6Z5
DOSE 1 0 t1CG
PATIENT CLASS HEALTHY ADULTS
I TOTAL Vl CCIHtES I 15 P ATIENTS l - OOSE 2 I

l----------------------------------------------------------------------------1
I Dl YS POST Vl CCIHl TION I tlUt!BEA
CLINICAL
COtfPLAltlTS
l----------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I 5 I WITH
lt:OMPlAlHTS
••••••••••••••••••••••••••••••tm•••l••••••••••l.•••••••••••••••••••••l••••••••••l•••••••••• I•••••••••• ••••••••••••••••••••••
I I • I I I I I
RElCTIOH, LOCAL IJNJECT. snn I 9 • 6 • t I D I O • 0 I I 11
• f 60.0:0 • , 4 t .o;o I < n.1;O I < o . oY.1 I I o.o;o I t o.o;o I I c 73.3%J
-----------------------------------1----------•----------l----------l----------l----------l----------•----------•-----------
sOREHEss I 9 I 6 I 2 I II I o I o I I 11
I I 60.0Y.) I I 40.0Y.) I I 13 . JY.I I I 0 . 0Y.I I I 0.0Y.J I I 0 . 0Y.I I I I 71.3%)
I • I I I I I I
STIFFNESS/TIGHTNESS I 1 I O I O I O I O I O I I l
I ( 6. 7Y.J I I 0.0Y.) I ( 0.0Y.I I I 0.0Y.I I I 0.0Y.l I I II.DY.I I I I 6. 77.)
-----------------------------------l----------l----------l----------1----------1
svsnt11c I 1 I 1 I 1 I 2 I----------l----------l----------
1 I 1 I l-----------
I 3
I I 6 . 7Y.J I I 6.T/. 1 I I 6.7Y.> I I 13.37.> I I 6 . 7?.I I ( 6.7%1 I I I 20.0% J
I
!,!HOLE BODY/GENERAL l I 0 I 0 I 0 I 0 I 0 I I l
6 . 7ZI I I 0 . 0lO I c o.0lO I C o. o:o I , 0.0%1 I I 0.OY.) I I I 6.77.)
I I I I I I I
fATIGUE/NEAKNESS 1 I 0 I 0 I 0 I 0 I 0 I I l
6 . 7io I f o.o;o I 1 o.oY.> I 1 0 . 0Y.l I I o,o:o I • 0.0?.I I II 6.7%1
I I I I I I
RESPIRATORY 0 I l I l I 1 I l I l I I l
o. o;o I , 6. 77.> I1 6. Tl.I I I 6.7lO I1 6,7Y.I I ( 6.n, I I I 6.7Y. J
PHARYNGITIS I SORE Tl4ROATI I II I 1 I 1 I l I l I l I I l

0 . 0:1.1 I I 6. 7iO I C 6. Tl.) I I 6 . 71. l I I 6. 7Y. I f f 6. Tl. I I I f 6 . 7X I
I
DIGESTIVE S 'l'STEl'I I o I O I o I 1 I O I O I I l
0.0:1.1 I I 1 ,0;0 I I O,0Y.I 11 6.77.l I f o.o:o I ( 1 .0:0 I I I 6.nn
I I I I I I I
ABbOrtINAl PAINS/CA AHPS I 0 I 0 I O I 1 I O I 0 I I l
I 0.0Y.I I I I
I .CY.I I O.0Y.) I I 6 . 7%) I I 0.OY.I I I 0.OY.I I I I 6.7Y.I
I I I I I I I
DIARRHEA I o I o I o I 1 I O I o I I l
I I G.0Y.I I I 1.0%) I I O. 0Y.) I I 6. 77.) I I 0.07.J I I 0.0?.l I I I 6. 7Y.)
-----------------------------------1----------l----------l----------l----------1
PEASotlS MITH COt1PU JNTS I 9 I 6 I 3 I 2 I
----------I----------I----------I-----------
1 I l I I 11 0
I t 60.0Y.I I t '40.0l!l I C 20.0Y.I I t 13.3i0 I f 6.7Y.l I I 6.7Y.l I I I ?l. 3%1 0
0
0'-
,0
~
Table 2 (Contd)
PATIENT COUNT CLINICAL COMPLAINTS
AECOt18INANT HEPATITIS 8 VACCINE
STUDY 0779
TREATMENT
LOT N\Jf1B£R CJ625
DOSE 10 t!CG
PATIENT CLASS: HE ALlH'I' ADULTS
I TOTAL VACCltlEES I 15 PATIENTS J - DOSE 2 I

•----------------------------------------------------------------------------1
I DAYS POST VACCINATION I HU118EA
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------I
I O • 1 I 2 I 3 I 4 I S I
WITH
IC011PUINTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••1•••••••••• 1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
-----------------------------------1----------l----------l----------l----------l----------•----------•----------I-----------
PERSONS WITH HO COMPLAI NTS I 6 I 9 I 12 I 13 I 14 I 14 I I 4
I I 40. OY. J I I 60 . OY. I I I 80. OY. I I I 86. 7;0 • I 93 . 3Y. l I C 93. 37. I I I I 26. 7Y. I
-----------------------------------l----------
PERSOlS WITH NO DATA I O
l----------1----------1----------
I O I O I O
1• ----------1----------I----------I-----------
o I O I I o
I I O,OY. J I I O.OY.I I I O. OY.I I I O.OY.I I I 0 . 07.l I I 0.07.) I I I O.OY.l
0
0
...,
0
.,,
Table 2 (Contd)
PATIENT COUNT CLINICAL CottPLAIHTS

RECOt18IHAHT HEPATITIS 8 VACCINE
STUOY 0779
TREATl1£NT
LOT NlRIBER CJ625
DOSE 10 11CG
PATIENT CLASS HE ALTHY AOULTS
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES I 15 PATIENTS I - DOSE 3 I
•----------------------------------------------------------------------------1
I DAYS POST VACCINATION I N\JHBER
CLINIC AL
COHPLAJHTS
1-------------------------------------•---•----------------------------------I
• 0 I 1 I 2 • 3 • 4 I S •
WITH
ICOHPUINTS
••••••••••••••••••••••••••••••••••• l•••••••••• l•••••••••• l•••••••••• l••••••••••••••••••••• l••••••••••••••••••••• I••••••••••
I I I I I I • I
RE ACTION, LOCAL (INJECT. SITEI I 9 I 3 I 4 I 1 I 1 I l I I 11
f I 60.0Y.) I I 20.01.1 I I 26.T/.I I I 6.71.1 I I 6.77.1 I( 6.71/. 1 I I I 73 .37.I
-----------------------------------1----------1----------1----------
PAIN I O I 1 I 1
----------
o ----------
o ----------
o ---------- -----------
l
, , 0.0il.l 1, 6 . 7iO I I 6.T/.1 I 0.0Y.I I o.o;o .( o.o;o I 6.77.)
I I I
SDl'ENESS I 9 I 2 I 2 o o o 9
I c 60.01.1 I c 13.31.I I t 13.3Y.I c 0.01.1 , o.ox, 1 o.o;o , 60 . 0;0
I I I
TENDERNESS I G I 0 I l 1 1 l l
I 1 0.01.1 I 1 0.0;:1 I , 6.r1.1 t 6.11.1 , 6.77.1 , 6.nn 1 6.77.1
I I I
STIFFNESS/TlGHTN!SS I 1 I O I o O a o l
I , 6. 1;0 I t o.o;o I , 0 . 01.1 • 0.01.1 , o : o✓., , o. o;o 1 6. 1r.1
-----------------------------------1----------l----------
sysTEn ic I O I O
l----------
I l
l----------l----------•----------l----------l-----------
I l I 1 I l I I 1
Ic 0 . 01.1 Ic 0.01.1 Ic 6 . 11.1 Ic 6 . 77.1 Ic 6.11.1 Ic 6.77.1 I Ic 6.71.1
------------------------------------------------------------------------------------
1 I I I I I I
RESPIR ATORY I o I O I 1 I l I l I l I I l
0.01. 1 I I 0.0?.I I I 6 . T/.1 I I 6.7%) I I 6.7%) I ( 6 , 7?.) I I C 6.71.)
I I I I I I I
PHARYNGITIS <SORE THROAT) I O I D I 1 I 1 I l I l I I 1
I ( 0.0?.) I I 0 . 01.) I I 6 . 7XI I I 6.71.) I C 6.7%) I C 6.7?.I I I I 6 . 7½1
--- ---- ----------- -----------------1----------l----------l----------1----------I----------I----------I ----------I-----------
PERsoHS WITH CCMPLAIHTS I 9 I 3 I 4 I 2 I 2 I 2 I I 11
I I 60.01/.1 I f 20.0X) I I 26 . T/.I I l 13.JY.I I I 13.]Y.) I f 13. 37.1 I I I 73 . 31.)
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH NO COMPLAINTS I 6 I U I 11 I 13 I 13 I U I I 4
I I 40.01.J I I eo.ox, I c 73.37.1 I c 86.7:0 I t 86.7%1 I c 86.77.1 I I c 26 . 71.1
-----------------------------------1I----------l----------1
PERSOHS WITH NO DATA o I o I----------I----------I
o I O I----------I----------I----------I-----------
o I o I I o
I I 0.0XI I I 0 . 0XJ I I 0.07.I I I O.OY.I I I 0.0%1 I I 0.07.I I I c O. O½I
0
0
.:>
....
--
Table 3
PATIENT COUHT "AXlt1'Jt1 TEt1PER AT\J11ES
RECOHSINANT HEPATITIS B VACCINE
STUOY 0779
TREATHENT
lOT tlUMBER CJ625
DOSE 10 ttCG
PATIENT CLASS HEAlTHT ADUlTS
I TOTAL VACCINEES C 15 PATIENTS I - DOSE 1 I

1I---------------------------------------------------------------------------------------•
DAYS POST VACCINATION • NUl'18ER
MAX TEMPERATURE
I DEG F • ORAL I
•---------------------------------------------------------------------------------------1
I O • 1 I 2 • 3 I 4 I 5 • •
WITH
I HAX TEHP
••••••••••••••••••••••••·••••••••••·•••••••••••••••••••••I•••••••••••••••••••• ••••••••••·•••••••••••••••••••••I••••••••••
• I
< 99 I 10 I 13 I 14 I 13 14 12 I • 10
66.77.) I I 86.T/.J I C 93.3i0 • C 86.71.) 1100.0%) C 85.77.) I • C l,6.71.)
I I I • •
'19 - 99. 9 • 3 • l • l • 2 O 2 • I 2
20,0iO I C 6,T/.1 • C 6.7XJ I C 13.31.) I o.o;o I 14 . 3)0 I • I 13.liO
• I I I •
100 - 100.9 I l I l • o • o o o • • 2
6. 71.1 I I 6. Tl.I • C o.o:o • I 0.01.1 t o.o:o I 11.0:0 I I I 13.31.1
I I • I I
101 - 101 . 9 I 1 I o • o • o o o I I 1
I 1 6.71.J I c 0.01.1 I c 0.01.1 I c 0.01.1 c o.o:o , o.ox1 I I , 6.n,
------------------------l---------~1----------1----------1----------•·---------l----------•---------------------I-----------
TEttPEIIATUIIE TAK EH I 15 I 15 • 15 I l5 I 14 I 14 • • 15
• 1100.0:0 I 1100.0:0 • 1100.01.1 • 1100.0:0 I I 91.31.l I I •J.37.1 I I 1100 . 01.1
------------------------l----------
TEt1PERATURE NOT TAKEN • 0
l----------l----------l----------l----------•----------•---------------------I-----------
I O • O • 0 I 1 I 1 I I O
I l O.OiO I C O.OZI I C O.OZI • I O.OZI I ( 6.7)0 I I 6 . 77.) I I I o.o;o
0
0
0
"'
IV
,,,
Table 3 (Contd)
PATIENT COUNT HAXItlUH TEHPERA~ES
RECOl1BINANT HEPATITIS B VACCINE
ST\JOY 0779
TRHTMEHT
LOT Nl.lmER CJ625
DOSE 10 ttCG
PAHEHT ct•ss HE ALTHY ADULTS
I TOTAL VACCINEES I 15 PATIEHTSI - DOSE 2 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I HU118ER
HAX TEHPERATURE
t DEG F, OllA LI
1---------------------------------------------------------------------------------------I
I II I l I 2 I l I 4 I 5 I I
WI TH
I tlAX lEtlP
••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••• l•••••••••• l•••••••••• l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 I n I 15 I 14 I 12 I n I 12 I I 11
I t e t..1x1 I n110.0;1.1 I t 93,3,:1 I c ,2.1;0 I t 9z,9;,:1 I t ,z . 31.1 I I c n.3;,:1
I I I I I I I I
99 - 99. 9 I 2 I o I 1 I o I l I 1 I I l
I c IJ.37.1 I c 0.0;,:1 I c 6.77.1 I c 11.11?.1 I I 7 . 17.J I 1 7.7?.J I I c 20.ox1
I I I I I I I I
101 - 101. 9 I o I o I II I 1 I o I II I I l
I c o.ox, I I o.o;o I , o. or.1 I 1 1.1i:1 I c 0 . 11,:, I , o.o;o I I 1 6.n ,
------------------------l----------l----------l----------l----------l----------l----------l---------------------l-----------
n11PERATURE TAKEN I 15 I 15 I 15 I 1l I l<, I 13 I I 15
I 11110.UXI I 1100.0?.I I 1100.0iO I I 86.Tl.l I I '13,3i0 I I 86.7?.I I I 1100 . 0;0
------------------------l----------l----------l----------l----------l----------l----------l---------------------l-----------
n11PERATURE NOT TAKEN I o I o I o I 2 I 1 I z I I o
I C 11.0?.I I I 0.07.) I C 0.07.) I C 13.37.1 I C f> . 77.1 I I 13.3?.I I I I a.or.,
0
0
_,
Q
""
·•
Table 3 (Contd)
PATIENT COUNT HAXlt1Utt TEHPER AT\/RES
RECotlBIHANT HEPATITIS 8 VACClll'E
STUDY 0779
TRUTMENT
LOT HUl1BER CJf.25
DOSE 10 t!CG
PA.TIEITT CL ASS KEAL TKY ADULTS
I TOTAl VACCINEES C 15 PATIENTS) - DOSE 3 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATIOII I NUMBER
t1111X TEMPERATURE
IDEG F, ORALI
1---------------------------------------------------------------------------------------I
I O I I I 2 I 3 I It I 5 I I
WITH
I MAX TEMP
---~···~···················••A••········•*···· .................... ········••I••········
I ······••M•l••····~·•• I••········
HORMAL I 2 I 2 2 2 2 I 2 I 2
13.37.) I I 13 . llO I 13.3)0 C 13.37.1 C 15.47.I I I 13 . 37.1 I I 13.37.1
I I I
<'19 I 13 I n n n 9 I 12 I 11
86.77.1 I I 116 . 77.1 I 86.T/.l ( 116.77.I C 69.z;o 11 110.07.1 I I 71 . 37.1
I I I
99 - 99. 9 I II I Cl 0 Cl l I l I 1
11.07.1 I I O.OY.I I 0.07. 1 I o.o;o C 7 . 7)!1 I I 6 . 77.) I I 6.T/.1
I I I
1 01 - 10 1. 'I I o I o o o 1 I o I l
I c 0.07.1 I I o.oY.> I c o.o;o I c o . o;o c 7. n, I I o . 07.> I 1 6. 77. 1
------------------------1----------1----------1
TEHPERAME TAKEN I 15 I 15 I----------15
I----------I----------I----------
I 15 I 13 I 15 I---------------------I-----------
I I 15
I 1100.07.1 I 11 00 . 07. 1 I 1100 . ox> I 1100.07.1 I t 86.77.l I 1100 . or.1 I I 1100 . 07. 1
------------------------I----------I----------
TEl1PER ATURE NOT TAKEH I O I 0
I----------I----------I----------I----------
I 0 I 0 I 2 I 0
I---------------------I-----------
I I 0
I I 0 .07.1 I I 0.07. l I t o.07.l I I 0.07.1 I I ll . 37.1 I I 0.07.J I It 0 . 07.1
0
0
....,
C>
.s:.
-
00075
Edward M. Scolnick. Arlene A. Mclean,

David J. West, Jules L. Oienstag.
Eloise Watkins, Friedrich Deinhardt and Wolf gang Jilg
23
Antibody ind Clinicail Responses Among Healthy
Adults to a Hepatitis B Vaccine Made by
Recombinant DNA
Cum:ntly, all c:ommerc:ial hepatitis B vaccines are comprised of HBsAg purified

from the plasma or human carrien or the vin1s. However, the use of recombinant
DNA technology to effect synthesis of surface antiaen by a culture or microorpn-
isms is an am-active alternative to infected human plasma as a source of HBsA&
for vaccine. Good expression of the 1ene for HBsA1 has been effected in yeast
(/).
Recently, Mtiaen purified from fermentation cultures of a recombinant strain
of the yeast, Saccharomyces cerevisiae cont.a.inins the gene for the adw subtype
of HBsAci was formulated into a vaccine throuah absorption on alum adjuvant.
Two methods were utilized for the purification of the HBsA1. lmmunc affinity
chromatography uses specific antigen-antibody bindi~I to effect purification, while
the second method, hydrophobic intc?Ktion chromatop-aphy followed by gel
exclusion chromatolf'aphy, depends upon the selection of water-immiscible mol-
ecules followed by separaaion on the basis of molecular size.
The physiul and chemical characteristics of vaccine made from HBsAg pro-
duced in yeast are very similar to those of vaccine prepared with HBsAg purified
from human pluma. Furthermore, the yeast recombinant hepatitis B vt.ecine has
been shown to be both immunC)IJenic z.nd protective in animals (2).
We report here the clinical 11'.nd antibody responses obtained in the first three
human clinical studies of the yeast recombinant nccine involvin& a total of IOI
VIRAL HEPATTTIS end LIVER DISEASE Cop\,righl @ 1 bv GNno Is Stninon

158N G,8081.117" All rights ol rep,gduc:licn in any form relSfYGd.
Sto1n1c~ E~. rkl n • ~st OJ, 01 n$Ul0 JL. thin$ E. DQ1nhardt f.

nd clifiiC 1 FG$pcns $ ~ ~ ~lthy dult$ to hp titis B
~ cc1~ d by roe in nt D~. In: ~r i ~. Di nit&~ JL, Hoofn glQ JH.
Gd$. V1r&1 HaPQtit1z &~d Livor D1ss i • Orl~ft~@:&f't!lno oo Str tton, 1984:
315-17.
00076
3l6 Sc:olnick. Mclean, West. et al
vaccinees. Participants were healthy, nonpregnant. adult volunteers. At entry,

subjects were neptive for all hepatitis B serologic markers, had a nonnal ALT
level, and had not received any olher hepatitis B vaccine.
Partic;panLS in lhe studies received a 1.0-ml intramuscular irtjection or the
yeast recombinant hepatitis vaccine containing JO ..., of HBsA1 at 0, I and 6
months. The veccine used was from one of two lots. (Lot 93-' prepared by the
immune affinity chromato8f'aphy melhod and Lot 972 prepared by the hydrophobic
interaction chromatography method.} Vaccinees were asked to record lheir tem-
perature d1.1ly for S days after each irvection of vaccine and to repon any loc:al or
systemic: reactions that occurTed during that period.
Postvaccination blood samples were taken for the determination of hepatitis
B serologic markers z.nd ALT. In addition, 11 radioimmunoassay for the detection
of antibody to anti1ens in an · extract of yeast lacking the gene for HBsA& was
applied to pre- and postvaccin&tion umples.
The vaccine was well tolerated. There have been no serious adverse effects
attnoutzble to vaccine and no evidence of hepatitis B infection amonc the vaccinec:s
(i.e., no elevation of ALT and no anti,lenemia). Local reactions consisting prin-
cipally of mild soreness at the iqjection site, senerally lasting 1-2 days, have been
reponed following 20%--80% of iqjections with vaccine purified by the immune
affinity cbromatosraphy method (Lot 9~} and 169'--2S9fi ofinjec:tions with vaccine
purified by lhe hydrophobic interaction chromato,rapby method. Systemic com-
plaints including fatigue, headache, elevated temperature (1019 F-102" F, oral),
pstrointestinal disturbance, symptoms of upper respiratory infection and nose-
bleed have been reponed followin14~33~ of injections (Table 23.1 ). There have
been no sisnificant increases in antibody to antigens in yezist extract associated
with vaccination.
Table 23.1
Clinical Responses emons Healthy Adults to 10 .,.g Doses of
Recombinant Hepatitis B Vaccine Administered at 0, I and 6
Months
Proponioa (~) of VM:cinec1 with Clinical Complaints
within S Days of Vaccination
Study C Vaccine Lot Site Dose I(~) Dose?(~) Dose J (~)
m 93'! LOC&1 12/15 (IO) ll/Jj (73) I 1/15 (73)
Systemic S/1.S (33) l/1.S (20) I/IS (7)
m Local 6124(15) l/19 (16)
Systemic 1/24 (4) 3/19 (16)
ffl 934 Local 19128 (68) I 1/28 (39)
Sys1emic 5/21 (18) 41:?8 (14)
795 934 Local Sl"..5 (20) 6119 (32)
Systemic: S/25 (20) 1/19 (5)
'
00077
HBV \l.iccine Made by A.combin.int ONA 317
Table2J.2
Seroconversion Frequencies ror Anti-HBs among Healthy Adults
Receivins 10 11,g Doses of llecombinant Hepatitis B Vaccine Bl o. l
and6Monr.hs
Pros,onion (~) of Vaccinees with Antibody
Study ts Vaceine Lot C I Mo. lMo. 3Mo. 6Mo. 7Mo.
779 934 6115 14/1.5 1.5115 l.5'/15 14114
(40) (93) (100) (100) (100)
972 7124 13/19 ll/14'
(29) (61) (86)
792 934 11121 21/23 13113
(39) (91) (100)
195 934 l/30 21/30 19/22
(21) (70) (86)
Antibody responses to 10 1,1,1 doses of

the yeast recombinant vaccine have
been comparable to those observed in previous studies with 20 f1,S doses ofvac:cine
prepared from plasma-derived HBsAg. At I month, 2 7 ~ of the vac:c:inees
were positive for anti-HBs. By 2 months, 68%-93% of the vaccinees had anti-
HBs, and at 3 months 86%-100% were antibody positive (Table 23.2). The third
dose of vac:dne at 6 months bas been given to 15 penons in one of the studies.
resulting in a mon: than 25-fold inc:rea.se in 1eometric: mean titer.
REFERENCES
I. Valenzuebl P, MediM A, Rutter WI, euJ. Synthesiund usembly of hepatitis B virus

surface antiaen pmnicles in yeast. Nature 1911; 291:347-350.
2. McAleer WI, Buyn&k EB. M&ligener R,Z, et £1. HWN\11 hepatitis B vaccine (rom
recombwlnt )'CIISl. N hire 1984; 307: 171--180.
00078
/botrmrxl-lloJoum::/ fll lla.MEricotl;b1lcc/_,

...., ,. •-· -a•
~ la:14, - ~ -
Original Contributions
Clinical .Evaluation in Healthy Adults of a

Hepatitis B Vaccine Made by Recombinant DNA
Edward M. Scolnick, MO; Ariane A. Meleen, PhD; David J. West, PhD; William J. McAleer, PhD;
Willia m J. Miner, MS; Eugene B. Bvyn k, PhD.
A vec;c;ln formulated from hepalltl 8 surface anUgen (HB11l9) Since there is no ·,trective treat•
produced by recombinant ut111ln or the ye11at S•ccNiromyc•• cerevlmo meat for hep titia B infection. pre•
w1111 administer d to t wo group of hum11n volunte rs compoaed of 37 veation i1 essential. A safe, effective
hea lthy, low•rlak 11dult11. Each sUb~ct recel¥Od a 10-,ag dooe of HBaAg Ill 0, 1, bum&11 hepatitis B vaccine is now
11 nd I montha. By on month, 27% to 40% of the vecclneee Md anUbody to available. Hown-er, it utilizes bep&ti•
HBaA9, and by three month11 80% to 100'!& w11re anUbodJ poalU• . Lerge tia B surface a ntigen (HBaAr ) puri-
boo••• In mer followed t~ ·tN,d dos at 111 months. TIie anUl>OdY formed hi _lied from the plum& of h11m111 carTi•
predomlnanllJ specific for the> • dcil rmlMnl of HB11Ag. TII re been no "'1•• ers of hepatitis B virus ia!ection.
11ertoue roactlon11 «i ttrlbut b l to the vaccine. TIIC> mo t frequent complaint Consequently, the supply of vaccine is
has b een transient 11orenG>e11 at th Infection elto. A11 far as we know, lhle 10 potentially limited by available
th first repc,rt d u@e In ffll!ln ot a v ccln prepered by recombinant DNA sources o! 111itable plasma. In addi-
t echnology. tion, extensive processing a nd safety
(JAMA 19M;251:2812·2815) testing lwve beta DICISSlry to ensure
production of a vaccine anti1en that
is PllrG ud free o! r.ny extraneou1
WORLDWIDE, humAJl hcapatiti B chrollic carriers now estimated to living agent that mirht have been
infection coutitutes a major public number 111ore than 200 million.' Inlec:• preunt in the ,tarting pluma. Even
health problem. In addition to the tion i11 traumitted to sasc:aptible per· thour h multiple inactivation treat•
disability auoeiated wi,h acute elin.i• ·· sons throul'h contact with the blood, menta uMd in the antieen purific:a•
ca l diseue, chronic liver dituu, cir• temen, or win or chronic carriers or tion procea han been shown to inac•
rhosis, and primary hepatoc8lluw persona 11lfferi.ng acute lnlectioc. l11 tivate repruentnti'fU of all major
carcinoma are now rec:oguised ~ue- low-incidence co11atrin, 111c:h as tht ,rroupo of a nimal viruses,' concern
lae oC lll1NSOl•ld bepl!ltitu! B in• Ullited Statn, the risk ol he~titit B over the theoretical po1sibility of a
infection is 11till lii1h amonr certain lirin, orpaiem s uch u the etioloric
See 111110 p 2765. rroup of health care personnel, arent of acquired immune deficiency
patieau receiving dinlysis tnatments S)-ndrome beinr present in plasma
fection. Indeed, ill eomt ue ol or blood productl made from ~ and s urviving th, purification and
Asi& and 1ub-Sakaraa Africn, pri• pools, children born &o Alukan Eski- inactivation procedures ha, slo11,ed
ma ry hepatocellular carcinom ooten- mos or to Indochinese or Haitian acceptance of hepatitis B vaccine.
sibly attributable to hepatitis B infec- refuceea, residents oC iMtitutions for A promi11in1 alternative to inrecttd
tion ra1Dks as II leading cau11c of the mentally handicapped, prisoners, humllD pl11.1m11 u • source or HBsAg
~ncer deaths r.mon me.I ' usen of illicit inject ble drugs, and ror Yraeciae Ul the use or recombinant
The reurvoir ol hepatitis B viruo persona ·ho ere saxuolly very pro- DNA technolOf!Y to effed synthesis ol
resides m ainly in LI population of miacuous.1 In high-incidence rea11 the tmrl ce antigen b)' a culture or
euch u South111ut A.sin, tranomiu ion microotgADisms. The hep:ititis B vi•
______ ,..._
f,- 1110 a.ell
Aooc,e,cll. ~ ~ ' ~ ~
INllilll:lO 1P Dcs:::ii=
l.ebro-
from mother to child in the perinatml
period ia the m jor mode oC infection
rus gene coding for HBsAe has been
cloned both in EacJarrid1.ia coli a nd in
siupplemented by horixonul tnno- y.tut►'; however, expreS$iOn of the
Rop,vt1 le Mc:,cll ~ ~
" C ~. - ~ r , l l C - minoion b2twoen ollu~r f mily con• gene in yeast has bP.en much better
~o-, W- ...... PA I (D, . . . _ ,, , tacts.' th n in E coli. Furthermore, HB3Ag
281a JAMA. Juno 1, 1964-Vol 25 I, No. 21 Hopolitil! B \fac;Cln<il- Sc;olr\tc;lt el al

produced by recombinn11t yeast cells COOIODt WOI obtai11ed after proriding ~ch milli1111it.s per milliliter usinc tho form11la-
has been shown to aanptc! into partic.ipu,t with iAlon1U11ion on the aourm tio11 described by Holli111er et &I." A.
particll!S closely resembling th~ iso- or Iha in.,estigatiolUll yeast ,,_mbiaaat Mrum sample G'U coasidertil positive !or
lated from human plum.a, and this hepgtiti, B •accine, animal tetlt nsultsi nnti-HB. if the ruio of th• sample co11nts
material wu 1ho1V11 to include anti- obtainod .-ith tho vaccine, •acciution ud per miouta to tho negative col\tl'OI serum
bodies in mict and guinea ·pigs.u bleeding achedulea, &nd the potaati&! risb cou11ts per m.ioule vu 2.1 or cr-ater.
a.nc! bene6u of partic.ipatioo in the stlady. Esti111ata or the proportion oC uti-HB1
Recently, antigen puriied from fer-
. i11 postnccinatioo sera sc,ecilic for tu ci
mentation cultures of II reeombiunt VaccJn or 4 deter111inaata of HBaA1 wen baaed oo
strain of the yeast SaccAcst'O!Ryca an . . .,. dnalbed by Hoofnagle et al."
c~" containing the pne for
Hepatitis B IIUf&c:11 &11tig111 for tho
•acciDe wu produced io t,rmeol&tiOa CW· Briefly, aliquobl of eacb serum sample are
H~1Ag has been formulated in.to n tu11111 of 11 ,._mbiaant straia of the )'Ullt i111:ubatecl wid1 a aub'Yi" a,d HB,Ac·
vaccine through adsorption on alum S Cltn7VimiAo a111tainiD11 a plasmid earryillg positiwe Ml'll.111. with a subtype 4¥ HB,Ag-
adjuv&!lt. Electron microncopy re- tho s-1111 (or the 14v 1ubtne of RB.Ac. u positi\"e serum. and with oormaJ hu11111n
veals th&1t the purified HBaAg ased dftcribed prnioualy.'.,. Mrum for t.i, houn at room temperanare,
!or this YIICCine wtl u ~ t e ho 11111tb9cb ..,.r,i emplo,ed for tbo aad thu nch milttllre ill carried through &
particles 20 to 22 nm in diameter, 11 purification · of HllaA1. lmmuu &mnity 1t&Ddnrd radioirnmu11oauey to measure
chl'llllla&.osrapbf 11HS slJ8Cille mdcoD• ruidual uti-HBL Baaed oo the ~:-cut ot
morpholoCY also cnaraetcristic of free Deutralization with the two HBaA.c sob-
1ur!ace antigen ill mfKted plum uu'body bindi111 to deet pari&catio11,
•hilo tho 1ea111d mttllod, b)'dropbooie tn,e sera when eompared with the 11Aoeu-
and of the J)U.rifled 1U1tiae11 ll0'7 oaed b'alited normal h1unu Mnim. an Ktimal.CI
iat.racuon cbromatotra11h1 followed by
in plasmn-derived hepatitie B necine. c:&11 be made of tilt nlative &111ouota of
Ill czchaliDD darolD&t.Oll'l,plly, UIIIDIU o■
In contrut to HBsAr from luamu 1elfflioo of water-imlllilcil,le molecwee uti-a and anti-cf utibodi• present. Since
plasma, the an~n produced by follow.I by separatioa by iaolecu1ar lisa. the YamDt ifl a mOIIOV&lHt•type adao
recombinant yeast is not r!yeosJ• Detaila of UM •1111raai11 oC HBaA1 ia preparation, MR will C:ODWD titur uti-cf
lated. Under reducinr conditiou. so- 7'1&11t ud tho puriAcadoe el tho lllnllCQ antibod-, uti-o aatibodia, or a aimbi-
dium dodeeyl sulfate tlectropbornu, antipa will be puhll1htd 11Mw.bere. Pwi- D&tiOII or botli t:n,es, ud the amount of
of the utigen purified from yeast 6ed HBIA1 wu tttat.ld witll {onnalclo- neutraliution with the HBIA1-cv MrUm
hyce t.o stabilize the material ud t.o lrill ie tllerefon a direct uuy for the 11110G11t
rtYIAlt ll 1ingle band of anolllClllar
a111 atranNU li'l'UII IIQUI that might ot anti◄ prt1t11L Subtnctiog the amoaat
weight 23,000, which corNGpoDdl to
the nonglyCOl)i&ted polypeptide that bo preeeaL TIit 1.11tip1 wu tlwa fonau- . ot lltllltrali&atioa wiib the RBIA.1-c1/
lated iato a vacci11e through adaorplioe oa aenam fn,m that foulld for tbe HBIAf-ad
is tbe major compoa111t of the hepati- MrVm thn si"8 u nti111&te oC the
alum adj11Yllllt t.o riww 10 ,c of HIIIIAI aad
tis B Yirus envelope. The nccine U 111g of alumia11m (1i)'drollilh) per 1-1. amount oC anti-c prnaoL
formulaud using this material bu dooo. Tho &nal formulation alao c,oot.a.ioed A radioimauaaoauay wru developed to
now been 1howa to be immunog1nic 1:20,000 tllimel'llllll u a praervatiYa. Vac- cleuet :,east anti'bodin io the aera of
for mice and for monkeys with a cine wu mailltaiaed at 2 t.o I •c otil vaccine recipielita. For this assay, 111
potency equal to or superior to that of lllOd. enract ol the parnt 1trai11 of S ~
vaccine made from plasma-derived lacluq the plumid contawnc the ,enc
Proc:•durea for HBaAg WU prtparecl by di1nipti11c I
antiren. ID addition, chimpaa&ea im•
60'1, 1111penaion of the cellt ia a homor-
munized with this yeast recombinant A blood ample wu obcaiaed from eacb aiur and the11 clarilltd by ceotrilucation
hepatitis B vaccine (HBaAg subtype 111bject approzimat.lJ tvo WNb priol' to at 9.000 r followed by pauaa, thro11ch a
ad111) were fully protected whon cbal• tile Int ncclaatioa aad wu tat.Id for 0.'5-m,im membrane 61tar. The clarified,
lenf'(i with virus of either type adr or HleA1, antibody lo HBIAs (aoti-HB.), tlhend lltV'Ut was dilu\ed ta • final
GlfU', while unirnmuniud aD.imala all antibody t.o eon antisn (uti-HBc), ela- protaia fODCtlltrat.ioa of 80 111/ml. with 0.1
Diat aminoi.nuferase IALT>, aad JeU& M carbonate buffer aad pH 9.6 and
showed evidence of infection when
antibody. Subjeetll fouad elirible on t!MI adsorbed to 14 •in pol71tyrt11e beads o•tr•
challtolf'(l.'"
buie of &h"8 UlaJI were ldlldultd t.o Difht at ' •c. Wuhed, dried beads Wttt
In this article - describe N&Ulta of rcaivc II U-mL (10..llfl KBtAg) latrama- maintained Dt -20 •c. T•·o hundrtd-
the &rat human immUDOpnicity•
safety trial of tho yuat reeombinaat
aalar injec:tioa ol the 11111t l"ICOmbiuat
ncciao at 0, I, and I montl!a. Postvacciaa•
microliur "'°'""'" of 11ra diluted 1:100,
1:1,000, and 1:10,000 in pboaphate-bul'l'ered
hepatitis B vaccine. To the beat ol our tioo blood mmpl• for tilt detar&iaatio11 aaJine eo11t.a.iai111 0.5'.Si bovine senim albu•
lcnowled,e, this is the &l'lt time th t of hepatitia 8 1tn1logical markffl, ALT, min and O.H, TwHn 20 were incubated
a vaccine prepand by ncoinbinant 1111cl yeut 1111tibodr were ICMC!ulod month• with eootecl bead11 for three \ours at !7 •c.
DNA t.echnolao hu b.i&n 11sed in Jy {Of IQYOD DIOIIUII Hd at 9, 12, atld 2.4 Followin1 thl'ff wuhes with water, · tht
m II. months followin1 the llrst iajtetien.. bads Wffll i11cubatecl with 200 ,,.L of iodine
Vaccinffll .-ero asked to take their t.111• 125 protein A (1pecific acti•itr, 100,000
perature daily for 6¥t da19 after each c:pm) for U houn at 37 •c. The protein A
MATERIALS AND METHODS
injtttion of vaccine and t.o report any 1-1 binds and labials any anliyust antibod>· on
Poput&tlon or l)'lltoll\ic rcmetioDG that might occur Ult bQad t~ is of the IeG class. Aft.er
ParticiP411t.11 in this suady ft! lionlthy, during thia period. threo .additional w,11,tor wuhes, the beads
nonpAff1111Dt &duh emplo)'OC!G of Mord! 'l:tert CRllltad and tit.rs of y1ut antibody
Aomeyt:1 WINI dtttrmintd by interpol11tion from 11
and Co. Inc. SubjON had to bo IIO(IOti
for hepntitio B serol~cal 1nnrktl'II lid Standard radioimmunCN16111ly lallt kitll 11t..1111dard c11rve derived uaing dilution, o( a
have n normal km1l of aluino lllllino- "'Q ro uaad for lho determi n11tion of lin,erimmuu ruinea pi1 serum havin11 an
tre.nsraraao and mus& not hnvci rocoivad HBeAg, nti-HBn, and anti•Hk TitorD ot 11n1ibody titer to porent yeast extract or 1
nny other hepati&ia B 111lcci110. Writta11 anti-HBo 1>1oro o.1prt11Jlld in internntioruu million.
JAMA, .Jw,,o I, 19G4-VOI 2!1, l'do. 21 Hopotitio 8 V11ccino-Scolnick ol 111 2813

OOOAO
The Silrum samples of vnecinttOll woN>

Tablc:i 1. -Propo,tian ('Ill) of VoccinQoa Wrth Clniail ~•inta Dutinv o
also meas11rGd (or changes in preuistinR
Fi•o-Oay Period Following lnjQclion of Yanot RIICOfflbina"t Hepatitis e Vaecine
specilit yeut aacibodia or the app,211nace
of nev 7tast 1U1tibndiesi uia« a eodi11m Voccao Lot No. DoGo 1 Dooo 2 Do.• J
dodecyl t11Ua111 polJ11UYlamide gel electro- S..-aa 11 noclion MO
phoraia (redlJCin1), WIIISien blot tech·
aique. I.a this p,-dun, pnront yea.at ,.,.,.,_...........,.
enract is ael)Gnlted oa 11 12.5 poly-
acrybun.ide gal Alter tnuftr to a nitro-
cellulose ahae1t. polypeptiden fn,rn th, gel
· - . . . . , . , . _ w:111 ..., ., _,, . , . . . _ o1 111o toeo,,;,,g: ...,_......,_ :ia.3 "' :ieJ1 ·c 1,0, "'
■ 111 detectod by inaab11tioa vith 11 1:50

,02 "I') <->. IDIIOUO ~>. po•- diolufbeftco lkMl. -Cllo (five). ,.,.,..,._. or -
__,,.WY tract - - 1 - ). - - (ono), ·
dilution of the •accio1e'1 Mna.m, followed
by iacubecio11 with •1 pro&eia A. a1ul
upoaure to 1-ray llm (T. Mnto11, PhD, Tat,io 2.-Setoconvoraiotl Freque,ncic,a and C.-tric Mean Tlte,a (GMTt)'
oral com111uaicatioa, 1982). lot Anli-Hlla Among lnitially S.,anogali,,e HHllhy Adullll AeceMng I o-.,g
0oe0o ol Yeoat R ~ Heoolilill B Vaccinot
RESULTS
The vac:c:irle has *D woll tolerated.
None of the 37 aubjeeto studied to
date hu experienced a teriou11 ad-
ver,e effect attn1,utable to fllCCine.
There has been ao evidence of hepati-
tis B infection amo111 necine1111, ie, no
elevation of ALT n.lua and no aati-
genemie.. Mild 10re11est1 at the injee,.
tioa site pntra.lly lasting one to two
days wu reported by 731. to BOll, of
vaccineet who received vaccin purl•
fied by immune aftinity chro~togra-
pby {lot 934) bat by a substantially
~-....., ,,a
(lt,....,olirc . . . . . . . .
..,.....,._,.....,.,.,,,llli!iiib.
t/110, 1 , e n l l l t -
tt
smaller proportioa-2011, to 2'tJ.-of ..... - ........ - IIIOII> cl ..... - O.& ....Ultftl - a...,..i a _,., Gf 0.3 lfflU/MI. lat
subjecta who received vaccine pre- call»!I.,. Ollfa.
pared br h)·dropbobic: interaction
chromatocraphy (lot 972) (Table 1). Talllct 3.-Po,ce,\111(1811 of Anti•HBII SC>ecifiC IOr ll 811d d Oeterminanll
In!requeat 1yaumic: complaiata oc• ol HBaAcr in Poah-accinalian Sore•
currinr within a five-day period fol-
lowin1 vucioatioo have included ele-
vated temperature (38.3 to 38.8 •c
[101 to 102 "Fl ora.l), fati,ue, head-
ache, autrointestinal disturbance,
symptom• of upper respiratory t.rac:t
infection, and nosebleed.
Table 2 ,ummari:ces OW' obaerva•
tions to date on the hlllll&D immu.ao-
renicity of yeut recombiuat hepati-
tis B vaccine. Fifteen persons (tu
men, fiWl men; q!il r11J180o 23 to
53 years; mediu a,e, 33 :,ean) la&ve
.,....,eono °""' .,.._ ~...,..... ... _..._ __ 21 niU,1111... _ . . .
received all three doeu of lot 134

vaccine prepared by tho immune Twenty-two aubjecta have received at three month11. Geometric mean
&ffioity chrom torr&Phf method. YllCCi11e from lot 972 made fl'OID titenJ within lhe first thrte months of
Forty ~rcent lwl & detacttlble titer HBaA puri&ed by the hydrophobic rollow-up were similar to thon
of anti-HBs within one month of intraction chromatocr phy method. obsened amon recipients of lot 9~
receiving the first dose. By two ThlH vacci1111111 hue not beea fol- Yac:cine.
months, the proportion of aerocoll• lowed up for u long u the lot 93,& PoatvllCCin11tion serum samples
verter11 rOSle to 93%, &nd &t three recipionta, and nono has yet received with anti-H& titers ol 25 lmU/mL or
months, all rtcipieau of thill "llccini. a third dOSI!. Preliminary oorological gnat.er were asaayed to determine
v.·ere antibody poait.ive. The geometric results are shown in Tnbl12 2 for 15 of the petcen e of antibody sp~cific
menn titer following primuy immu• theoo volunteers (12 m12n, three for the -a
1111d d determinants of
niution reached a platenu nt four women; age rnng12, 24 to 63 yurs; HBsAg. Table 3 shows the results of
montha, then incrensed more th n median !life, -40 years). The P'!rcentago thae nsaays. Antibody specific for
~fold following the booster doDi llt of seroconverter9 ,,.. a 271i nt one the ca determinant predominates . In
six month11. month, 67% et two months. and SO% the interval from two to 5even
21114 JAMA, Jvno I, 1e64-VOl 2$1, e.lo. 21 Hopolilio 8 Viiccino-Scoln,c~ et al

00081
months following the fil"St dose o( no ch .. nre in the yeast antibody pat- is associated with vaccine-induced
vaccine, anti-a antibody accounted for tern for any person as compared with anti-HBs.'..c Furthermore, one 0£
approximatel}• 90~ or the total anti- his prevaccination pattern. There has these trials demonstrated that aciti-
HBs. been no a ppearance of new antibodies body Conned in response to ,·accine of
Earlier studies (unpublished) i11 postvaccination sera a nd 110 signifi- HBsAg subtype tui provided cross•
showed that the yeast recombinant cant increl!lts in the intensity of protection acainst infection caused by
hepatiti5 B vaccine induced a predom· txistincr antibody bands. heterolorous virus of subtype a11."
inantly anti• form o! anti-HB1 in Since the antibody formed b>· reci-p-
CONCLUSIONS
African green monkeys 11.nd tlwt ients or the yeut recombinant hepati-
these antibodiet1 ha,·e persisted The results of this study indicate tis B vaccine it predominantly anti-a,
throt1gh two years of follo,.--up. that a.n a lum-adsorbed hepatitis B this vaccine should be protective
Analysis of serum samples Crom vaccine !ormula ted u1in1 HBsA1 or against all hepatitis B virus subtypes.
participants in this study has re- subt)'PO IMlw ll"llthesiud by recombi- The efficac}' of the yeast vaccine
vealed no significant postvllccination nant yea.st cel111 is aale and immuno- against both homologous ad. and het-
increues in yeut e.ntibody titers u p;enic (or man. Seroconveraion · rates erolopu1 4V -rirus challenge in chim-
meuured by radioimmunoauay. By and titers of anti-HBt obtained with panzees hu been demonstrated ...
Wesurn blot a nalysis, each human the yeut recombinant vacdne in t.'iia StudiH an under ~ar to a.s,;ess
serum sample ahon a unique "fin- study are compara ble with thoae antibody persistence a nd to deter-
rerprint" spectrum or
antibodies to obie"ed in earlier studi1t1 of healthy mine optimai doses oi the reast
yeast components. There lll!IY b'1 only adults uling Y&eeine derind from recombinant hepatitis B vaccine for
a Cew or as many u 20 different human plunin....,., both healthy and immunocompro-
bands present. Aulynifl of monthly Previ0111 swdies with hepatitis B miaed adults and children.
postvaccination serum samples from va ccine ·or human plasma origin
participants in this study hu shown showed that protection from infection
Aefe,-eo
1. Frucia DP: Solaeli.., pnaar, llftltll can: . £,tp,..... ct upacltia a riru •rf. . ucitn H. Knapu S. Koll-, H1' Jr, Da...i.ea :W, et
SUl!efl\el Cor control ot·di- ia 0.0 cl,m,lop-ill y eaa&. , , ; ~ Anu a. lta-,11:fle5-17a al: hnmallOlftic lit:et of iUCLiYatecl -,acitis B
ia(f • Dtld: Ill Hepatliio I 'ril'IIII u4 l18 ralaced
di- . An /flied Die lta;S:m-m.
9. Mi)'Ufllara 4, Teiw A. Nwalli C. et at
~ ti llepa&itie I 9lll'f.lell aatlc!H ..
~ - C-p&tiM& o( Ill •icfocr&•
aiaagna . _ J II• .,-,,.. 1 l;l:Ut-Ul.
ud 40
t. Cutt I: c......,;-, s1 tho tpiN•ioloaJ •f la,-.,.&. P- J,:-,J A,.. Sci USA 1111;111:l-6. 11. Hilleua MR, la,■ak El. Jlc.1.leor WJ. tt
~cicil A aa4 I. ia s - - W, A.liar Hl, 10. Mc.AleOt WI, lu}'llk EB. YIUI"- 1%. et al: Hopuilia A 111d i.e,.utia I •acci- la
Ma)"IWCI JE (Ida): Vi,w Hr,atiN. Plliladelpllia, al: Hu111U llePGciti8 a QCCiao rn111 ,-binut Sui._ W, AIUt HJ. JGarurd J£ ltd•~ ViP'Dl
FraalJia lnti111u Pnu. 1912, pp 19-14 ,-uL ,...,_ 1Nd07:171-IIO. H ~ Plulullpkia. Fruidi11 lanitu111
1. l111111uaiaa1ioa l'racPCIII AdwiMtT Cooamit• tl . H•IUIIII"• n.AdaJa E. He,,..,,, D, et al: ...... ltlL pp 31We'f.
I.ta: lnaciins. lllpatlcia B 'fine .acciM. AIKI blpo ID llepaticia B -.ccillll ia a ,-ac lldalt IT. Dnm11er J. Colaart J, v, ncraeto Y. et al:
/al.Wff& JI-. tllt91:r.t-ll:I. populaliH. ia Suaa- W. Aliff HJ, Ma,u,d Hepscitil I .--iaatioe ol aunophili&ca. S.:au J
4. Hill•-• MR. McA.i.er WJ. a..,-ul, EB. et JE (edet "'""" H.,,.ali& Plailodelpllia, Fraaldia lw{c Dill UQ:a(111Pfll:424
al: Quality , nd l&l'ety Ill liumaa ltopaciwi 8 IDSUIU\& Preu. 1111. '1145\.._ 11.. s..- W, Sta,..11 EC, ia,. EA, 11 al:
•1cciae. Dr, llilll. Slalli' lta;W:S-lZ. lZ. Holf!IIBM JH. Geroty RJ. Sa&IIWOIIII LA, A -trolled trial ., tkl lfliCIICJ or UII .,patitis
S. Bu,,.11 CJ, lbckay P. c,..u_, PJ, el al: et Ill: S.btffi1111 al ~WI I aarf- u tl..11 I nedllO (Kepcawu: II: A. l-1 npart. Hrpo-
£aprauio11 i• £.cAfflclie coli el llopnciUII B ucu&iW,- •, nd.ioim11111-J. c.u,....,.. ,..,.. l tll;laffl.._
orirut DNA MqUHCft dolllJd in plulnid plltm. ,...,.,,,, lffl;'72:21G-al. lt. rrucia DP, Hadler SC. T1111111paaa SE. tt
J,,.·mrc \t~.ffl:4-41. · 1J. Dliallanlt F, iacllrral I. f,-Of H. IC al: al: n. """"tiea el ti.,&lilil B witb •acc.ine:
, . V&ltaiuel• P, Cray P. Qvirecn lit. el al: Puaifl•a.etift ima■ajutioft apiNt laeptitis I , lepert el IN C..cers tor Dlltuo Contrel multi-
Nuclootide yquaaff of &111 ,.m1 cadiq for tJwr
111a;or pNi.i ■ flf Jwp&tluo I l'lnao e11rfaco uti•
io Enacau S. S-lach S (ak PrwMdiftf13 4/
!All £....,... s.,.,-- ,;i H~i& ~
- I . f f elR-,, trw lmotl8 l,o-JNAI IMI\.
A1111 I ._.. llftl. ltl2;t'T:Jl2·-
--• · .\.eblrc tt'11;2110:SIS-Clt. York, ICPI laleu'Media C«ponliea, l U l. 20. SuiuMl!l W, StlYtu Ct. Harley r.r.
ot al:
'r. Val111auela P, Mediaa >.. Ruttar WJ, el al: ppl~IJO. H.,,.titil I .._.. i11 ae4ical ata6 of htmodia l-
Sr11lhni1 and - •bly of llepoliWI I ffnlll 14. SIIDD- W. Sio,,ooo CE. Hark,y El. et al: ,aia Hits: Efilcacy ucl 111bl1Plf crou-p.. tletiOII.
aurfaee anti,-■ perticlaa i• J9UC, N- \ta; TIMI 1111111... -,.uo 8' lleal~J lldullll le a Ii EJt(lf J Mrd l~:ldl•l"'-
su,-:-.354 l"IIIIIMlll tloae el "°'6&itia B 1'UeiM. I M«J Vire/
a. Hiu.e-11 RA, 0 - CY, ffaaio FE. et al: Jll!l;l:1.ZS-19.
SColnick £~. ~cl~ n M, ~QSt DJ, ~Ale P J. 11hr J, Bu);Mek EG. Clinic l
v 11M1tion in h 1th~ dultz of h !> tith v cc1ne d. .b3,4 r c0ffl!>1n&nt
DA.~ 1 ~. 251:i li-15.
JAMA. Juno 1, 18&4-Vol 251. No 21 Hopo111io B Voccino-Sc:otnick et at 2815
P""'"° ono Put,J;""'1od in "'° Untlod $10101 ol AmoncQ

STUDY 792
00082
PROGRAM: Alu~-Adsorbed Yeast Recombinant Hepatitis B Vaccine,

Study 792
PURPOSE: To evaluate antibody and clinical responses to yeast

recombinant hepatitis B vaccine among health care
personnel who are negative for hepatitis B virus
serologic markers. -
VACCINE: Recombinant Hepatitis B Vaccine

Lot #934/C-)625 (10 mcg HBsAg/ml)
Lot l979/C-K564 (10 mcg HBsAg/ml)
PRINCIPAL Jules L. D1enstag, M.O.

INVESTIGATOR: Associate Professor of Medicine
Gastrointestinal Unit
~assachusetts General Hospital
fruit Street
Boston, MA 02114
SECONDARY Eloise Watkins, R.N., M.P.H.

INVESTIGATOR: Gastrointestinal Unit
Massachusetts General Hospital
Fruit Street
Boston, MA 02114
Lynn F. Butterly, M.O.
Clinical & Research Fellow
Fruit Street
Boston, MA 02114
STUDY LOCATION: Massachusetts General Hospital

Fruit Street
Boston, MA 02114
DATE STUDY INITIATED: November 10, 1983.
DATE STUDY COMPLETED: In progress.
30901/1
12/26/85
000~3
Study 792
STUDY POPULATION: The study population consists of 65 health care

personnel of either sex (excluding pregnant women),
who were negative for HBsAg, anti-HBc and anti-HBs,
had a normal ALT level and had not previously received
any hepatitis B vaccine.
PROCEDURE: Eligible participants receive a 1.0 ml (10 mcg HBsAg)

intramuscular 1njectio~ nf u~rri~A produced by the
inmune affinity or the (b) (4) procedure at 0,
1, and 6 months. Vaccine recipients are asked to
record their temperature da1ly for five days after
each injection of vaccine and also to record any local
or systemic complaints that they may have during this
period.

participant approximately two weeks before the f1 rst
vaccinat\on and on the day of the f1rst vaccination.
Post-vaccination blood samples are obtained monthly
for seven months and at 9, 12, and 24 months from
subjects vaccinated with lot #934/C-J625.
Post-vaccination blood samples are talc.en at 1, 2, 3,
6, 8, 12, and 24 months from persons injected with
vaccine lot #979/C-1(564. The samples are assayed for
HBsAg, anti-HBc, ant1-HBs, yeast antibody and ALT.
Samples with anti-HBs titers ~ 25 mIU/ml are tested
for the proportions of anti-! and anti--s!_ activity.
STUDY RESULTS: HEALTH CARE PERSONNEL (lnmune Affinity Vaccine):
10 mcg lot #934/C-J625 at 0, 1, and 6 months

Injection No.
_L_ _2_ __3_
30 30 27
30901-2
12/26/85
00084
Study 792
RE SUL TS: (Cont. ) 2. Serologic Results:

Serologic data are available for 26 study
participants at 7/8 months. One hundred percent of
the participants seroconverted (S/N ~2.1) and
>10) at that time. The GMT at 7/8 months ldaS
1400.1 mIU/ml (for all vaccinees and for responders
by either cutoff).
Among subjects with serology data at 12 months. 96%

(25/26) were positive for anti-HBs (mIU/ml ~10).
The GMT at that time was 32g.a mlU/ml for all
vaccinees and 436.4 mIU/ml for responders with a
titer ·ot mIU/ml ~10 •.
See Table 1 for anti-HBs responses and GMTs for
other time intervals.
Clinical follow-up data are available for 27
Type of Frequency in% by Injection No.

Complaint 1 2 3
Injection 78(21/27) 43(13/30) 59(16/27)

Site
Systemic 18(5/27) 13(4/30) 11(3/27)

There were no alarming or serious reacttons
ALT Elevations
A 30-year old male subject was noted to have a serum
ALT 3-4 times the upper limit of normal 3 months after
receiving the third injection of vaccine (Lot C-J625).
All sera remained negative for anti-HBt and KBsAg.
30901/3
12/26/85
00085
Study 792
RESULTS: (Cont.) The subject had been taking t~ antimalarial drugs for
tldo months prior to the observed ALT. The reaction
was not felt to be related to the vaccine.
PUBLICATIONS: Dienstag JL, Watkins E, Hinkle C~. Recombinant yeast

hepatitis B vaccine: immunogenicity and safety.
Hepatology 1984; 4:1077 (Abstract).
Oienstag JL, ~atkins E, Hinkle CA. Safety and

immunogenicity of a recombinant hepatitis B
vaccine (Abstract). In: 1/yas GN, Oienstag JL,
Hoofnagle JH, eds. Viral Hepatitis and Liver
Disease. Orlando: Grune and Stratton, 1984:710.
Scolnick EM, McLean AA, West OJ, Oienstag JL,

Watkins E, Deinhardt F. Antibody and clinical
responses among healthy adults to a hepatitis B
vaccine made by recombinant ONA. In: Vyas 6N,
Oienstag JL, Hoofnagle JH, eds. Viral Hepatitis
and Liver Disease. Orlando: Grune and Stratton,
1984:315-17.
30901-4
12/26/85
Table 1
AIITIBOOJ RESPONSES FOLLOl,llNG VACCltlATION MlTH RECOMBINANT HEPATITIS B VACCJIIE
STUOY 0792
POPULATION HEALTff CARE PERSOIIHEl
DOSE t 10 NCG
LOT CJ625
REGIMEN D, 1, AHO 6 t10HTH!I
INI TI AL SEROLOGY: NEGATIVE
I Y. WITH ANTI-HB!I I GHT I HIU/HU I

1---------------------------------------l-----------------------------------------------------
I I I RESPOllOERS
1I
TINE
CtlONTIIS I
1---------------------------------------
I !1/N >= 2.1 I HIU/Nl >: 10
l-----------------
I All VACCINEE!I I
1-----------------------------------
5/H >= 2. 1 I HIU/HL >= 10 I
I
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
I I I
1 HOHTH 40i'. 112/301 6.n: ( 2/301 1. 0 6.6 I 20 . 0
I
2 HONTHS 79Y. (23/29 1 627. 11&/29 1 16 , 7 35.8 I 61.2
3 MOUTHS 93Y. ( 26/2111 757. 12l/21U 29. B 4 J. 0 'II 65 . J
6 MONTHS 96Y. (Z6/Z7 1 857. 125/271 50.5 64.2 I 91 .4

I
718 11011TH!I lOCIY. 126/261 1007. 126126 I 1400 .1 1400. l I 1400 .1
I
9 MOUTHS lOCIY. 124124 I 967. I tJ/24 I '11. 3 911 . J I 1145. 9
I
12 ttotlTHS 961. 125/Z61 967. 125/26' 129. 8 436.4 I 436.4
I
•••••aa•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••~••
0
0
0
a,
0--
Table 2
PATIENT COUNT CUtllCAl COHPLAINTS

R£COMBINANT H£PATITIS 8 VACCINE
SlUOT 07'1l
TR£ATl1£NT
LOT NUt18£R I CJ625
DOSE 10 11CG
PATIENT CLASS: HEALTH CARE PERSOHl«L
I TOTAL VACCJNEES C JO PATIENTSI - DOS£ 1 f

l----------------------------------------------------------------------------1
I OATS POST VACCINATION I tlUMl!ER
1----------------------------------------------------------------------------i
CLINICAL
tQnPLAIHTS I O I 1 • 2
....................................................................
I I
I J
..........
I
• It
.........• I
,
I
5
.......... I
, WITH
.......... ICOHPLAJNTS
I
..........
•
, I
, ,
•
REACTION, LOCAL IINJ£CT. SITEI I 19 • 2 .• " I 1 • t I O • • 21
f C 70.47.1 • C 7 ...7.J I C l't.87.1 • C J.77.J I C 0.07.J I I 0.07.1 I I C 77.87.1
----------------------------------1---------- __________ ,__________ ---------- ---------- ---------- ---------- -----------
SO!tEHESS I lS l I 2 0 II O 16
SS.67.1 C 1.77.1 I I 7.1117.1 I 0.117.t I 0.07.1 I 0.07.1 C 59.JlO
I
TEtlDERHESS I :, l I l O O O "
11.17.1 C ,. T/.1 I C J.77.1 C 0.07.1 C 0.07.1 C a.oz, C 1,.sz1
I
SLOUGH/TISSUE NECROSIS I O O I 1 1 0 0 1
0.0l'-1 C 0.07.1 I I J.17.J C J. 7l'.I C 0.07.I I 0.01.I C J. 77.1
I
HUHBHUS I l 0 I 0 0 O O 1
,. T/.1 c o.or.1 I c 0.01.1 c ,.01.1 c o.o;o c 0.01.1 c s. 77.1
I
PIGftENT CHAN6£ I 0 o I l l 0 I 0 l
I I 0.07.J I O.IU I C J.77.J I ,.no I o.o;o I I 0.0iO I J.77.1
-----------------------------------•----------1----------1----------1----------•----------•----------t----------1-----------
STSTEHJC I O I 1 I l I t I :, I 2 I I 5
I f 0,07.I • c 11.1;0 I I 1.77.J • I 7.4Y.I I I 11.17.1 • I 7.47.1 I I I U.SY.I
&offll! l!!OOY /GENERAL I 0 t 0 a l I l 3

• I 0.0l'.I I 7.41.I ( 0.tY.I I 0.0)(1 I :,.no I J.7)O 11.1)0
FATJGUEINEMtNtSS •I 0 e • 0 1 1 l
0.0l'.J I 0.17.) ( D.D7.1 I e.ox, C 1. 77. J f J. 7l(J ,. 77.1
• •
t!ALAISE I 0 1 0 l 1 t
1.07.) J.T/.t 1.07.1 I t.0l'.I I J.Tr.J J.7)O 7.47.1
H£AUACHE I D
' 1 0 0 0
' 0 l
0.0l'-1 I 1. T/.1 I 0.07.1 I O.tY.I I 0.0Y.J ( 1.0,0 J.T,!1 0
0
0
RESPIRATORY I 0 1 0 l t t t
o.o:o J.T/.J 0.07.1 I J.7:O I 1.4i0 f 7.'t7.1 1 ... Y.I ...,
OD
' '
Table 2 (cont)
PATIENT COUNT CLINICAL Cllffl'LAINTS
REC0tl8IHAHT HEPATITIS 8 VACCINE
STUDY 0792
1Rt:ATMHT
LOT HUHBEA CJ625
IIOSE 10 t1CG
PATUHT CUSS: ttEAlllt CARI PfRsotMl
I TOTAL VACCIIIHS I 30 PUIEHTSI - DOS£ l I

1----------------------------------------------------------------------------
I OAYS POST VACCINATION
I
I tlJ!fflfA
CLINICAL
COf1PlAINTS
l----------------------------------------------------------------------------1
I O I l I Z I :S I ._ I 5 I
MITH
I COHPLAIHTS
a•••••••N••••~•••••••••••••a•e•a••• •••••••••• ••-•••••• •••••••••• •••••••••• •••••••••• ••••••••"•••••••••••••••a••••
RHINITIS 0 0 0 0 l 1 I
0.0Y.I C 0.0iO C o.o:r., C 1.07.1 C :s. 77.1 C ]. 77., C ].7)0
PHARYNGITIS CSORE TffltOAT, 0 1 0 1 l 1 l

0.0lO I J. 77.1
• o.or.1
• J.7XI ( '3.7)0 ( ,. 7?-1
' J.no
H!HIC Atlll LYtlAIATIC o 0 1 1 1 o 1
0.07.1 ( ,.or., I J.T/.1 C J.7:1O I ]. 7?.I I 0.07.1 I J.7)0
lYHJ'tlAOEfCOPATHY, CERVICAL 0 0 1 1 1 0 1
0.0)O 0. 07.1 ,. 77.' ,.1x, I ,.no o.or., I J .7lO
tl\lSCULOSl(El IETAL 0
' 0
' 0
' 1 1
' 0 I 1
,. r1., J.n:,
o.o;o
• O.OlO
• 0.0Y.I I 3. 7?. I I ( 0,07.t I
HYALGIA I o I o I o I l I 1 I O I I l
I I 1 .07.1 I ( 1.07.l I ( 0.07.1 I I ,.no I I J.7?.t I I o.o:o I I I J.T/.J
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEA!IONs ~ITH CottPLAINTS I 19 I s I g I J I , I z I I 22
I c 10 ... r., I t H.s;o I c u.sY.1 I c 11.1;,:1 I 1 11.1x1 I c 1 ...1.1 I I , e1.s;o
-----------------------------------1I----------
PERSOHS MITH NO tOHPt.Aoos e I
I----------I----------I----------I----------I----------I----------I-----------
22 I 22 I 2, I t~ I zs I I s
I c n.,r.1 I c 81.si, I c 81.57.1 I c ea.,r.1 I I ea.,1.1 I c 92.67.J I I c 18.sr.1
-----------------------------------1I ----------I----------I----------I----------I----------
PERSONS ~ITK Nt> DATA J I 3 I 3 I J I 3
I----------I----------I-----------
I J I I J
I C 10.0Y.I I c 11.0::0 I c 10.0:0 I c Ja.0Y.J I I 10.or.1 I I I0.tl(J I I c 10.or.1
0
0
0
OD
0,
Table 2 (cont)
PATIENT COUffT CLI NICAL COHPlA INTS

RECot18ItlANT HEPATITIS B VACCUIE
STlRJY I 17'1Z
TREAfflE NT
LOT NUltBER C.1625
DOSE 10 tlCG
PATIENT CLASS HEALTH CARE PEll!lemffEL
I TOTAL VACCIHEES C JO PATIENTS, - DOSE Z I

•----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUtlBER
CLINI CAL
tonPLAlNTS
l----------------------------------------------------------------------------1
I t . l I 2 I J I 4 I 5 I
MITH
ICONPLAI NTS
a••••••••••••••••••••..••• .. ••..•••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••••••~••••a
I • • I I I I I
IIEACTION , LOCAL I I NJECT. S ITE I I lZ I 1 • 0 • 0 I 0 • 0 I I lJ
I , 4o.o;o I , J.J:r.1 I 1 , .o;o • , o.oio I I o.o;o I 1 0 . 0¼1 I I , u. 1:0
-----------------------------------1----------1----------1
!0REHESS ' I JO I l I ----------•----------1----------1----------1----------•-----------
O I O • 0 I .0 I I 11
I l J J. J iO I I J.37.J I I O.OiO I ( o.o:o I ( o.or., , . , a.or., I I I J6.7U
I I I I I I I I
111M>ERHEss I z I o • o I • I · o I a I I 2
I c 6.11.1 I 1 , .or. , t , e.07. 1 I , o .1Y.1 I c o.or., I , o.a:o I I c 6.77.J
-----------------------------------1----------1----------1
STSTEHIC I 0 I 0 I
----------1----------
1 I 1
1I ----------1
Z I
----------1----------
1 I
1I -----------
4
I I o.o:o I 1 1 .or. 1 I c J. 37. J I , 1.1:0 I c , . 1r., I c J.JY.I I I I n.J7.I
------------------------------------1
&OtOLE BCUYIGEHERAL I 0 0 I 1 1 0 l I J
I ( t .0lO I 0.07.1 I I J ,JlO I J.J,O I 0 .17. t I :!I .Jr.) I I lD.0Y.I
I I I
FATIGUEINEAKHES!I I O O l O t O I l
I I 0.0iO I t .07.1 I J. 3XI C O. t 7. t C o.or., I 0 .0X I I ( J.37. 1
I I
t1A LAISE I O O O O I 1 I l
I , o.o:o I o .o:o , o .or.1 c o .or. , c o.,r., 1 J.Jr. 1 1 3 .37. 1
r
HEADACHE I 0 O 0 l 0 0 l
I I 0 .0Y.I I o .oxt I o .or., I J.JiO I 0.07.1 I 0.0iO l J.37.1
RESPI RATaitT •I O O O O 2 1 Z
I 1 , .o:o , o.or.1 , o.or. 1 1 o.o,o 1 ,.1r., I I J .1x 1 1 6.77.1
I I
fHARTHGITlS I SORE llfllOAT I I 0 O 0 O l I I 1
I I I .OY.I I 0 .OlO I 0. 0lO I 0.0Y.I C J.37.1 I C 0 .07.1 I J .37.t
I I
UPPER RESPIRATORY I M' fCT., NUS I O l O O O l I l t
Q
It O.OY.I I t O.OY.I I O.GlO I o.o:o t l.37.1 IC l, 17. 1 I I 6.7%1 0
-----------------------------------1----------t----------
O'fR!ION! NITN COHPLAJNT!I I 12 I 1
l----------
• l
l----------l----------l----------l----------l-----------
I 1 I Z• I 1 I I H
0
~
I I , o .0Y.I I I 3.J7.I I I J.JY.I I I 3.37. 1 IC 6.77.t I I J .Jr. t I I I 46.7Y. I
'°
Table 2 (cont}
PATI ENT COUNT ClIHICAL Cot1PLAIHTS
R(COt1BmAHT HEPATITIS B VACCINE
STUOl' 0792
TRUTl1EHT
l OT NUHM'R CJ6Z5
005( 10 t1C&
PATIENT CLASS HEALTH CARE PlR'OHNEL
I TOTAL VACCIHft:S I 30 PATIENTSJ - DOSE t I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I ~ ER
Cl l HICAl
COl'IPLA IHTS
l----------------------------------------------------------------------------1
I O I I • Z I l • 4 • 5 •
WI TH
ICONPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••1•••••••••••••••••••••1••••••••••1••••••••••1••••••••••
-----------------------------------1----------
PHSotlS 14I nt HO COt1?lAINTS I 18 l----------•----------
I H • H
I----------
I 29
I----------
• :!II
I----------I----------I-----------
I 29 I I 16
I 1 60.0;0 I 1 96.77. 1 I I 96.7,n I I 96.7iO I I 95 . 37.I I I 96 . 7iO I I I 5 3 .37. 1
-----------------------------------1
Pt:RSOHS IUnt NO DATA I ----------
Cl
l----------•----------l----------
I ct I O I O
•----------t----------
• 0 I O
l----------1-----------
I I ct
I I 0.07. 1 I I 1 .07.1 I ( O.OZI I I O.OZI I I O,OZ I I t O.DZI I I I O.DZ I
0
C
0
-0
0
Table 2 (cont)
PATIENT COIJKT tllHJCAl tot1PlAIN19
RfC0'181HAHT HEPATITIS 8 VACCINE
STUOY 0792
TREATt1£HT I
LOT tlUt!BfR CJ625
DOSE 10 11'C&
PATIENT CtAss: HEALTH CME l'tRSONNtl
----------------------------------------------------------------------------------------------------------------------------
I TOTAl VACCIN£ES I 27 PATIENTSI - DOSE J I
1----------------------------------------------------------------------------I
I DAYS POST VACCINATilltl I NIRIBER
CLJNJCAL
Cot1PlAIHTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I J I 4 • 5 I ~JTH
ICONPlAIHTS
qaaaaaaa•a•a•a•••••••••tt111•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••aaaaan
. I I . I I I • I I
Rl!:ACTIOH, totAt IIHJECT, SITEI I 14 • 5 • 5 • 1 I 2 • 1 I I 16
I t 51.91.I I ( 18.51.1 I I la.SY.I • , 1.1:1.1 I t 7.41.1 I c 1.11.1 I I t s•.1;:1
-----------------------------------1----------1---------- ---------- ----------1---------- ---------- __________ ,__________ _
PAIN • 1 I O O 9 I O O I l
I J. 71.1 I l· 0. 01.1 I O. 01. I t 0. e:o I t 0. 01. I I I. Oi! I I t l. 7X I
SOl!EHESS I 12 I• s s 1 II 1 1
•
I n
44.4i0 I I 18.5)(1 l la.SY.I I J. 1r.1 I t J.7i!l I 3.7i0 I I 48.17.1
I I I
TEIIDERHESS I l I O D D 1 D O I 1
J.77.1 • l 0.0ln ( 0.01.I I 0.0Y.I \ I 0.o:O I 0.010 1I 3. 7:0
I I I
SM£LUNG I O I O · 0 0 I I O I I
I O.D7.t • I 0.07.1 I 0.01.1 t 0.07.1 I I 3. 7l!I t o.o:o I I J. 7?.I
I I I
PAPULUSI I l I l 1 1 I I l I 1
• l J.77.t ( t J.77.1 t J.71.1 t J.7l0 I I J.Tl.l I 3.7:t.l I ( J.77.1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
srsn111c I D I l I o • 1 I o • o I I :s
I I o.o:o I t u.uo I I 1.1?.1 I I J.11.1 I t o.o;i1 I t t.07.1 I I I ·11.17.1
----------------------------------------------------------------------------------------------------------------------------
I
laiOLE IIIOOYl'G£H£RAl I 0
o. 07. J I
t
7 .47.J I •
0,07.1
1
J. T/.1
0
0.07.1 I
0
D.0lJ
t
I I
2
7.47.1
'
(
I
SEHSATIDH M IIIAlttfflt. OtHEltAl I 0
0,07.1
l
J, T/.J I •
0.DiO
0
0.0lO
0
o.o:o (
0
11.07.J
I
I I
l
3. 77.1
'
( C
I
HEADACHE I 0 I 0 1 0 0 I l
I o.o;o J. 77.1 0.07.) J.71.) 0.07.I o.o:o I
' C I
' I
I
I 3.T/.1
R!SPJltATOIIY I D
0.07.J
l
J.7,)0
D
0,DlO •
0.07.1
0
o.o:o
D
o.o:o
I
Ic
1 0
' C I 3.7::0
C C ( 0
I 0
UPPER RESPl!RATO!tY Jtlf'ECT., HOS I 0
D.07.)
'
1
J.T/.1 (
D
D.07. I
'
•
D.liO C
0
o.o;o
'
0
a.o::o
I
I I
1
· J.7i0 -
.0
Table 2 (cot;1t)
PATIENT coum ClIHICAl COHPLAINTS
RECOtllIHANT HEPATITIS 8 VACCIH£
SnJDY 0792
TREATt1ENT
lOT tlUMBER CJ62S
DOSE 10 MCG
PATIEHT CLASS HEALTH CARE f'tRsm&IEl

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I Mllt16Elt
CUHJCAL
COMPUIHTS
1----------------------------------------------------------------------------•
I e I -1 • Z I J • t, I 5 •
WITH
•c0!1PLAINT9
••••••••••••••••••••••••••u••••••••••••••••••••••••••••••••••••••••••••••••••• ••••••••••••••••••••••l••••••••••I••••••••••
-----------------------------------•----------l----------l----------l----------1----------1----------1----------I-----------
PERsONS MITH conPUINTS I I to • e I s I 2 I 2 I 1 • I 11
• ( 51.91.1 I ( t'J.6i0 I I 1e.s;o • ( 7.lt1. I I ( 7.lt1.I • C ]. 71. 1 I 8 I 63.o:o
-----------------------------------1----------
Pt:RsOHS 141TH NO conPLAINTS I n
l----------l----------t----------l----------
I 19 I u I 2s I 2s
l----------l----------
I u I
l-----------
I 10
I C fi8.UO I C 70.ti1.I I l 81.51.1 I f 412.61.1 I C ,2 .67. I I C '96.Jr.t I ! I 37.01.t
-----------------------------------•----------1----------•----------1----------1----------•----------1----------1~----------
PEIISON5 MnH HD oAn I o I II I o I o I o I o I I o
I C O.OlO I I I .Oi'.I • I o.Oi'.I I C o.o;o I I 0.07. 1 I I o.o:o I • I o. o:o
0
0
~
-0
rv
Table 3
PATIENT COUNT " AXI.-m TENP£RATURES
AECOt1BINANT HEPAT I TIS B VACCINE
STUDT '792
TREA1l1ENT
LOT NU118EA CJ6t5
DOSE 10 tlCG
PATIENT CLASS HEALTH CARE P£RD&fEL
• TOTAL VACCINEES I JO PATIENTSI - DOSE 1 I

•---------------------------------------------------------------------------------------1
• DAY S POST VACCINATION I tM18ER
HAK TENPERATUIE
(0£6 f, CJRAl I
l---------------------------------------------------------------------------------------1
I I • l I t I l I It I 5 • I
MITH
I t1AK TENP
ttu•a••••••••••••••••••••••••••..•••••••••••••••••..•••••••••••••••••• ..•••••••••..•••••••••..•••••••• l••••••••••I••••••••••
I • I • I I I •
< 99 I ts I t5 I 25 I n I 22 I 25 I • 17
I ( 83.]7. I I I 86,t,(I I I H ,J7.I I ( 85 ,ZlO I I 78 .6% 1 f I f
8 9.]i! I I ( 56.71.1
I I I I I I I I
99 - 99 .9 I !I I 1t I s I ,. I 6 I J I I n
I ( 16.77. 1 I I 13,ein I I 16.77. 1 I I 14 .8l0 • ( U .ltll. l I I 10.7:iO I I I O .Ji! I
------------------------ l----------l----------l----------
tElff'ERATURE TAKEN I 30 I 29 I 30
l----------
I 27
t----------l----------1---------------------1--..
I 28 I 28 I I
--------
30
I U OO.OY.t I I 96.7Y. I I 1100.0lO • I 90.0)0 I ( 93 .]i!> I ( 9].]lO I I U 00.07. 1
------------------------ l----------l----------l----------
TEHPERATURE NOT TN<EN • I I 1 I O
l----------
• J
•----------1----------1---------------------I-----------
I 2 I t I I O
I I o. 07. 1 I c 3 . 37. I I t o. 07. I I I 10. o,o I l 6. 7U I I 6 . 7:iO I I I o. 01. I
0
~
0
-0
i.,,
Table 3 (cont)
PATI ENT COUNT nAXtHUtt TEHPEAATUl!ES
RECoteINANT HEPATITIS 8 VACCINE
STUDY 0792
TRUTHENT
lOT IM1BEA CJ62S
005! 10 HCG
PATI ENT ClASS HE Al l N CARE l'tRso»f!l
• TOTAL Vl'CCINUS I JD PATIENTS I - 005£ 2 I

l---------------------------------------------------------------------------------------
• DAYS POST VACCI NATION
1I HUHBl!A
M X TEMPERATURE
I DEG F , ORAL I
l---------------------------------------------------------------------------------------1
I O I 1 I 2 I J I - • !J I •
MI TH
• HA)( TEMP
a••••••••••••••••••••••••••••••••••l•••••••••••••••••••.. •••••••••••••••••••••••••••••••••1••••• ••••1••••••••••1••••••••••
5
I I I I • I I I
< 99 I 2S • 25 I 29 • H I 25 I 2S I I 20
• c u. 11. 1 I c 83 .31.1 I I n.s;o • 1 86.2:0 I c u.1io I 1 86 . 2:0 I • c 66 . no
I • I • • I I I
" - 99. 9 I s I s I z I 4 I s • 4 I I 10
• t 16. Tl.I • t 16. 71.1 I I 6. Tl. ) • I 13 .IIU I I 16 . T/.I I I 13.lllO t I C JJ .11.1
------------------------•----------l----------l----------•---------
TErtPfRATUlfE TAKEN • 10 I JD I JO I n
•----------l----------1---------------------1
I 10 • u I I
-----------
n
I U 00.01.1 I nee.or., I IUD.DY. ) I I 96.7l0 I U00 . 0)0 I C 96.7)0 I I uoo .o:o
------------------------•----------•----------1----------1
TEl'IPtRAttmE HOT TAKEN I I I a I 0 •
---------1----------•----------1---------------------
I I D I l I
•-----------
I o
I c 1 . 11. t I c 0 .01.1 I I o.or. J I c 3.17. J I I 0.01.1 I c J . J:f.l I I c o.o;o
0
0
0
'°
~
Table 3 (cont)
PATI ENT COUHT HAXlfflJH TEttPERATlllES

RECOHBINANT HEPATITIS 8 VACCINE
STUDT Ont
TRU THENT
LOT HIR181':R I CJ625
DOSE I 10 t1CG
PATIENT CLASSI HEALTH CARE PERSOMtEL
----------------------------------------------------------------------
• ·-----------------------------------------------------
TOTAL VACCINE.ES f t7 PA TIEHTS t - OOSE 3 I
. 1f ---------------------------------------------------------------------------------------I
DAYS POST VACCINATION • MJNIIER
NAX TENPfRAT\JRE 1 --------------· ------------------------------------------------------------------------1 WITH
l DtGF,ORAU
·-·················
< 99 I•
It
u
.. ••
•
21
l
II
•
21
2
I•
• I 81.51. 1 • I IID.8l0
I
19
J
••
I I
•
20
M.llO
"
I•
I I
20
•
•I
S • •
76.0?.I • I 8 0. 1?. >

II
I I
IHAXTEHP
·············•···········································•·····················•·····················
15
8 0.0,0 • I C 55 .6?. t
I • • • • I
99 - 99. 9 • s I s I " • 6 I s I s I• I
I 12
• I 18 . !5%J • f 19.21. J • C 1 ♦ .0lO • I t4 . D1.I • f tD. 01.1 • f to.01.) I I I ...... lt?. I
------------------------1----------
TEHPERAT\mE TAKEN • 17 I•----------1----------•----------•----------•----------1---------------------•-----------
26 I 25 • 25 • 2!5 I 2!5 • I 27
I noo.ox, I ( 96.J?. ) I f 92. 6?. f • ( ,t.61.l I I '2 . 6i0 • f U.6)0 I I H00.0)0
------------------------
TENPfllAl\JSIE HOT TAKEN •----------
• 0 I•----------l----------•----------
1 • 2 • 2 I•----------•----------1---------------------
2 • 2 I •-----------
• O
I C O.OlO I C J.n , I I 7 ...)( f • f 7. 41.) I I 7 . ..)0 • f 7.lt:o • • I O.DlO
0
C
::>
,0
IA
OOOQ6
lltCOKBlM.U.,- Y'tA.ST K!PATITlS I VAO:lNt: 1MHt.'IIOC0l1ClT'r Al\"i)

SATt'TT. J1. Dhntitu 1 £ \;atlt1n I a11d CA lll111th • .
~-•tTotlllCGl1D&\ Uu1t, ~.,oachu•ctts ~CDCT&l io,,\tal,
loateCl, >IA.
Cftlkrl- to p,o4vco·, oiq>ena1.'<e. ad limha4 111
eupply, curTe11cly av1!lable hUCW1n ploa1l41-det1vo4 h•~•tlcia
a •acc1nat ere 111tely te ~ replaced Sa cha fwturc by
•1•n•tlcall7 1n11nee,ed~ •accbaa. l&ccntly, a
recoaDlA&nc D~A •ecc1Da vaa prcpered la recwDLMllt 7•••c
S&cch•r_.,c•• car••1•1•• ■ train ll,0..2•l calls tranafonwi4
vtth chc plaaald pHIS S~.IJ'l47/3!, coat&1A1al the gCM
for h ■ pacicu l_eurface ancigea (WlcAs/!!l (Valca.cuai. cc
al. lllt11ta 1181; 2U:l'7•SO). hri!hd l,y \iochdiul U<i
b1ophya1cal tho41 ft the ycacc cscract, the DaAg
particle• 1711che1i1c4 by the•• 7•••t cell ■ arc••« ·
glycoaylaced but echctvi ■ e arc ia41ac1ag,,1ahcble frKJ
aativc 22 Kia.Ag particles. treated rich fel'IMl11a au!
ad,otbo4 to •1-, tho rac-•l~ont •acci•• 1• i-01••1c
•a• ,recactS•• la •aJMr1.INatal u1&al1 • . ~• ataiaiacctod
three 10 u; doacs of chc tccoabiaanc be,ettti• J .•• ccillo
(Merck Sharp, 1>c,harc le,earch ~'aoracorice) ,c tis,a 0, 1.
atwl I a oacha to 60 1croao1ac1•• adulc health vorkers. The
h.•~--•c, 11141 1• cuic Mall tUu (slV/•ll •f a11t1.-Us
re•-••• voro •• foll-•:
llontll 1 2 l 4 ~ 6
Jhmbcr 37 2, 30 2! ·25 16
encl-II •• 411 • &lt 931 '71 9'1 ,,1
CMT: St> 7: 1 33: S 36: l ,, : , ~5: 6 ,, : 4
,4: 1 { 1H1aa : . ~ ) i of tho ent1•¥11 va• apcc1C1t for the •
.!. ••ccni1unc •f Kl,Ag. Ole•s•• ia e:1t111oc!1ct t• yca,c
uc1c•aa vcre acgl1giblc. The aoat frequut adverse
reacti•• vaa tr-81ent eorcn••• ac the Ss1Ject111l •1to.
Kcurru.n after S21 •f f1rat, 311 oC ••c0114, &M SSl of
third laJcctiOIUJ. No ••~iou e ad••r•• cf!act, were
cncouat,rcd, a"41 aclthcr t)'1MI I nor aoo-9 bcpec1tia uu
occurred 111 aay vacciaoc. The•• preli&iaa~ 1a111lta
d-a,ctata that the rec-blll4at 7aa•t be114t1tia I Yacc1na
1• aa[e and tbat 10 UI a{ the rec•11Ml11t ••cc1 11
equ1•a1c11t 1a SB=Nnoaea1c1cy to 20 ug of tbcl
platn:14-4er1••• •ecct..e.
\
01QnSt8~ ll tk1ns E, M1nk1G CA. fi c 1rwnt YQ~$t h i~i1t1$ 8 ~icc1ne:
0
1 nos,Qn1c1ty n~ $ f ty. M@§tolom, 1~84; 4:1077 (Abstr ct).

ooocn
SAT-LA.SO .
SAFETY AND lMMUNOOENlcrrY OF A llECOMBlNANT HEPATITIS B VACCINE
J.L Die,.tag• , E. Watlclns, Md C. A. Hlnkkt
Gutrolnteetwii Unit (Medlc61 Serrietil), Pllusac:hulett.s General Hoapitcl, 1111d Department ar
Medleinc, H&l'Vatd Med.led School, ~ton., MUKchc»etts 02114
Currently available, licensed heptilltls B vaeelnes are pl'epued fro,a plasma obtained Crom hepatitis a
llurface antigen (HBIIAI) carriers. Cumbenome to produee, ezpenslve, a nd available In limited supply,
the pleS ma vaccine ii likely to be r.pl&ced In tM future by one of a number of later reneration vaccines.
Recently, 11 recombinant DNA vaccine "'u prepared In recombinant yeast S.cchyomyces cerevisiae
s tra in 2150-2-3 cells u-11t111Cormed with plasmid pHBSH-GAP347/33, which contains the rene tor H&Ar
(Valensuela et al, Nature 1912; 218:3 41•~0). The HBIAC synthesized by these yea.st cells wu purified
from tM yeut ntraet by physical and chemlc:Bl methods and wu found to be lndistincuistlable rrom
na tive 22 n111 HBsA.(r partJclu , except tllat th HBsAr II! not r tycosyla ted. Traated with formalin and
a dsorbed to alum, the recombinant vaccine Im eompunble ln P'lf'lty to th4I pluma vaccine ancs Is
lmmurqenfe and protectlH In experimental animals.
We studied the lmmunoreniclty and safe ty of tecombtnant hep&tltls B vaccine Lot 93.C, formulate~ to
contain 10 microgra ms or HBsAr per 1.0 ml dole (~ erdc Sharp 6: Dohme Research Laboratories). Thirty
seronerative adult health C8te workers recelved three 1.0 ml doses or the recombinant vaccine at time o,
1 and 6 months. Adverse ecrec:ts were limited to soreness &l tl\e lnje<:tkm site, and lmmunorenicity "IS
excellent, appl'C!ICimating 509' t one month. 'nlreci months or follow-up wW be complet e by tl\e time oC
the International Mffll"(, ·
01,nsteg Jl, tk1n1 E, H1nkl CA. Sifety end 1 nogen1c1ty of a recombinant

hepat1th D v&icc1n (Abstr1ct). In : Vyu &CJ, Oienstav Jl. Hoofnagle JH,
Clls. V1r 1 Wp t1t1s nd Liv r 01s as . Orl n~o :_6r'ln nd Stratton,
lH<l:710.
OOOQ8
Edward M. Scolnick, Arlene A. McLean.

David J. West, Jules L. Dienstag.
Eloise Watkins, Friedrich Deinhardt and Wolfgang Jilg
23
Antibody 11nd Clinical Responses Among Healthy
Adults to 11 Hepatitis B Vaccine Made by
Recombinant DNA
Currently, all commercial hepatitis B vaccines are comprised of HBsAg purified

from the plasma of human c:anien of the virus. However, the use of recombinant
DNA technology to effect synthesis of surface anti1en by a culture or microorpn-
isms is an attractive alternative to infected human plasma as a source of HBsAg
for vaccine. Good expression of the acne for HBsAg has been effected in yeast
(I}.
Recenlly, antigen purified from fermentation cultures of a recombinant strain
of the yeast, Saccharomycts certvisiat containing the 1ene for the adw.• subtype
of HBsA1 was formula1ed into a vaccine throu&h absorption on alum adjuvant.
Two melhods wert utilized for the purification of the HBsAa. Immune affinity
c:hromatography uses specific anti,en-antibody binding to effect purification, while
the second method, hydrophobic interaction chromatopaphy followed by gel
exclusion chromatop-aphy, depends upon the selection of water-immiscible mol-
ecules followed by separation on the basis of molecular size.
The physical and chemical characteristics of vaccine made from HBsA1 pro-
duced in yeast are very similar to those of vaccine prepared with HBsAg purified
from hurMn plaslu. Funt,crmore, the yeast recombinant hepatitis B vaccine has
been shown to be both immunosenic and protective in animals (2).
We repon here the clinical and antibody responses obtained in the firs1 three
human clinical studies of the yeast recombinant vaccine involvina a 101&1 of 101
VIRAL HEPA T1T1S and LNEA 0CS£ASE Coclyright e 1 by GIVM It StnlftOI\

ISBN G40&9-187&-5 All rights of rwp,oOUClion In '"" form ~ -
scolnic E~. ikL n • st DJ, 01 nst ~ JL, tkins E, O 1nh rdt F.

Ant1bodr nd cl1n1c&1 n!spons s Heh ~1th~ dults tc ~ hep~titis B
v cc1n d~ by MIC 1n nt D~A. In: Vy i , D~ ft$t ~ JL, Hoofn~gl JH,
ds. '11r 1 w p tith l!nd Liv r Oh io. Orl nc9o:6rune nd Strctton, 1984:
31$- 17.
316 Scolnick. McLean, West. at al
vaccinees. Participants were healthy, nonpregnant, adult volunteers. At entry,

subjects were neptive for all hepatitis B serolc,eic markers, had a normal ALT
level, and had not received any olher hepatitis B vaccine.
Participants in the studies received a 1.0-ml intramuscular injection or the
yeast recombinant hepatitis vaccine containing 10 loLI! of HBsAc at O. I and 6
months. The vaccine used was from one of two lots. (Lot 934 prepared by the
immune affinity chromato,raphy method and Lot 972 prepared by the hydrophobic
interaction chromatopphy mechod.) Vaccinees were asked to record their tem-
perature daily for 5 days after each iruection of vaccine and to report any local or
systemic reactions thllt °"uned during that period.
B serologic markers and ALT. ln addition, a radioimmunoassay for lhc detection
of antibody to antisens in an· extract of yeast lacking the pne for HBsAg wu
applied to pre- and postvaccination samples.
The vaccine was weU tole12ted. There have been no serious adverse eff'ect,
a ttn"butable to vaccine and no evidence of hepatitis B infection among the vaccinees
(i.e., no elevation of ALT and no antigenemia). Loc:al reactions consisting prin-
cipally of mild soreness at the iqjection site, senerally lastiq 1-2 days, have been
reported foUowing 209E-80% of iqjections with vaccine purified by the immune
affinity chromato,nphy method (Lot 934) and I69'-25% of injections with vaccine
purified by the hydrophobic interaction chromatography method. Systemic com-
plaints including fati1ue, headache, elevated temperature (1019 F-102" F, oral),
pstrointestinaJ disturbance, symptoms of upper respiratory infection and nose-
bleed have been reponed followin& 4%-339li of iqjcctions (Table 23. 1). There have
been no significa nt increases in antibody to antiaens in yeast extract ~nociated
with vaccination.
Table 23.1
Oinic:al JlesPonses among Healthy Adults to JO 16& Doses or
Recombinant Hepatitis B Vaccine Administered al 0, I and 6
Months
Proponion (Iii) of Vaccinecs with Clinical Complaints
within .5 Days of Vaccination
Study tJ Vaccine Lot ii Site Dose I (9') Dose l (~l Dose3 (~)
m 934 Local 12/15 (IO) I 1/1.5 (73) 11/1.5 (73)
Systemic .5/U (33) 3/U (20) 1/1.S (7)
'97l Loc:al fJ24 (25) 3119 (16)
Systemic 1/24 (4) 3119 (16)
792 934 Local 19/ll (68) . 11/21 (39)
Systemic '12108) 4".J (1 4 )
79S 934 l...ocaJ .5125 (20) 6,'19 (32)
Systemic .5125 (20) 1/19 (5)
00100
HSV V11ccinE MIXfc;i by Recombinant ONA 317
Tebla 23.l
Scroconvenion Frequencies for Anti-HBs among Healthy Adults
Receiving 10 Jl-8 Doses of Recombinant Hepatitis B Vaccine 111 0, I
and6Months
Proportion (9') of Vac:cinees with Antibody
Study 1/1 Vaccine Lot C !Mo. 2Mo. JMo. 6Mo. 7Mo.
779 934 &115 14115 l.~/15 1,,1, 14/14
(40) (93) (100) (100) (100)
m 1/24 ISl\9 12/14
(29) (61) (86)
792 93' 11/21 21/23 ll/13
(39) (91) (100)
934 &/30 21/30 19122
(27) (70) (86)
Antibody responses to JO l'8 doses of

the yeast recombinan1 vaccine have
been comparable 10 those observed in previous studies with 20 ~ doses or vaccine
prepared from plasma-derived HBsAg. At I month, 2 7 ~ or the vaccinces
were positive for anti-HBs. By 2 months, 68~93CJi of' the vaccinees had anti•
HBs, Md at 3 months 86~1009' were anu"bocfy. positive (Table 23.2). The third
dose of vaccine at 6 months has been given to l~ persons in one of the studies.
resultin1 in a more than 25-fold increase in geometric mean titer.
REFERENCES
I. Valenzuebl P. Medinll A. Rutter WJ, cul. Synthesis and assembly or hepatitis B virus
surfi cc antigen panicles in yeasL Nature 1912: 291:347-350.
2. McAJcer WJ, Buynak EB, Mai,ener RZ. et al. HWlllft hepatitis B vaccine from
recombinut ycug. Nanire 1914: 307:171-IIO.
00101
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepat1t1s B Vaccine,

Study 795

recombinant hepatitis B vaccine by health care
personnel and other healthy adults negative for
hepatitis B serolog1c markers.
VACCIHE: Yeast Recombinant Hepatitis B Vaccine

Lot #934/C-J625 (lOmcg HBsAg/ml)
Lot #979/C-K564 (lOmcg HBsAg/ml)
Lot #81990 D/18066/C-L215 (10 mcg HBsAg/0.5 ml)
PRINCIPAL Prof. Dr. Friedrich Deinhardt

INVESTIGATOR: Max v. Pettenkofer Institut
Pettenkoferstrasse 9a
8000 Muenchen 2
WEST GERMANY
SECONDARY Or. W. Jilg

INVESTIGATORS: Dr. R. Zachova 1
Dr. G. Zoulek
Or. 1'1. Kroner
Or. J. Abb
or. 8. Lorbeer
The above secondary investigators have the same

address as the principal investigator.
Dr. u. Bienzle
Landesinst1tut fuer Tropenmedizin
Ansbacherstr. 5
0-1000 Berl in 30
WEST GERMANY
STUDY LOCATIONS: Max V. Pettenkofer Institut

8000 Muenchen 9a
WEST GERMANY
Landesinstitut fuer Tropenmedizin
Ansbacherstr. 5
D-1000 Berlin 30
WEST GERfl!ANY
25411-1
12/31 /85
00102
Study 795
DATE INITIATED: November 21, 1983.
DATE COMPLETED: In progress.
STUDY POPULATION: The study population consists of approximately 300

health care personnel and other healthy adults of
either sex (excluding pregnant women), who are
negative for HBsAg. anti-HBc and ant1-HBs, have a
nonna l Al T level and have not previously received any
hepatitis B vacc1ne.
PROCEDURE: Eligible participants receive a 10 mcg tnjectton

intramuscular injection of vaccine produced by the
innune affinity or (b (4) procedure at 0, 1,
and 6 months. vaccine recipients are asked to record
their temperature daily for ftve days after each
injection of vaccine and also to record any local or
systemic complaints that they may have during this
period.

participant approximately two weeks before the first
vaccination and on the day of the first vaccination.
for seven months and at 9. 12, and 24 months from
recipients of lot #934/C-J625 vaccine. Rec1p1ents of
lots #979/C-K564 and #8199OD/18066/C-L215 are bled at
1. 2, 3, 6, 8, 12. and 24 months. The samples are
assayed for HBsAg, anti-HBc, anti-HBs, and ALT.
Samples with anti-HBs titers ~ 25 mIU/ml are teste4
for the proportions of anti-! and anti-g_ activity.
Samples may also be assayed for yeast antibody.
25411-2
12/3 l /85
OOlOl
Study 795
RESULTS: HEALTH CARE PERSONNEL (lmnune Affinity Vaccine):

10 mcg Lot #934/C-J625 at 0, l, and 6 months
Injection No.
_1_ _.1_ _3_
30 30 30
2. Serologic Results:
Serologic data are available· for 29 participants
subjects seroconverted (S/N ~2.1) and developed
protective levels of ant1-H8s (mlU/ml ~10) at that
time. The GMT at 7/8 months was 1735. 7 mIU/ml
(all vacc1nees and responders by either cutoff).
Among participants with serology data available at
12 months, 93% (25/27) were positive for anti-HBs
(mIU/ml ~10). The 6"T for all vacc1nees at that
time was 271.5 11IU/ml, while it was 419.2 mlU/ml
for subjects with titers of mIU/ml ~10.
Refer to Tab le 1 for ant 1-HBs responses and GMTs
Clinical follow-up data are available for at least
23 participants after each injection. The overall
frequencies of c0111plaints are presented below:
Type of Frequency in % by Injection No.

COIIJ!la1nt 1 2 3
Injection 21(6/29) 28(7/25) 26(6/23)

Site
Systemic 21(6/29) 8(2/25) 9(2/23)
25411/3
12/31 /85
00104
Study 795
RESULTS (CONT . ): Refer to Table 2 for listings of specific

compla1nts after each injection. Maximum
temperature data are presented in Table 3.

PUBLICATIONS: Deinhardt F. Jilg W, Zoulek G, Lorbeer B. ~ilske B.

Clinical evaluation of a recombinant hepatitis 8
vaccine. In: Vyas GN, Oienstag JL, Hoofnagle JH,
eds. Viral Hepatitis and liver Disease .
Orlando: Grune and Stratton, 1984:699.
Jilg W, Schmidt M, Zoulek G, Lorbeer B, Wilske B,

Oienhardt F. Clinical evaluation of a recombinant
hepatitis B vaccine. Lancet 1984; 2:1174-5.
Scolnick EM, Mclean AA, West OJ, Dienstag JL,

Watkins£, Oienhardt F. Antibody and clinical
responses among healthy adults to a hepatitis B
vaccine made by recombinant DNA. In: Vyas GN,
Dienstag JL, Hoofnagle JH, eds. Viral Hepatitis
and Liver Disease. Orlando: Grune and Stratton,
1984 :315-17.
25411-4
12/31 /85
Table l
AHTIBOOT RESPONSES FOLLOWING VACCINATION WITH 11£cot181HAHT HEPATITIS 8 VACCIH£
ST\JDT 0795
POP\JLATIOH HEAlTII CARE PlRSOHHEL
ODS£ l 10 HCG
LDT CJ625
REGI HEH 0, 1, AHO 6 HOHTHS
I Y. WITH AHTI-HBS I GttT IHIU/Hl) I

l---------------------------------------l-----------------------------------------------------1
I I I RESPOIIDUIS I
1Il1E
1110NlffS I
l---------------------------------------l-----------------1-----------------------------------I
I SIN >= t.l I HIU/Hl >= 10 I All VACCINEES I SIN>: 2 . 1 I 11IU/11L >• 10 I
••••••••••••••••••a••••••••••••••••••••••••••••••••••••••••••••••••••••••~••••••••••••••••••••••••••••••••~••••••••
I I
1 tlOHTH 28Y. (&/t9 ) I 1or. U/Z91 I o.a 11.6 25.D
I I
t NOHTIIS 127. Ul/:t91 I 591. tl7/291 I 10.11 37 . 5 55.7
I I
J ttOIITHS 96Y. (27/211 1 I 71 7. 120/2111 I 22 . 11 26 .& _ 50 . 5
I I
6 tlOHTHS 97Y. (2&/291 I 1161. 125/291 I 4& .S 511 . 2 75.7
I I
7/8 tlOtlTHS lllOY. 129/29 1 I 1007. 129/291 I 1ns . 1 1735 . 7 1735.7
I I
9 ltOIITHS 100:I. 122/221 I 951. 121/221 I 990.8 9911.8 126).5
I I
lt 110Hl HS 961. lU/Hl I nr. 125/Z71 I 271.S 352 . 7 419 . t
I I
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
...
0
0
l/1
·""
I
Table 2
PATIENT COUtlT CllKlC&l CONPlAlNTS
IIECottBltlAHT 11£PATITIS 8 VACCINE
STUDT I 0795
TREATl1EKt
LOT HUIIMlt I CJ6Z5
DOSE 10 11C&
PATIENT cuss• HEALTH CARE PEltSONttfl
I TOTAL YACCINEES I 30 PATifNTSI - DOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUMIIER
ClIHJCAl
COtlPLAIHT!
l----------------------------------------------------------------------------1
I O I l I l I 3 I " I 5 I
MITH
lt0t1PlAIHTS
••~••••••••••••••••••••••••••ADM•••••••••••••• l•••••••••••••••••••••••••••••••• l•••••••••• ••De•••••••l••••• ..••••~•••••a•••
I I I I I I I I
REACTJOtf, LOCAL CIHJECT. snu I 5 I 2 I l I I I O I O I I 6
I I 11.2;0 I I •• '97.) I I l,41.1 I I 0.07.1 I I 0 . 07.) I C ,.o;o I I I tD . T/.1
-----------------------------------1----------
PAlN I fl
----------1----------
l I o ----------1----------1----------
D I O I O
----------1I -----------
4
11.!llO t 3.4?.I I t 0.01.1 t 0.07.1 I l 0.07.1 I t 0.07.1 I < n.11;0
I I I I
TENDEIINESS I l O I O O I O I O I l
3.47.1 I O.OZI I I o.o;o ( O.GiO I I 0 . 07.1 I I ,.ox, I I J.4XI
I. I I I
ERTTIIEl1A t REDIIESSI I a l I O e I O I o I 1
0.07.I I J.'47.I I I , . 01.1 I ,. ex, I I 0.07.) I I e.o:o I I J.41.1
I I I I
ECCH~ttOSlS I o 0 I 1 0 I O I O I 1
I C 0.07.1 C 0.07.1 I I J.t,ZI I 0.81.1 f I 0.0lO I I e.OZI I I J.ltXI
---------------------------------··1----------l·-·····---l----------l-·--------l----------l-----·----l----------1---··------
sTST£t1tc I l I l I ,. I l I l I l I I 6
I c 10.17.1 I C 6.97.1 I t U.!17.1 I t ,.,:o I I 3.,l!I I I J.4l0 I I I 20.TI.I
------------------------------------------------------------------------------------------------·----·---·------------------
I .
Ult0l£ IIOOY/GUltR.ll I 1 I
3.4Y.I I
l
C J.4)!) I
1
3.4%1 C
D
o.o;o C
0
o.o:o I •
O.OY.I
I
I I
z
6.97.1
I I
FATIGUE/ME•KNESS I l I
3.4il.l I I
l
S.47.1 I
l
J.47.1 I •
••• 7.1 I
0
0.01.1 I
•
o.o:o I
t
6.9?.I
I
iNFECTJDUS Slt«lllOMES i 0
11.0XI
I
I C
D
0.07.1 I
l
].47.t I •
O.Ol!I I
0
o.oio C
0
0.0?.) (
l
J.41. )
I
NERPfS lAIIIALIS, RfCIJIIREHT I 0 I 0 1 D 0 D l
O.OlO I ( 11 .11.1 I l.'ilO I 0.11.1 I 0.07.1 0.0:1.1 I 1.'47.1
IIE5PtltATORY I 1
I
I 1 l 1 0
' 0 l
J.'47.1 I I J.47.I t ].47.) I J.4)!) I O.Ol!I I O,Ol.J I J.47.I
I 0
IIHJHITIS I 1 I l l 1 D D l
l.47.1 I I 3.47.1 C 3.47.1 I J.47.1 I D.DlO I 0.07.) I J.4XI
-
0
0
0-
"'
Table 2 (cont)
PATIENT CO\MT CLitflCAL CortPLAIHTS
REC01111tHANT HlPATITIS 8 VACCINE
Sl\JIJY 17'5
lREATflENT
LOT l«IMBER CJ62S
DOSE 10 ntG
PATJENT CLA!S HEALTH CARE Pt:ASONtEL
---------·---------~--------------------------------------------------------------------------------------------------------
I TOTAL VACCINf:ES I JO PAlllNTS) - DOSE 1 1
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I IU18E1'
CLINICAL
Cllt1PlAltlTS
l---------------------------------------------------------------------------1
I D I 1 I 2 I J I " I 5 I
WITH
ICOHPLAIHTS
•~•••••••••••••••••••••••H••••n••I•••••••••• •••••••••• ••••••a••••••••a••••• ••••a••••••••••••••••••••••~•• d•••••o•a•
I I
DIGESTIVE SlSTEn I l a O I O O O 1
'.!l.ltlO I 0.07.1 C 0.07.1 I C 0.07.J ( e.o;o I 0.IIXI I J.(ol!I
I
NAUS'1 I l a DI. a D l
I J.47.J I e.07.J C 0,07.1 I I o.o;o I O.OY.I C 0.07.1 I J.'1)0
I
0$IGAHS Of SPECIAL SEH!lt I O O 1 I l l 1 1
O.O:O I I.OlO l J.47.1 I l J.4l0 I '.!l.lt:1.1 I J.lt7.J I '.!1.ltl!I
I
CDHJIINCJlVITIS I I O 1 I 1 1 1 l
I I 0.07.1 I I 0.07.1 I '.!1.47.) I I J.4:'.I I l J ... 7.) I J,'i7.I I C J.(o%1
-----------------------------------1----------l----------l----------l----------1----------I----------I----------I-----------
PEIISOHS WlTlt CDnPUINT!I I 8 I J I 5 I 2 I 1 I 1 I I lJ
I C Z7.6i0 I c 10.JZI I c 17.27.1 I C 6.,;o I c :S.lt%1 I I J.lt7.I I I I J7.9i0
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS MITH NJ CotlPLAIHTS I 21 I 26 I 2" I 27 I ze I ze I I 18
I I 72,47.I I C &1.7)(1 I I eZ.l!l(J I I 91.liO I 1 '6.67.I I I "6.67.1 I I I 62.1%1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS MITH HO DATA I I I l I 1 I l I l I 1 I I 1
I I 1.17.1 I C J.l%J 1 c '.!I.J:-fl I c J.J7.I I I J,37.1 I c J.'.!17.1 I I I '.!I.Jr.I
-
0
::>
-,6
-
I
Table 2 (cont)
PAT1£MT COi.HT tllHICAL tottPlAlKTS
RECOIIBINAHJ ltlPATITIS 8 VACCINE
STVDT 0795
TR[ATlttNT
LOT M11111£11 • CJ6ZS
DOS[ 10 NCG
PATJ[NT ClASSl HEALTH CARE PERSOtML
I TOTAL VACCIHEES I JO PATUHTSI - DOSE 2 I

I1----------------------------------------------------------------------------I
DAYS POST VACCJMATIOH I ~ER
CllHICAl
COl1PUIHlS
l----------------------------------------------------------------------------1
I O I 1 I t I J I 4 I 5 I
MITH
ICOttPLAIHTI
a•••~•••••••••••••••••• .. ••••••..•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••n••••••••••••••••••••••••••e
I I I I I I I I
REACTION, LOCl\l (INJECT. SITEI I 4 I 'S I l I O I O I O I I 7
I C 16.07.1 I I U.07.1 I C U.G7.I I I o.o:o I I o.o;o I C 0.0:1.1 I I I ze.o;n
-----------------------------------1----------1----------1----------
PAIH I 4 I Z I 2
----------
o ----------
O
----------
O
----------1-----------
I S
I I 16.0lO I I 8.17.1 I C 8.07.1 I O.CIXI I 0.0l'-1 ·1 0.07.1 I I Z0.07.1
I I I I
SWELLING I O I o I 1 O o o I l
I C 0.07.1 I I 0.07.1 I C 4.0l'-1 I o.o::o I o.o:o C 0 . 0)(1 I C 4.o;o
I I I I
PllUAJTIS tllt"ltlGl I o I o I 1 o o o I l
I I o.07.1 I I 1.07.1 I I 4.07.1 I 0.0%1 I o.o;n t 0.0Y.I I t 4.0%1
I I I
PARESTHESIA I 0 I l I 0 D 0 0
I I 0.117.1 I t 4.07.} I I 0.0:0 t o.o;o t O.OlO t o.o:o I I 4.17.)
----------------------------------·l----------1----------l····-··-·-l---·------l··-···--·-l--------··l----------l-----------
srsutuc I 1 I l I a I O I o I o I I t
I c 4.0%1 I I 4 , 07.1 I I D.07.1 I I 0.0%1 I t 0.0%1 I I 0.0%1 I I t 11.07.I
WHOLE BODY/GENERAL I 1 0 0 0 0 0 l
4.07.1 I o.o;o ( 0.07.1 I 0.07.1 C o.oio C 1,07.1 4.0%1
FATIGUE/NEAKH[SS I
IC
1
4.0)(1 C
D
0.07.1 I •
0.17.1 I
0
0.07.1 I
D
0.07.1 C
0
o.o;o
l
,.o;o
I
11£SPIRATOll1' I
IC •
1.07.1
1
C 4.07.1 C
D
0 . 07.1 I
0
0,07.1 t •
1.07.} t
0
0.17.I
l
4.07.1
I
RHINITIS I
I I
Cl
0.07.1 I
1
4.0lO I
G
O.Ol(I I
0
11.07.1 I
0
0.01.1 I •
8.0%1
I
4.0%1
I
LAIIYN6ITIS I •
o.o;o I
l
,.o;o I
0
O.DlO I
0
0.0%1 I
0
I .DY.I I
0
0.07.I
1
4 . 07.1
0
COUGH I 0
O.OY.l I
l
4 . 01.I I
0
0.0Y.I I
D
0 . 07.1 I
0
D. OY.I I
0
,.o;;r.1
1
4.0Y.I
-
0
C)
OD
....
I
Table 2 (cont)
PA TIENT COUHT CLINICAL COttPL AlHlS
RECotllINAHT HEPATITIS B VACC I NE
STUOT 07'15
ll!£ATl1ENT
LOT H\JllM lt tJt,25
DOSE I 10 IICG
PAU(HT CLASS: HE ALTH CARE PERSONNEL
I TOTAL YACCIHEES < 30 PATl(HTSI • 0~( Z I

1----------------------------------------------------------·-·-·-----------·-1
I DAYS POST YACCHlt.TIOH I NUl'efA
CLINIC AL
Cot1PLAINTS
l------·---------------------------------------------------------------------1
I O I l I 2 I l I .. I 5 I
WITH
ICOtlPLAIHTS
a•••••••••••••••••••••••••••••• .. •• l•••••••••••••••••••••••••••••••• l•••••••••• ••••••••••• l•••••a•••• l•••••••••••e••••-••••
I I I I I I I I
DIGESTI VE SYSJEl1 I I I O I O I O I O I O I I l
I ( 4 . o::o I I a.ox, I I O.Dl!I I ( O.Ol!I I . I o.o;o I I O.Ol!I I I I fo .Ol!l
I I I I I I I I
NAUSEA Ill 01 DI OI OI I I I I
I I 4.0)!1 I I 0.0)!1 I I I
0 . DXI l I
0 . 07.1 I I
0 . 0%1 I o.o:.o I I I 4 .0:1.1
-----------------------------------1----------I----------I----------I---------- I----------I----------I---------I-----------
PEl!SDHS WI TH COttPLAINTS I 5 I 4 I J 1 O I o I O I I 8
I I 20 . 01.1 I l 16 , 0XI I I 12.IIXI I l 0 . 01.I I 1 O. OlO I I 0 . 07.I I I I 32.01.1
-----------------------------------1----------I----------I----------I----------I ----------I---------- I----------I-----------
PEl!SO!lS WITH HO COffl'LAINfS I 20 I 21 I 22 I 25 I 25 I 2S I I 11
I C 110.01.I I l &'t.OX> I I 88.11%1 I 1100.117. > I 1100.IY.I I U DO.OX> I I I 68. 0%1
---- -------------------------------1----------I----------I----------I----------I----------I ----------I ----------I--- --------
PERSOHS NlTN HO DATA I 5 I 5 I 5 I 5 I 5 I 5 I I s
I l 16. 77. l I I 16. 71. l I I 16. 7X I I I 16. 7X I I I 1'. T/.1 I I 16. 71.1 I I I U.. ?lO
....0::,
-c
-
i
Table 2 (cont)
PATIENT COUfT CLINICAL COtlPLAIHTS
RECOt19JHAHT "EPATITIS 8 VltClH!
ST\JDY 0795
TR !A Tl1£NT I
LOT NUffllER : CJ625
005£ : 10 NC&
PATJEtlT CLASS: HUlTlt CARE l'tltSC»ML
I TOTAL VACCIHEES t JO PlTlfHTSI - IIOSE J I

1----------------------------------------------------------------------------I
I OATS POST VACCJNATl!m I t«m8£1t
CLINICAL
CONPLAIHTS
l----------------------------------------------------------------------------1
I O I l I Z I J I 4 I 5 I
MITH
ICOltPlAIHTS
•••••••••••••••••••••••-a• .. •••..•l••••••••••••••••••••••••••••••••l••••••••••••••••••••nl••••a•••••••••••n~•••l~•••a•a•ee
I I I I I I I I
REACTlOH, LOCAL UNJfCT. SITU I 5 I l I I I O I O I D I I 6
I f Zl. 77.1 I I 4.J7.I I f 8.07.1 I f ,.o;o I f 0.07.1 I f O.D;f,I I I f 26.17.1
-----------------------------------1----------
PAIH I 4
----------•----------
0 I O
----------
O
----------
O
----------
O
----------1-----------
I 4
I f 17.47.1 I O,o:o I I 0.07.1 I O.Ol.l I 0.07.1 I 0,07.1 I I 17.4XI
I I - I
TEIIJEIINESS I 1 0 I 8 0 0 D I l
I f 4.JZI I o.o:o I f t.07.1 I 0.07.1 I 1.07.1 I o.o;o I I 4.17.1
I I I
WAJIHTH I l ol O O o a I 1
I I 4.J:o I 0,07.1 I ( 0.07.1 f o.or.1 I 0.07.I f o.o:o I I 4.ll!I
I I I
SWELLING I l 11 D O O O If
I f 4.37.1 I t+.J7.I I I 0.07.1 f 0.07.I f O.OiO f 0.07.1 I I 8.7Y.I
I I I
PIIURITl!I I ITCIUHG I I O l I D O D O I l
I f O.tlo I I 4.37.1 I f O. Ol!I 4 1.07.1 I I 0.07.1 f D.07.1 I f 4.ll!l
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
srsn:111c I 1 I o I a I o I o I 1 I I z
I I 4.37.1 I I 0.07.1 I c 0.07.1 IC 0.07.1 If O.OXI I I 4.57.l I I c 8.77.1
----------------------
1
--------------------------------------------
I I
'11fOLE BOOT/GENERAL I l I O I o I o I I I l
11.)XI I ( 0.07.1 I t o.o::o f I.OlO I 0.117.1 I I O.IY.l I I 4.JlO
I I I I
FATIGUE/WEAKNESS I 1 I O I O I O I I I 1
4.37.1 I I o.o:f.l I I o.o::o I 0.07.1 I O.DY.I I I l!l.07.1 I f ().37.1
I I I I
lHTECTIOUS Sn«>ROHES I o I o I II O D I l I 1
I O,OY.I I I O.OY.I I f O,OXI C I.DY.I I 0,11.I I ( 4.SlO I f ().Jr.I
I I I I
VIRAL INFECTION, NOS I O I O I O I O I 1 I l
I f O.OXI I I D.07.1 I I O.OY.I I I.DY.I I II.DY.I I I 4.57.1 I I 4.37.1
-----------------------------------1----------l----------1----------I----------I----------I----------I----------I-----------
PERSOHS ~ITH CONPLAINTS I 6 I 1 I O I O I I I 1 I I 7
0
0
I I 26.IY.1 I I 4.JY.l I I D. 07.1 I c I.DY.I I I 0.17.1 I I lo.SY.I I I I 30.'tl!I
-
0
-
I
Table 2 (cont)
PATIENT Cotln CLINICAL COHPLAJNTS
R[CotmltlAHT HEPATITIS 8 VACCINE
STIAJT 0795
TIIEATHOfT
LOT tlUt1BEA I CJ62S
DOSE : lO l1CG
PATIENT CLASS: HEALTH CAIi( PEISCHH!l
I TOTAL VACCIHl:ES I 31 PATlfHTSI • DOSf 3 I

1------------------·-··-····---------·--·---·------·--·---·-··--·-·----------I
I DAYS POST VACtlH-.?lOlt I IMfflEA
CLIHICAL
C0!1PLIINTS
l--·---------·-·---·-----·-·-----·-------·--------·-----L-------------·-·----1
I O I 1 I 2 I 3 I 4 I I I
NilH
ltONPLAIHTS
eaa••••••••••••••••••••••••••••••••l••••••••••l••••••••••••••••••••••••••••••••••••••••••••••••••e•••••••••••••el••••••••••
----·-·-----------·-----·-···-·-···1··-····-··1-··-······1··-··--···1---·------1-·---···--1----------1-·----··--1--··--·---·
PERSONS MITH NO Cllt1PLAIHTS I 17 I 22 I 21 I 2J I 21 I 21 I I 16
I I 7].97.I I I 95.77.1 I 110D.17.I I 1100.07.1 I 1100.17.) I I ,5.5iO I I I 69.67.1
---····--·--···-···-------·-·····-·1----·---·-1--·---·-·-l--····--·-1··········1·-·····--·l····----·-1·-·--···-·1···-·····-·
PERSOHS MITH 110 DATA I J I J I J ·1 J I l I l I I 3
I c 11.57.1 I t 11.s1.1 I t 11.57.1 I 1 11.s;o I t 11 . 57.1 I t 12.e:1.1 I I I 11.51.1
0
:::>
I
Table 3,
PATIENT COUMT IIIIX~HUl1 TEHPEAll\fflE9
RECOl1BlHAHT HEPATlllS 8 VlCCIH(
STIJIIY 0795
TIIUTIIEHT
LOT HUnBER CJ625
DOSE 10 t1C9
PlTlEHT CLASS HEALlH CME PERSOlffL
I TOTAL VACCIHEU I lO PAUEHTSJ - DOSE 1 I

1---------------------------------------------------------------------------------------I
I OATS POST YlCCIHlTIOH I tu!B£R
NAX T(HP(Rlllllf(
10£6 F, ORAL I
1---------------------------------------------------------------------------------------I
I o I 1 I 2 I J I 4 I 5 I I I
MITH
11A>< n:111
ao•••••••••••••••••••••••••••••••••l••••••••••l••••••••••••••••••••••••••••••••l•••••••~••l•••••••••••••n••.,.•••f•a•ao•••••
I I I I I I I I
<99 I 18 I n I u I 21 I 20 I u I I u
I 1 1a.J:i.:1 I I e1.s;,.1 I c eo.e;o I I at+.oio I I e1.o;o I I aJ.3%t I I c 6,.o;n
I I I I I I I I
99 - n., I s I J I 5 I '+ I l I '+ I I •
I I Zl.7i0 I I 1Z,5i0 I I 2O.117.t I l 16.117.1 I I 11.01.I I I U,.T.l.t I I I lf>,tY.I
------------------------1----------1----------1----------1----------1----------1----------1-------------------~-1-----------
T[HP(RATUII( TAIIEH I 21 I ti+ I t5 I 25 I 23 I 24 I I 25
I 1 16.1:i.:1 I I ao.oY.1 I I n.1x1 I I e:s.37.1 I 1 1,.1x1 I I eo.or.1 I I I a,s1.1
------------------------1----------1----------l----------l'---------l----------l----------1--·------------------I-------
tEHPERATURE HOT TAKEN I 7 I 6 I 5 I 5 I 7 I 6 I I 5
' --
I I tl.llO I I H.IY.1 I I 16.7Y.I I I 16. T/.1 I I n.J1.l I C 20,tlCI I I I H.7i0
0
0
-
N
-
Table J {cont)
PATIENT COUNT NAXItt.Jtt TfNS'E.ATUIIES
REC0191IHAHT HEPATITIS 9 VACCINE
:SlWY 0795
TREATHEHT
LOT HUMBER CJ6U
DOSE s 10 '1C8
PATIENT CLASS• HEALTH CAlt[ nRsotelEl
I TOTAL YACCINEU I 30 PATIEHT:SI - DOS! t I

1---------------------------------------------------------------------------------------I
"AX TENl'ERAl\lRl
IDEG f, OIIALJ
l----------------------------------·--·-------------------------------------------------1
I I I 1 I t I J I 4 I S I I
WITH
I tlAl< TENP'
••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••I••••••••••••••••••••••••••••••••••••--•••••
I I I I I I I I
< 99 I 11 I lZ I 1l I 11 I 11 • n • I 1D
• I '"·7.iO I I 66.77.1 • I 76.57.1 • C 61.17.1 I I 64.77.1 • I 66.77.l I • I ss .un
• • I • I I I I
'9 - "·' I 6 I 6 I -. I 7 I 6 I 6 I I e
I t 35.3:0 I I J3.lY.I I I U.SlO I I 38.•;o I I 35.17.1 I t :5J.3Y.I I· I I ~-47.1
------------------------l----------l----------l----------l----------l----------1----------1---------------------l-----------
nNPEIIATURE TAklH I 17 I lit I 17 I 19 I 17 I 18 I I 111
I C 56. T/.1 I t 6D.D7.I I C 56. 77.I I t 61.17.1 I I 56. 77.I I I 60.IIY.I I I t 6D.07.I
------------------------•----------l----------l----------1----------1----------1----------•---------------------l-----------
nNPERATU!E t!OT TAKEN I 13 I U I 11 I U I 13 I 12 I I lt
II <t3.3XI I C 40.07.1 I C 0,37.t I C 41,97.1 I I O.lXt II 40.0lO I I C <U.OXI
-"'
C)
I
Table 3 (cont)
PATltNT COUNT NAXIIIJH lttlfltRATllll[S
R£CClttlllNANT HEPATITIS 8 VACClHt
STUDY : 0795
TRU111f.HT i
LOT t«IMDER I CJ625
DOSE I 10 11CII
PATlfNT CLASS: HEALTH CARE PERSONNEL
I lOTAL VACCIHEH I 30 PATIEHTSI - DOSE J I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCIHATIDH I HUH8ER
NAX TEttl'[RATUIIE
IOH F, OAALI
1---------------------------------------------------------------------------------------I
I O I 1 I 2 I J I 4 I s I I I ""< Uffl'
MITH
aa••••••••••••••••••••••l••••••••••l••••••••a•l••••••••••l•••••••••••••••••••••l••••••••••l•a•n•onea■ l••••a•••~al•••••••••a
I I I I I I I I
< 99 I 10 I u I u I n I 12 I 10 I I 10
I I 71.47.1 I I 1a.,:o I I 85.77.1 I I 92.910 I I as.n, I I 76.97.I I I I 66.n,
I I I I I I I I
99 - 99. • I 4 I J I 2 I 1 I t I 2 I I 4
I I 2&.6i0 I I U.t•Y.I I I llt.]iO I I 7.lY.I I I 1'1.JiO I I 15.ltlO I I I u.n,
I I I I I I I I
ltl - 101. • I
I I •. ,x,
e I o I I I o I o I
I I D.OlO I I O.OY.I I I O.OY.I I I o.o;o I I 7.77.1 I
l I I 1
I I 6.7i!I
------------------------l----------l----------1----------1----------1----------I----------I---------------------I-----------
TEIIPHATURE TAIi.EH I 14 I Ito I 14 I lit I 14 I lJ I I 15
I , 46.r,o I 1 46.7lO I « 46.7lo I 1 46.r,o I 1 46.Tl.t I c 4J.JY.I I I , u.or.1
------------------------I----------I----------I----------I----------I----------I----------I---------------------
TE1tPERATUIIE HOT TAKtN I 16 I 16 I 16 I 16 I 16 I 17 I
I-----------
I IS
I I 53.JXI I I SJ.J)(I I I SJ.JXI I I SJ.V.J I I SJ.JiO I I 56,7XI I I I so.or.,
--
0
-
00115
!lAT-LA.l&
C[JNJCAL EVALOATION OF A RECOMBINANT HEPATITIS B YACaNE
F, Deinhardt •, W, .TU,, O. Zoulek, 8.1.otbeer, Md B. Wlltlee
Mu: von Pettenkofer•l111tltute, 1000 Muncher, %. Wet ern G 111an1
Thirty helllthy, ~ volunteers free of MY HBV 1nerJcers were v cclnated with • raeomblne.nt
hepatitis B vaeclM Ftpoted by Marek, 8nUp Ii Dohme, Wtat Point, PA. Ten LC HBsAg wen
administered Intra muscularly a l Ume 0, e.nd one month later. Seroconverslon rat• and geometric meaa
cvneentratlo!IS cft« 1, i and 3 months ••• compared with an are- and sex-matched control group
or
vaccinated with 20 i,ir plunui. derived vaccine (Merek SIW'p & Dohme) (Tabla ll.
Table 11 Compcrilon or Immune r•ponse Aftw recombincnt v1cc:ln1 and plume derived
vaeelne.
month 1.-oeonverslon antl•HBI <,eom. niMII)
16 mUJ
recombinant plasma recombinant plasma
vaccine nccln vaccine vaeetne
1 27 4-4 I.I 15.2
% TO 15 U,8 5U
3 H ts 21.4 u,u
In the recombinant vaceiM a,oup, 38~ or the total antf-HBI at month 3 wu dlrect • d against the
determinant e or HBIAC, eompe1ted to 3096 In the oontrol group. No lncreua IA uaUbody Utei-s ap.lnst
c&ndlda lllblc'im was found In recipients of the rec:omblnant n.cclne 4 weelcs after the second Injection
as eompared to prenccinatlon levels. No 11rlo 11lck! etrects wve obrlerved In 1111y or the vaccinated
individuals.' ·
D 1nhQrdt F, Jilg , Zoul 6, Lor-b r G, W11sk D. C11n1c1l ev luat1on of a

~cmin nt hiP t1tis B v cetn . In: Vy&JS &N, 01 nst•i JL, Hoofnagl
JK, ds. v1r 1 Htp&t1th nd Li\? r Ph s • Orltndo:&~nt 1nd Straton,
19 I.I :Mlt.
00116
1174 THEt..ANCZT,WOVEMIIEl. 24:'1964
CLINJCAL EVAL'UA TIOM OF Jl. RECOMBINANT T1'0UI 1-lita AHD IIGI DDTmlli-"TlOII O,Tlfl TVO \'ACC);IITIOI,
HEPA t1l1S JIil VACCINE GllOVfl•
Tsill "-"' Mole

W.JILQ B.Loumi.
M.SCHMJDT B. WILSXI! ,-;, Ap(yr) No Sc, .,.. l)'l'I
................... """"'
.SaR11_,,,
G.ZOt11.U f.Dm!MAaDT
MIU 8!11'~Jplcm-, l).f1Jt/(J Atirodi50 t 1117_, ~
l.ccMibilllllt bcpwrill B TIICQllt prepared

~ .... ID M•GaJ·I 17 Jl·ld· S I> :H · hJ·6
Pl->t) C21-J4J
121-JZl
123• 12)
41 JS•0.2•7 2) :M•1tS·O 10 :15••&2·)
Pl•D) (ll•12)
hom 1111igca apreued ill ,aer Wl!IJ pvaa 10

30 blflhby ynng YOhwem. $crCICOllftnioa me IIDd uti-
HB1 Inda were ciompm.d 'f1i1h dlaa!t iD II contrOl poap y-.,_
madied for c 111d tG ..-iio liad rnw4 ~
INp,titia I ¥1CCU1e. t .,,._ after die dalrd immull.iaolioll 1'1at a binen• Mpllinn I -=ciDe - pnpared by Mercie
Sllarp I: Dltam raarcla lllbarllaria (lot tWCJ 625). 11 c.aim
results ftrt aimillr ill die rwo poapa. Ia rite nmmbillur .r ,uri6ld HJlaAu, __,,,. MIio pn,ducinl ID n.:ombinaiu
ni:cinc pup Ille immum l"lllpDIIR dc9Claped an alowly
durins lhe corly pbac eel MtOCDn"'1ioa ma 1111d IIIC8II
Senuwllld . .llell eellwnieium~. I ml
-.illlld lO,coOillaAg. ...._ftCll:inc_llM~_,(b
•-cine
1111ti•Hl1 k¥c1I were alipcly lower ill llllla; lbia pn,bllll7 77J/801•21 C-f 7Jl-2 MffllSlllrp tt Dallmt). Subieca in die atlldy
rellect• Ille 0(1 lower doet o(rec:DlltbilUlnt na:ille (lO fill .,..., rcawd 10111 ti, I.,..,. 9ICCillC imrms11K111arly 110,
omparod 'lrith 20 /Ill o(dle plmma ftC!Cim). SidHft"ecu wrt 1; • • aedia; lllbiecu ia • mma1 r,oup ~ io III or
slight Uld 111tibody titra ll!lillll c....
•ltiatru W&:n II« pl-• .tc::wt - - • die - inra-nll. (Sina die
nco1DFD•' tlCalll - a..1111 widlforalill ealy, llldDCK ..-ilb
iDcrcaed ill rccipiaw or tbc recombiDut ftCCiZlc.
p,:psia ....... • - illNsllylliwpi tobe- ~
mao dlt , . _ 'IICC:ine.J llood _ , _ . _ cakCll c , . 11ay of
laCl"Macd:Nl dlit fin- no:iffl? -ad tbim IIIGIDCltlJ, Su~ 'lftR asked IO ltetp
CUUEJ-, bepetilia B YICl:ina 1n effective md ..re. 1 uily , _ . ff body !llllplrlhft wt MNff'ecu ror 5 _, afu:r
H-rvcr, beauac they ere prcparod from pmma o(b\llUD ac:b iajcaiea.
!lq,ati1is B -rinu c:vricra, aupply is rauiaal by die lllll!Allnt
ofplama availtblt and bJ dac cea efpuri{Jing rile lacpeutie 8 S--0
awfle'f u1isen (His.Ag) co raider k fm f'Tolll bepuis 8 HIIAI, lllli-Hla, end an-Hie - t Nied \Ir ndioimrn11no-
ffUI 111d otber possible inl'ecdoua a,cara. Thus. co lllffl die - , wilJi -cially nailabk kill ("Al'SRJA D', 'ACSAJI',
~rldwidc Dad for bcpllitis 8 na:inc, _,, maA1 or 'COit.Ai', Allbal1 Llbnnaoria). Aai-Hla _,ciam in n:11
prcpantion are required. Lady, ~on canyins lbc I>NA ~ CIIQllalll by die -.tliod ol°Holliapr a die lint nm s1.•
IICqUIIICle tor HBIA(! wre prepmd' 111d die 1111iaca '11!!1 n f - p,tpnlioo 1917-, UIII iii I diMioo o( 1:400. 7
8 - S ,.,.,._ 111d C on.- .._ CDIIIIIIOII ■Dliefflit
apra,cd in &be }'all ~ F J l l l ""'1iMLJ Y.a Ol1Js
ilalnlWllllll.1 lllti1lndias . . - C ~ _ , dn8111iDc1 ~-
•anblew H&Aa pol1JICPCicla imoportidts limllalrrotbe paiw liar pin■IMID in 26111~ 1111 dayO Mid 4 •'ftb after
22 1U11 penides round ill blUIIIII plama; Jaaii HI.Ag, dlc lffllod IDd dliNl illjlctiam ol rsombillSllt fltt'int. Stn -.·ert
bownu, ulillc hwmn HB&Aa ie . i ll)'Clll}'lattd. A ncciDc mmiieed far IDtiladilu ,piilll die ilaerminan1 • of HB$A& IS
cle¥cloped hm yun Ka.A, aimubuid aullody pl'fflllllllydllcritlld.'
p,oduaioa ill mice, lriwt IDOlakeyll. met cbimpuze"\; wl
'1bm \'IICCWEIII d!unpu!ll"PS we cllalleDaed wit!a lalllillD llesuu
llepa1itis B YirUS of dilfermt 111btyp&l, cbty nre cmnplccely bocoavaaioa nna mdlDC!Jn anu-HBa levels dutiDS 1bt
prcxcald.' We DOV rcpon me immuniBlaioa or 30 bakby COWllt of'immllllilation . , mown in table 11. Tht immune
:,ow,1 YDhamecn widi lbc finr blpalilil I \rlC:Ci8e pn,cluad rapollllC in tbe ncombiaallt ncc:iDe pwp ,-u lcu
by ncoaabillat DNA itcllnolos,. pronowad dvriq die first IIIOIIW wn in tM pl■ ma
vaccim sn,up, • lbon by lower MroCDDvcnioll r11a and
k,,r;v mcu mri-Mla lfftla. Tllae diff'eraic:a bec-amc aon•
.S,,6jcu lipifiauu alia tbc b.loslu dosu1 monlh 6 v.-hai 29 our orlO
111bjccu (97') were anti-HI, poahm (CDnuol, 41 0111 of .a I)
lO ltalthy IIIWidiail ltlldrma 1111d ltlllr.ra11y t:1tllcn wwt lll!died "1i1b a g--,;c: 111c.1111 wi-HII Ind of21JS IC/I (mn1rol,
(17 (111111&, 13 male; lillllll t 25:d Jr, l'lill[Pl :n->4). Subiaclo in . 4299 IU.11). All uti-Hlf·,otiriwe illdi¥Uhial1 in tht
ds2 COAtrol l'OIII' bad bmi UDllllllliaed eidl ~ 'WIICCiDc rK'IIIIDbilumt ftcciae peup bed uti-HB1 nl11t1 above 10
ill Ill ll!llicr 11udr, 1 dlt7 wrt anadle!! by eat a,,c! ISII IO I.be ervdy
s,oup (rdllt I). Man w:teillaioA. ell aubima art ll/ii1A~ ~ IU/1; 2 (6• ) ftH low rapoeden (lllli-Hla below 100
HBU\s, lllli-Hl1, • amibdi1111 llJ8iu kpmili!. I ec1t enci,:rai run>, , (1~) 'l\'ffC ilnennodme. raponders (lnli•HBs
(l!llli•Hlk), and dl:lir llllliuln:naam kn!o - • 11:111111!ll (81 ilitl 101-1000 IU/1), wl 22 (73·3Q,J ~ iaonnal 10 bigti
end cpcu:rc lliWIO!ransl'cr ~17 - i (tt n111. r1mp:::n~ly). respooden (arui-Hla C!fcmer lhan 1000 run~ Similar valua
Jil 0 ~, Scooi~t ~. Io~1Gt ,. LOri>QQ~ ~. ~11SkG I, DQifth nit f. Clinic l

~v luQtion @fa f"Qt~in~ni ~Q~&t1t1! ~ vecc1n. Lmncot l~M. 2:117~-s.
00117
THELANO?T,NOVEMill24, 191<1 1175
TAIIU D-IMMUNII IIIISl'ONSIS Al'TSI VACCINATIOtl aubiffls immuniaed ,irith a llllllller doK (511a)orconvcn1ional
nmne Oil(! W, Zacbo\'ll R, Schmidt M, Deulhardt F,
.....
S..-""'8ia ,~, A,u~HI, ffUII)•
,.__
1&11publillbcd), 1111d 1111)' rdJ&ct Ille llllC of amailcr IICIOIUIU or
or boch tlCIOJDbinant ftc.cinc and
-
omigaa. ADtipD caatcm
.......
---
~
---
~II!
llem,,ikiaom pfflllld
plama«ri'ftd \'8CCinc iadacrmincd • HBIAg protein. Tbc
Mo.h ••JO) 1•• ◄ 11 pt YUCiaes art produad ad treated diff'ttmtly, bowrvcr;1•11
I
,.,.,
• (Z1J
~,.,,
ll(ff,I 0 IS <1MlS
rhcrd'ort limilar pl"OlciD QICIICDI cloa DOI DCc:a&arily mean
eimilar ilnm11D01miary. The yast and plasma derived
.,
z 21 tlQI !l <0•O'J
J
aam,
.,, "51 2'
u
led " <0·O'J HBs.Aa dilrcred ia ,activity in radioimmunoawy tats; the
reactivity oftbt HBIAB produced ill ,-1 '"' only 20-SO'Vo
◄
! lillJ,/
Jt (15,1
:n,
ZIil <0·OS
<O•O, oftbc raccivirr olplasma-dcrilled HBL4.&.' Tbua, ,·e:1h1•
•
JI~
" ror•Weipc tJla UIUftWIOpllic:ity or chc recombinant \'ICcinc
"'' <O·OS
Jttll,SJ ti)
7 1'"11 4 l(IIOJ 21M 4M >0•0'!
seans ro be less than dial of rhe plame-ocrived vaccine.
0
Aeu-Hiailpa•dlce-tnr-•~aly. Aoodicr ap1aaatioa fot rhc Iowa immu.ac response may be
t'lrllcac·,,-- - . dw 10 ,as of ncoabmm nccine - sifffl per lin&le dose
. TAIIU 111-IWl~"NI! IUISPO!m!S DI MAUlS AND l'llMAUSCAl'Till cvmpand with 20 ,.. or plama-cleriftd YICCUIC. A highc:
TNIIIII DIOCIIIJITIONlll dDlt (20or4014) of'che nacombiDanr Yll:cinc wowd probably
give &be IIIIDe ,awn Ill rhc plaunt-derind YecciDe.
- il....-a
ftlC'Qll:I
~
ftCciltt ,. Dapiic me lliptJy ~ immwlity achincd with the
recomhinem ftCCine, pracecuon will probably bt IS Sood as
M,,/c
widl rhc Clllevaltioaal na:ine, in that all 29 111bilcts with
S.,-niDf'ii.'t UIUlll1J lll/ll(lq
cklealblt ami-HB1 bid Yllua lboft lbc pracemoa level of
Am>Hl, C1U111$. t ll JIM <0· 09
,....., JO IU/1. 11 ID 73"9, 1A1i-HB1 lcnlurtcr the third ncciJlation
were mare than 1000 run; rhia bas been shown to persnttt
Sc, ....... ~ l'Jf17tl00} 2l/21(1,.,
Aau-Haa(f1;11)$ J.ltU 4NO >t•09 pcniltcnct ora1i-HJ11 aboft the procectiff limit for 11 lrast
3 yan. 1• ID edd.itioat all allbjccu wbo 9ffllCOnnrtcd hid
Ulti'bodie qlialt tbc almSD01l determinant • or HIL¼,
illdicatislg aoa-proccaioo qainlt iatecdons widl ocher
111lx:,p111 ol Hla.Aa, Sidt-clrects alter tbe NCOmbinant
\IICCille Witt 11e&ligiblc UICI did DOt difl'tr from tbosc
were obtained in the Cllmrol group. Althoup tile immune obscncd lficr Jllama-dcriwd YICQJIC. The abscnct of a rise
raponsa &0thctwo 11aa:ina wcruimilaraftcrrhcfuDco~ in llltibodie 11wm
C aA,im,u indicatll WI no crou-
of ilnlnlmisation, NpoDIIII of male ad ftnwc aubjea11 'CICUIII ,a,t uurcns wen pracnt ill 111c Yac.cice.
diff'crcd. In bodl grollpG all dlefflHZICll terOCODYertedand rhe Y1111ae!1MnU. S.U-r.rapm NCMial111ilw1n.
1mmcuic mcon anri•HB• ICYcls did DOI dift"cr lignificmrly ~ - . . . w Ill . . . . M11'. J.,Mu •· fwneau(1r,Jaaut111,
(3212 run " 4640 JUII). HO'll'cwr, in mela rcaiWl(l l'lllla!lel.,111. ta, IIIOO M..._ 2, ¥• Gcrao111.
rccombirumt ncanc the ~awnion me t2' "
J009o, and t i l e ~ man lftti.HB• vu 911 "3194 IUIU,-"CII
run (tlblt w). ,.....
....
I, .,.... F. C... el ...... A_, I ... - Au 0- 1., IIIIJ; 14,
Preliminary tcsta indialrc rJaar rccombimmt ncma, like
the plum&-dcrind m:ciDc, iDdllCC!l amibodiEI! qliut both _" ____ _....,.,....,._.............
J.\'- P,Goo,P,ca-..,,M. Z....J,c;.-.HM...... "1
11-1911;--111-lt.
!'(f(looo,e,
rhc 11 111d rhc i campouenca of His aa1cen. Alier month 3, J.v..._P,..._A.._TJ,-G.MdlD.~ood_....,._,

about 38~ of die aaal IIDli-HJIB W&! direaed agaiml ..,.._,_..,.. _ _ ..,.... _ _ · "-"IIU..., .-:-,o
dctermiAaal& ◄· ......... W'J. ~ U. ~ U. .-_.., DL Mllllr "1, H•-• .\Ill.
"-"-1 _ ._ _ - · K-• lt;.1, In: 171-IO
No impanur lidHll'lft8 ecre obGlned lftcr t. z,,._.a.j,la.-,1-tl.~M.a.-P.P_ _,,._....,,,..
immwiiaatilla with IIMr recambillalt 'ftl:CiM. Minor loclJ _...,...,., _ o. - ..., 112-1,.
qmpr0111$ nac:h 111ar8111imr , - . irdlina, bunailli,and 1li1bt ,......_.,._..,_L ......D. ......... JL. ._•.._•l•wt""••
8WIJliq It tbc iDjeclioo lilt WR reponfid UI~ 24 ofrhc 90 ..,__,..I.,__~..........HJ.,,_.
- -
ltQ; t i l - .
.......,. p,.,..
Ml-• II.••
,.,...,._ 111; . _ _ . .-. NHr \·w•I
iDjmiom. On m, OCClllicm did body 1cmpcraciarc rile lbon , . , . . _ . . _ _ ~ PHO ,_. . . ,.._,tlJI; tflt- it
J7•9•C. ~ T- , o T,f..,.1 ,·,"--1, ...... _,__.,.,,.,.,.c,aJt.1,
Of' 26 ll!b;lm 101111.t, all bad aOtibodiell mast C .i-ru
011 dtif O(tirrcs l'rom l:80 10 1;.320) and 1im:& did DOI iDacuc
aftff ilnmimisetion.
la: T~ -
______
C - t l C . -·
Ta• . . _ _ .._,,_,..,_, ltil: ► Jt .
t . Jib '11',' ~ C . O - . r,.___,X.-AJ, ,__,io.GI.
_....,,.
~ IS,,
171•"-
•-er,--.,"' 111"•·
...,...., ,--•·-·-··''
0-.,, LL . . . _ I _..,, ..... 1NltA11 ...,..,
--ll. . . . . ,. . ., .. _. . ., .__.
Dm11!!21em ... . . . _ ......... CL~IA.N,,lrJll,"--A.A--•-lu.. ,..
. . ....,.,. .. _ , _•.....,._,l~Alaal -. ~ ·• ltll .
Thrtt doCC1I or 10 l'B m:ombimmt bcpawill I nccioc IBVC a,m-n. ·
OOf'OCOflftr'llioD rm ud c-•flffic: 11111CD mri-HBI levda 11,CIEaaa, J,l,q:,e I', Go:,,o::,oo AM.Ola!,--..... ,....__... laO Uni •I
~lllo/f
cimilor to thollf iadumd by rhrte ~ or 20 118 ~lam. '- I I;~ O ► to .
derived YllCCine. The raulm ~ ales>cocnparllble 1ridl ahoee IJ. ti lllll..a-..~U. b r - '111.M,Laa AA. N - - • " 1,..,.,.,
ID: lt,,eam i ......,,_ 11, • l>u .... fl . . " - ' " . _ _ ..
obw- ia lllrge UU!ls or cmmn1ioml vamDiil.11.11 N-,ol. a...,, ....... - . . Dalia,.- 1,01 . ,,._,o
The immuft2 rapome 10 the recombiMD• veccinc, U.Gc..!o,:,A.C..-P, llonar,1111.Pt...,,,-,.,_,.,..Di,._,,..,..i,.......
bow,,et, w,as a llroDI durin 1b2 esrly pbae (1 --6 11111ntb.s)
.,,.. cs_,,...,.. l o : - - . 11', Alln NJ, 141,e,•Ol. 11111. \ '1111 .... ,.,.
I I " " - - - -· .__lf'l,O ,.__, I=•-• ,.,,.., u1:
iD all aubjecu, end ill mnl& IMtlD anti-Hie YOJue were lolll-er -.n.
iD tbe ncombinmt 51oup CYCD MIii' thir cvmpknr C1Nl1<l of 1G Jt;J I r , " ' - AL Z..- IL.,..._ P ,._,,.,. ..,. MI-F•• 1•r••
Ne,::,,•o&.~...i, 1ac:1""3..,,.., M..,_11 D .O,v, ,\kJ w•••
illiuiiwswiticm. ~ r \llu llte OD81p(lrable vidi fa.ndins• in to..-,,,J.
.
0011~
Edward M. Scolnick, Arlene A. Mclean.

David J. West. Jules L. Dienstag,
Eloise Watkins. Friedrich Deinhardt and Wolfgang Jilg
23
Antibody 1md! Clinic11I Responses Among Healthy
Adults to 11 Hepatitis B Vaccine Made by
Recombinant DNA
Currently, all commercial hepatitis B vaccines ere comprised of HBsAa purified

Crom the plasmz or human carriers of the virus. However, the use of recombinant
DNA technolozy to effec:t synthesis ohurfac:e antiaen by a culture ofmic:roorpa-
isms is an attractive alternative to infected human pluma u a soun:c of HBsA1
for vaccine. Good expression of the aene for HBsAg has been effected in yeast
(IJ.
Recently, antiaen purified from fermentation cultures of a recombinant strain
of the yeast, Saccharomyc,s ctrtvi'siae containing the aenc for the adw subtype
of HBsA1 was formula1ed into a vaccine throuah absorption on alum adjuvant.
Two methods were utilized for the purification of the HBsAg. Immune affinity
chromatOIJ'&l)hy uses specific: antiaen-antibody bindin1 to effect purification. while
the second method, hydrophobic: interaction chromatography followed by gel
exclusion chromatography, depends upon the selection of water-immiscible mol-
ecules followed by sep&r'fltion on the basis of molecular size.
The physical and chemical chancteristics of vaccine made from HBsAa pro-
duced in yust are very similar to those of vaccine prepared with HBsAg purified
from human plum2. Funhennore, the yeut recombinant hepatitis B vaccine has
been shown to be both immunoSenic and protective in animals (2).
We report here the clinical and antibody rcsponKs obtained in the ftrst three
human clinia.l studies of the yeast recombinant v8'c:ine involvin a 10t&I of 101
VIRAL HEPATmS and LMA DISEASE ~hie ,,.. b\' Grvno Ii Straaon
ISBN 0-1081-li?e-5 All righlu o f ~ il'I any to,m """1fWd.
Scoln1ck E, n t DJ, D L tk1ns E, D 1nh rdt F.

nt1b cl rospcni s 1th~ dults to h1p1t1t1s D
'11 CC1fi b in fit Del. In: Vy , 01 fiSUf JL, Hoofn ~1 JH,
di. ~ p& ft~ Li~ r Dis $ • Orl nd@:6f"l!ln Ml Str tton. 118~:
315-ll.
0011q
3115 Scolnicil, Meleen, West. et al
vac:c:inees. Partic:ipMts were healthy, nonpregnant, adult volunteers. At entry,

subjects were nep.tive for all hepatitis B serologjc: markers, had a normal ALT
level, and had not received any other hepatitis B vac:cine.
Partic:ipanu in the studies received II I .0-ml intramusc:ulu il\iection or the
yeast recombinant hepatitis vaccine c:onwning JO 11,8 of HBsA& at O, I and 6
months. The vaccine used wu from one or two lots •. <Lot 93-4 prepued by the
immune affinity c.hromato~hy method and Lot 972 prepared by the hydrophobic
interzction c:hromatop-aphy method.) Vac:c:inee11 were asked to record their tem•
perature duly for S days after each iiuection of vaccine ru,d to report any loc:a! or
systemic reactions that occurTed duri111 that period.
Postvriccination blood wnples were taketi for the determination or hepatitis
B serol()lic: marlten and ALT. 1n additiot\, radioimmunousay for the detection
or antibody to anliaens in an·extraet of ya.st ladtin1 the acne for HBsA1 was
The vaccine was well tolerated. There have been no serious adverse effects
ann'butt.ble to vaccine and no evidence of hepatitis B infection amon, the vac:cinees
(i.e., no elevation or ALT and no antiaenemia,. Loc:al reactions consistina prin-
cipally or mild soreness ar the i,uection site, genenlly lastina 1-2 days, have been
reported r0Uowin1 ~ of i,uections with vaccine purified by the immune
affinity chromatopaphy method (Lot 93') and I69'-259' of injec:tions with vaccine
purified by the hydrophobic interaction chromatography method. Systemic: com•
plaints including fatiBUe, headache, elevat.ed temperature (IOt• F-IOr F, oral),
pstrointestinal disturbance, symptoms of upper respiratory infection Md nose•
bleed have been reponed followin149'-339' of injections (Table 23.1). There have
been no significant increases in antibody to anti1ens in yeast extract associated
with vaccination.
Table 23.J
Clinical Rnponscs amon1 Healthy Adults to 10 1&1 Doses of
Recombillllllt Hepuius B Vaccine Administend at 0, I and 6
Months
Pn,ponion (~) of Vaccinecs with Clinical Complaints
Widlill s Days or Vacciftalioll
Study di Vaccine Lot I> Site Dose I(. .) Dose l (~) Dose 3 (~)
779 934 Local 12/U (IO) 11/15(731 11/15 (73)
Systtftlic 5115 (33) 3115 (20) 1/1$ (7)
972 LOCZII 6'24(25) 3/19 (16)
Systemic: 1124 (4) 3119 (16)
93' Local 19l21(61) 11/28 (39)
Systemic 5128111) ~.1(14)
795 9:M Local 5/25(20) 6/19 (3%)
Sys1clllic $/25(20) 1/19 (5}
00120
HSV Vaccin Ml)d by Recombin nt ONA 317
Tablcz:u
Scroconvenioo Frequencies for Anli-HBa among Healthy Adulu
Receivinf! 1011'3 Doses otllccombinant Hepalilis 8 Vaccine at O, I
and 6 Monlhs ·
Study I Mo. 2Mo. 3 Mo. 6Mo. 7Mo.
m 934 6115 1411.5 IS/I$ 1$/1$ U/14

(.0) (93) (100) {100) (100)
m 7/24 13119 12/14
(29) (61) (16)
792 93-4 11/21 21123 lJ/13
(]9) (91) (100)
795 934 Ill)() 21/30 19/22
(?7) (70) (16)
Antibody responses to JO ~ doses of the yeast recombinant vaccine have

been comparable to those observed in previous studies with 20 J.L8 doses ofv~ine
prepared from pmsma-derived HBsA1. At I month, 2 7 ~ or the vaccinecs
were positive ror anti-HBs. By 2 months, 68~939' or the vaccinces had anti•
HBs, ud at 3 months 16%-1009' were anuoody positive (Table 23.2). The third
dose or vnc:cine t 6 months bu been given to 1$ penons in one of the studies,
resulting ia a more than 25-Cold iacreue in aeomctric: mun liter.
REFERENCES
I. VlllcllZIICla p, Medwl A, Ruuer WJ. et al. Syftlbesill and assembly or hepatitis B vinls
swfacc 11,11tipn pettKlea ill yeast. NaauR 1912; 291:347-lSO.
1. McAleer WJ, lu)'Mlt EB, Maipner RZ, et al. Hlllllllft hcpcllitis B vaccine rrorn
rec:ombinanl }'GMl. Mann 1914; 307: l'78-1.,.
Kb) (4)
...z::
.,...
. .J
:c
a:-
Ot-
-
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>
u. c.,
....,
I- ....
v,Z:
i..i-
1-Z:
0
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00121
TEST FOR NONINFECTIVITY

· STUDY 839
In clinical trials of the hepatitis B vaccine derived from infected human

plasma, one study was specifically designated as a safety study to ascertain
that hepattth B was not transmitted via the purified vaccine. The yeast
recombinant hepatitis B vaccine is not made from plasma, and intact hepatitis
B virus should not be present at any stage of its formulation. H~ver. in
early discussions with the OoBRR, it was suggested that one study be conducted
as a true human •safetya test.
In Study 839, a single 10 mcg dose of vaccine was administered to f1ve healthy
adult volunteers. The subjects were followed serologically for six months.
During that time period, none of the participants developed any marker of
hepatitis 8 infection (HBsAg, anti-HBc, or elevated ALT). One subject
developed a low titer (6.0 mlU/ml} of antt-HBs four months after receiving the
single 10 mcg injection of vaccine. There were no reports of serious or
alarming adverse experiences.
31421/1
1/22/86
,.,,
°'
CICI
►
Q
=
t;;
no122

Study 839.
PURPOSE: To assess the lack of infect1v1ty of the vaccine among

healthy adults who are negative for hepatitis 8
serologic markers.

Lot #972/C-K444 (10 mcg HBsAg/ml)
PRINCIPAL Robert Bishop, M.D.

INVESTIGATOR: Health Services
WP 38-4
SECONDARY E. P. Avancena, M.D.

WP 38-4
erck Sharp and Dohnse
west Point, PA 19486
STUDY LOCATION: Merck Sharp and Dohme

STUDY POPULATION: The study population consists of 5 healthy adults of

negative for HBsAg, ant1-H8c and anti-HBs, have a
nonnal ALT level, have not previously received any
hepatitis B vaccine and have no known risk factors for
hepat 1tis B.
PROCEDURE: Participants receive a single 1.0 ml (10 mcg HBsAg)

intra.muscular injection of vaccine. Vaccine
recipients are asked to record their temperature daily
for 5 days after vaccination and also to record any
local or systemic complaints that they m&y have during
this period. Unexpected or serious adverse react1 ons
~ill be reported immediately to the study physician.
31921/1
1/14/86
00123
Study 839
PROCEDURE: (CONT.) A blood spectmen (10-15 ml) is obtained from each

participant 1-2 weeks before vaccination.
Post -vaccination blood samples are taken at 2, 4, and
6 Mnths. A11 samples are assayed for HBsAg,
anti-HBC , anti-HBs, and ALT at t:1SDRL. Samples may
also be assayed for yeast antibody.
RESULTS: HEALTHY ADULTS:

10 mcg Lot #972/C-K444 at till! zero.
1. Number Vaccinated: S
2. Seroloq1c Results:
One subject developed a low titer (6.0 mIU/ml) of
anti-HBs 4 months after receiving the vaccine .
Refer to Table 1 for ant1-HBs responses for other
time intervals.
Clin1ca 1 follow-up data are available for a \l 5
participants. The overall frequencies of
complaints are presented below.
Type Frequency in %
Inject ion Site 20 (1/5)
Syste111c 40 (215}

complaints. ~aximum temperature data are provided
1n Table 3.
There were no serious or alarming adverse
reactions attributable to vaccination.
31921/2
1 /14/86
Table l
ANTillODY AfSPIIN!lfS FOLLOWING VACCINATION WITH AECONIIIMANT HEPATITIS B VACC IIII:

STUDT l 0839
POPULATIOff HfALlHT ADULTS
DOU : 11 tlCII
LOT : CK4"4
eu:&11tU1 1 Dav o
lNlTIAL. SE.Rot.0811 NthTJVE
I Y. 111TH AHTl-tl8S I Gt1T INIU/HLI I

l---------------------------------------1-----------------------------------------------------I
I I I IIUPONDERS I
Tin! l---------------•-------------·---------l-----------------1-------- ---------------------------I
lttDNTHSt I SIN>• 2.1 I "IUIHL >• 10 I ALL VACCINEES I S/H >• 2.1 I " IIVtlL >= 10 I
oI ..•••••••••..••••••••••••••••••••••••••••
I I
..•••••••••••••••••••••••••••••••••••••••••••••••••~•••••••••••••••a••~••
I I I
I 2 111JMJMS I OX C0/51 I OX I0/51 I o, J I I
I I I I I I
I 4 ttmnHS I 251! ll/41 I Or. CO/ttl I 1.2 I 6.0 I
I I I I I I
I 6 tlONtllS I tSY. ll/41 I 01. 10/41 I 0.9 I 6.t I
I I I I I I
••••••••••••••••••••••.... •••••••••-••••••••••e•e•••••••••••n••••••n•••••••••-••••••••••H ■ oeK•••nnaeae~&a•n•uaao
,,. -
0
1\1
l:::
,.,
Table 2
PATIENT C1JUNT CLINICAL COHPLAtHTS
IECGt9IttANT HEPATITIS I YACCINl
STUDT 1819
TREAfflf.NT
LOT tllllfflH c..,."
DOSE 10 11C&
PATHNT CUSS NULTHT ADULT$
I TOTAL YACCDl£ES I 5 PATIEMTSI - DOSE l I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION • NUtl!lEII
CLINICAL
C011PlAJHTS 1---------------------------------------------------------------------------•
I D I l I 2 I J I 4 I 5 I
~ITM
ICOffl'LAINJS
.............................................. ,.......... l•n••·-••l••·····..·····················••l•n••·..···•lffl ■••····
REACTIOH, LOCAL IIHJECT. SITU •I l
II O
II O
II D I• 9 I• 9 I• II 1
I I H.OlO I I D.OY.I I f 0.07.1 I I D.OY.I I I , ••,o I I 9.0Y.I I I I H.e;o
-----------------------------------1----------l----------l----------l----------•----------I----------I----------I-----------
SORENt:SS I I I O I 0 I o I t I o I I l
I t to.DY.I I t I.DY.I I I 0.0",0 I I O.OY.I • I 0.0)0 • I O.OY.I .I I I l!e.llo
-----------------------------------1---------•----------1----------1----------1----------1----------•-------·
STSTEHIC • t I 0 I 0 I I I O • 0 I
~-----------
• ·t
I t 40.0Y.I I t I.OY.I I I o.o;o I I D.DY.I I I O.DY.I I I I.DY.I I I t 40.IY.I
------------------------------------------------------------· < ·--------------
~OLE 80DT/GENERAL I I!
• I 40.0lO (
0
O.DY.I f
0
o.o:o I •
1.0)(1 I
0
O.OiO ( •
I.DY.I
2
I <ti.I.Cl
I
SW!ATING I
I
l
c 20.0:0 I
0
O.OY.I I
0
O.OY.I I
0
1.0:CI I
0
0.0::CI I •
0.0lO
l
I !$.DY.I
I
fATJGUE/ME#:HESS I l
20.0Y.I I
D
I.DY.I I •
O.OiO I
D
I.DY.I I •
I.DY.I I
e
t.OY.l
1
I 10.IY.I
II
1NTEGUl1EHTART SJSTEH
• 1
H.OlCI I
0
0.0)(1
0
C 0.0)() I
0
1.0%1
0
C O.OY.I f e.11x1
1
I 10.IY.t
UllTICARUltlIVES I
Ir
1
to,07.J •
C I.DlO
0
0.07.1 • II
,.o:c,
II 1
I H.IY.I
IPRUllJTIS/JTCHIN!!
I
I 1 0
• ' • I
•
' I.DY.I f o.o:o
I 1
I C 20.0Y.I 0.07.1 ·C 1.0;(1o.o:o 0.0%) I.D:O C H.t:ct
I ' ' I I
NERVOUS STSTEH I
I
l
I to.DY.I I
0
•
O.D7.1 •
I o.o:o
O.Oi'.I f•. ,:c,
0.1%1 I
0
I
0 1
I 20.0XI
I
V!aTJ50/IIIZZIHESS I
I
l
I
C to.DY.I • I • I.DY.I •
C o.o:o • I • 0.0%1 O,OY.I C 1.IY.I
l
I l!O.IY.I
' I
-----------------------------------1----------1----------1----------•----------1----------•----------1----------1-----------
PDISDHS NJTH COIPLAIHTS I ] I
• II • I I I D I I 0 0 J
0
-
I I 60.0Y.I I I o.o,n 1 O.OY.J I I I
o.1x1 I 1 I o.ox1 I 1 1.1;c1 I 61,DY.I
0
N
"'
Table 2 (Contd)
PATIENT COUNT CLINICAL ClltW'UJNTS
R£COtl9INANT HEPATITIS I VACCINE
STUDY OIIJ9
fflEATtlENT
LOT IU!!l(R Cl(4lo'
DOS( 10 ncs
PATUHT CLASS! HEALTHY ADULTS
I TOTAL VACCJNUS C 5 PATIEHJSI - DOSE 1 I

l---------------------------------------------------------------------------1
I DA lS POST VACCINATlOH • MUt1!1flt
CLINICAL
COHPLUNTS
1------•---------------------------------------------------------------------1
I I I 1 I Z I l I , I 5 I NITH
•cOltPlAIHTS
•••••••••••••••••••••••••••••-•••l•••••••••••••••..•••••••••••••••l••••••••••l••••••--••l•••--•••••l••••••--••I••••••••••
-----------------------------------•----------t----------•----------•----------•----------•----------1----------1-----------
PUSOHS OIITH NO C011PUINTS I 2 I S I 5 • 5 • 5 I S I I !
I t U.07.1 I cuo.o;o I 11011,07.1 I uao.o;o I 1100.07.1 I 1100.01.1 I I t "ill.17.1
-----------------------------------l----------l----------l----------1----------1----------1----------l----------1-----------
PlRso»s tlITH HO DATA I I I O • O I O • I I 8 I I I
• • o.ox1 • c o.o;o • • o.olo • • 11.0~1 • c 0.11.1 • • s.01.1 • • c e.111.1
-
0
1\.1
a-
Table 3
PATIENT COUNT ttlXIHUt'I TfltPEIATIJIIES
RECOHIIINAHT HEPATITIS 8 VACCINE
STUDY r 0919
TREATl1ENT I
LOT NUl19ER I CK•._
DOSE I 1D 11CG
PATlENT CUSS: HEALTHY ADUI.TS
I TOTAL VACCIN[ES I 5 PATl[HTSI - DOSE 1 •

1---------------------------------------------------------------------------------------•
• DAYS POST VACCIHATION • tM!IIIEII
" AX TIE11PERATUIIIE
I DEGF,OIIAl l
1--•-•••••••••••••••-•-••·•••------------•-----·--··-•---·············••••-•••··•······•1
I I I l I 2 I J • • • 5 • •
Nl lH
l11AX UHP
••••••••••••••••••••••••l••..•••••• · •••••••••• · •••••••••• • •••••••••• l •••••••••• · •••••••••• • ••••••••••·•••H••a■•·••aa•aaae
• • I I I • I •
< 99 I • I s I • I s • s I s I • J
I t ao.o:o I 1100.0:0 I I ao.oio I nnt .o:o I nto .o:o I uoo.o;o I I 1 60 .o:o
I I I I I I I •
99 • 99. t I I I o • l I I I o • I I • l
• I o. 0i( J • I 11.1::r.1 I I zo. , n I I 9 .0i(I I I o . o:o I I o.or.1 I I I ZO.0l! I
I I I I I I • I
101 • 101 . , I l I I I O I ti I O • I I I l
I I tl.0XI I I o.0XI . I a .ox, IC 1 . 0::r.1 IC o.ox , I I o.,x, I I I 2 0 . 0 i( I
·-·-···-·---··-··--·····1··-····-··1-·········1··-·······1··········1··········1···-······1·····················
TIEffl'ERAT\IIU TAKEN I 5 • 5 I 5 I 5 I 5 I 5 I
•·········-·
•· S
I 1100 . DX I I 1100.0XI I n eo .1:0 I ClDl. l iO I u ao.o:o I 1111., x, I I nao.0l!I
···········-·---········•····-·-···1········-·1········-·1·--·······1·--···-···1··-····-··1·····-·---·····-··-··1
TEHPERATI.IIE NOT TAKEN I e I o I O I e I I I O I I
--··-·----·
o
I I 1 ,0)0 I I I . 0iO I I I . OU I I e . ox, I I o .on I I o. ex, • I I I . 0l! I
-...,
0
N
. IMHUNOGENICITY/
SAFETY
HEALTH CARE PERSONNll
/HEALTHY ADULTS
00128
SU"MARY -. HEALTH CARE PERSONNEL AND OTHER HEALTHY ADULTS
Persons employed in a variety of health care occupations are known to be at

above-average risk. for hepatitis 8 infection and therefore constitute a
sizeable candidate population for vaccination with hepatitis 8 vaccine.
Initially seronegative health care personnel and -other healthy adults were
selected as a major group in which to evaluate the immunogenicity and
reactogenicity of the yeast recombinant hepatitis B vaccine. To date, 2414
individuals in 36 studies have received at least one 1nject1on of vaccine, and
1442 of these have completed a 3 dose regimen of vaccination. Anti-HBs titers
following the third injection have been measured in 1048 vaccinees, while
clinical reports are available for 990 of these individuals. Titers currently
available in units of mlU/ml for 829 subjects show that the vaccine is highly
immunogenic, with protective levels of anti-HBs (mlU/ml ~10) developed by
96%. The vaccine has been well tolerated with approximately one-fourth of the
vaccinees reporting minor transient complaints such as injection site
soreness, fatigue, and headache.
IMMUNOGENICITY
Table 1 sunmarizes the antibody responses of 1123 health care personnel and
other healthy adults (excludes data from study #880 which compares consistency
lots), who received injections containing 2.5, 5, 10, or 20 mcg doses of yeast
recombinant hepatitis B vaccine at 0, 1, and 6 months, and for whom
post-vaccination test data are currently available 1n units of mtU/ml.
Anti-HBs responses following the third injection of vaccine are shown for 736
subjects, while responses after only one or two injections of vaccine are
included for an additional 387 subjects. At 3 months (2 months following the
second injection of vaccine), 80-89% of the vaccine recipients had anti-HBs
based on a cutoff of S/N >2.1. By 7/8 months (1-2 months after the third
injection of vaccine), the proportion of vaccinees with antibody rose to
97-lOOS. Slightly lower seroconversion rates were observed using a cutoff of
mlU/ml ~10 : With this cutoff, 57-75% of the vaccine recipients had anti-HBs
by 3 months, while 89-97% were antibody positive by 7-8 months.
The effect of log dose level on seroconversion for anti-HBs was analyzed
statistically. The analysis was done using only data from four studies that
each involved more than one dose level, although seroconvers1on rates 1n these
studies (Tables 2, 3) were very similar to those observed across all studies
(Table 1). Over the four studies, seroconversion rate was found to increase
significantly with log dose level at 1, 3, and 6 months based on a cutoff of
S/N ~2.1 (p <0.001 to 0.002). There was no significant trend at 7/8 months,
with 95% or more of the vaccinees positive for antibody regardless of dose
level. (See Appendix l for a description of statistical methods used.)
31241/1
Using data from three of the four studies (titers not available in units of
mIU/ml for study 1794) seroconversion rates based on a cutoff of mlU/ml ~10
showed a significant upward trend with increasing log dose level at 3 and 6
months (p <0.001). Again, at 7/8 months there was no significant trend, with
89% or more of the vaccinees having titers of mIU/ml ~10 at all dose levels.
A regression of log anti-HBs titers on log dose level, sex, and age, for all
vaccinees with mIU/ml data (study #859 excluded because of missing sex and age
data). showed a 11 three factors to be statistically significant at each time
point with the exception of log dose level at 1 month (p = 0.001 for sex at 1
month and p <0.001 for all else). Larger doses produced higher titers.
Overal 1 geometric mean titers (GfHs) of anti-HBs by dose level are shown in
Table 1. At 7/8 months, the GMTs for responders with a titer of S/N >2.1 were
255.8 mIU/m1 (2.5 mcg dose), 245.1 mlU/ml (5 mcg dose), 1264.3 mIU/mf (10 mcg
dose). and 539.0 mIU/ml (20 mcg dose). Among responders with a titer of
mIU/ml ~10, the GMTs at 7/8 months were 295.3 mIU/ml (2.5 mcg dose),
348. 7 mIU/ml (5 mcg dose). 1321.9 mlU/ml (10 mcg dose) and 1021.5 mIU/ml
(20 mcg dose).
Sex:
Table 4 shows antibody responses of health care personnel and other healthy
adults by sex (does not include data from the consistency lots study, 1880)
who received 2.5, 5, or 10 mcg doses of yeast recombinant hepatitis B vaccine,
and for whom test data are currently available in units of mIU/ml. Responses
for the 20 mcg dose are not shown as recipients of this dose were exclusively
male. Seroconversion rates tended to be somewhat lower among males as
compared to females at early post-vaccination times. By 7/8 months, 97-100%
of the vaccinees had anti-HBs (SIN ~2.1) regardless of sex, while 87-100% had
titers of mlU/ml ~10.
As noted in the earlier discussion on dose level, multiple regression analys;s
showed that log anti-HBs titer was also significantly related to sex at all
time points (p = 0.001 for selt at l month and p <0.001 at other times).
Females tended to have higher titers than males when adjusted for age and dose
level.
Age:
Table 5 shows antibody responses of health care personnel and other healthy
adults ~40 years of age and <40 years of age, who received 10 mcg doses of the
yeast recombinant hepatitis B vaccine, and for whom test data are available
in units of mIU/ml (excludes data from study #880 which compares consistency
lots). The sunmary of ant1body response by age is limited to the 10 mcg dose
of vaccine since few adults ~40 years have yet received other dosages. In
general, older individuals responded less rapidly and developed lower anti-HBs
titers than younger subjects. However, by 7/8 months, 91% of even the older
vacc1nees had titers of mlU/ml ~10.
31241/2
00130
first and second injection of vaccine as scheduled, while the third

injection l:las not administered until 11 months after the first
injection. The individual does have a history of allergies.
2. A 26-year old female became aware that she was pregnant after receiving
one injection of vaccine. The vaccine was administered approximately one
month after conception. She experienced a spontaneous abortion at 18
weeks after fetal death in utero. No microscopic examination was
completed on the fetus. The subject previously delivered two healthy
infants without complication of pregnancy. She had no known allergies.
3. A 37 year-old female noted facial wamth and flushing 14 hours after

receiving her first injection of vaccine. Within the next 3 hours she
developed facial urticaria. She was treated with cold packs. The
symptoms subsided and she recovered in 12 hours. The subject was treated
with Benedryl prior to the second and third injection , and had no
post-vaccination reactions.
4. A 23 year-old female developed hives within 24 hours of receiving the

first injection of vaccine. The hives were described as one large 3-4
inch lesion, pruritic, with several satellite lesions on the back, and
several small lesions on the legs. All symptoms resolved by day 4 post
vaccination. Within 24 hours of receiving the second injection of
vaccine, the subject developed small hives on the back, arms. and left
hand. All symptoms resolved by day 4 post vaccination. The individual
received her third injection of vaccine with no evidence of hives. In
the past, the subject developed hives during administration of contrast
dye (for CAT scan). There is no other allergic history.
5. A 40 year-old female developed a few ecchymotic flat lesions on the

lateral aspect of her breasts, bilaterally, 4 days after the first
injection of vacdne. Over the following 2 days the lesions increased.
Vomiting occurred on the third day. All symptoms disappeared over the
next 36 hours, and the subject has remained well. There was no fever,
and wee, Hgb, platelets, and coagulation profile were normal. The
patient has no history of allergies to exogenous substances. No further
vaccine was administered to this patient.
P4ild transient injection site reactions and systemic complaints were reported
following injection of vaccine at frequencies of 17% and 15%, respectively
( Table 8). The frequency of complaints after the first injection was higher
than after the second or third injections. Table 9 lists specific injection
site reactions that occurred with a frequency of ~0.1%, while Tables 10 and 11
show specific systemic complaints that occurred at frequencies of ~0.1%. The
most frequent injection site reactions were soreness (8%), pain {5%),
tenderness (3%) and pruritis (1%). Systemic complaints that occurred at a
frequency of ~1% include fatigue/weakness (4%), headache (4%), nausea. (2%),
pharyngitis (1%), 111alaise (1%), diarrhea (1%) and upper respiratory infection
(not otherwise specified) (1%) (Table 11). A temperature of ~10o•F (oral) was
reported following 3% of all injections (Table 12).
31241/4
00131
A statistical analysis of seroconversion rates as a function of age was done

for recipients of 10 mcg doses of vaccine using only data from studies that
involved subjects <40 years of age and ~40 years of age. These data are
summarized in Table 6. Based on a cutoff of S/N >2.l, the seroconversion rate
over studies was significantly higher 1n the <40- year · age group than in the
~40 year age group at 1 (p <0.001) , 3 (pc 0.021), and 6 months {P = 0.032) .
Similar differences were seen when the seroconvers1on rates were based on a
cutoff of mIU/ml ~10, w1th significance achieved at 1 (p = 0.021). 3 (p ==
0.022), and 6 months (p == 0.047).
The multiple regression analysis mentioned previously showed that log anti-HBs
titer was also significantly related to age at each time point (p <0 . 001).
The level of response was shown to decrease with age.
Persistence of Antibody:
In most of the c 1inica l studies now in progress, antibody titers wi 11 be

monitored for a period of 2 years following the initial injection of vaccine.
At present, limited data are available through 12 months of follow-up.
Table 1 sumnarizes available data at this time point for 415 health care
personnel and other healthy adults whose titers have been measured in units of
mIU/ml. The GKTs of responders with titers of mIU/ml >10 at 7/8 months
declined 2 to 4-fold by 12 months. Similar declines in antibody titer over
this time interval were characteristic of the subset of vacc1nees consisting
of all those with serologic data at both 7/8 and 12 months. Table 1 shows the
distribution of titers at 7/8 months and 12 months, respectively, for health
care personnel and other healthy adults who received 10 rncg doses of vaccine.
Minimal evidence of antibody (SIN ~2.1) was present 1n 98% of the vacc1nees at
7/8 months and 95% at 12 months, while fully protective levels (mlU/ml .?.10)
were present in 97% and 90% at 7/8 and 12 naonths, respectively. Higher titers
(mlU/ml ~100) were characteristic of 89% of the vaccinees at 7/8 months and of
65% at 12 months, while 58% and 25% of the vaccine recipients were fn the
highest titer category (mIU/ml ~1000) at 7/8 and 12 months, respectively.
SAFETY
In general, the yeast recombinant hepatitis 8 vaccine has been well
tolerated. There have been no reports of serious or alarming reactions
attributable to vaccination. Tables 8-12 surmiarize clinical co11plaints and
elevated temperatures reported by health care personnel and other healthy
adults following injectton with the yeast recombinant hepatitis 8 vaccine
(exclude data from study #880 which compares consistency lots).
Five subjects have had reactions that possibly were related to vaccination.
These reactions are summarized below:
1. A forty-one year old female developed headache , swollen face and rash
within several hours after receiving the third injection of vaccine. The
headache and swollen face resolved in one day, while the rash faded over
4 days. No clinical complaints were reported by this individual
following the first and second injections of vaccine. She received her
31241/1
00132
COMPARISON OF CONSISTENCY LOTS

Five lots of the yeast recombinant hepatitis B vaccine were manufactured in a
production setting to demonstrate consistency. Study 880 was conducted to
evaluate the safety and immunogenicity of these cons.istency lots 1n
seronegative health care p_ersonnel. Subjects in this study receive 10 mcg
doses of vaccine from one of the consistency lots ·a t 0, 1, and 6 months. Data
from this study were excluded from the preceding across studies summary for
health care personnel and other healthy adults.
A total of 233 persons have received one or more doses of vaccine in Study
880. Postvaccination clinical data are currently available for all subjects,
while serologic data have been obtained for 227 of the vaccinees. These
include data on clinical complaints for 99 subjects and ant1-H8s response data
for 139 subjects who have received all three injections of vaccine.
Table 13 shows the age and sex characteristics by lot of the subjects
vaccinated in Study 880. Recipients of each lot were fairly similar except
for a preponderance of males among recipients of lot C-L220.
Table 14 summarizes the antibody responses of persons who received vaccine
from the 5 consistency lots. At 3 months (2 months following the second
injection of vaccine), 84% (range 66-97%) of the vaccine recipients had at
least minimal levels of anti-HBs (S/N ~2.1), while 72% (range 59-83%) had
protective levels of antibody (mlU/~l ~10). By 7/8 months (1-2 months after
the third injection of vaccine), 98% (range 92-100%) of the vaccinees had
antibody titers of S/N ~2.1, and 96% (range 91-100%) had titers of mIU/ml
~10. Geometric mean titers of antibody by 7/8 months were 627.6 mIU/ml (range
332.6-1187.6 mIU/ml) for all vaccinees, 742.9 mIU/m1 (range 476.4-1187.6
mIU/ml) for responders with a titer of S/N ~2.1, and 830.B mIU/ml (range
593.6-1187.6 mIU/ml) for responders w1th a titer of mIU/ml ~10.
Cl 1nical complaints occurring during a five-day period following injections
with vaccine from the consistency lots are sunrnarized in Table 15. There were
no serious adverse experiences attributed to vaccination. All reactions were
mild and transient. Local (injection site) reactions were reported following
5-12% of injections with the various consistency lots. The frequency of
systemic complaints following injection from these lots ranged from 3-9%. Ten
to 15% of the injections from each lot of vaccine involved some complaint. A
temperature of ~lOO•F (oral) was reported following 0-3% of injections.
This study and a second of similar design continue in progress.
A statistical analysis is now being done to evaluate differences between the 5
consistency lots of vaccine with respect to seroconversion rates and geometric
mean titers of ant'i-HBs as well as the reported frequencies of clinical
reactions. The results of the analysis w111 be submitted to the OoBRR as a
supplement to this report by the end of March, 1986.
31241/5
00133
SUMMARY OF ADULT STUDIES

The yeast recombinant hepatitis B vaccine has been well tolerated by healthy
adult recipients. A vaccination regimen consisting of three 10 mcg doses is
sufficient to induce fully protective titers of antibody in 97% of the
vaccinees.
31241/6
tol• I
llftllbcdy ~ ,_,,. M!Nllll Care , . . . _ I 111d Otfw M!lalt!IJ MIils li!l!cltlwl119

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(20/3S)
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(51159) "(W,S)
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(G/GJ)
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(41141)
ff . I IU.O 117.3 '2
(15193)
,.
Cffl9l
l,].:4 '111.7 ZIO.I ,s ,0
(22112«1) (21112«1
1!9.5 Zr\. I W.I 91
(:M/35)
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(30/35)
184.5 ZIJ.4 310.9
tt Tale lln:ts - htclMlb ..... ,ts flflr II wt.jeet• ,. SludJ l'!ld .........u .... l"lttlJIOMft 41Nt ffallale ""'' '" tlllhs of SIii.
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$::
00135
Table 2
Seroconversion Rates for Anti-HBs (Based on a Cutoff of S/N ~2.1)

Among Health Care Personnel and Other Healthy Adults Receiving
Yeast Recombinant Hepatitis B Vaccine at 0, 1, and 6 ~onths
(Studies Involving ore Than One Dose Level)
Time I ,Progortion} ~ith Anti-HBs

( onths} 2.5 incg 5 mcg 10 mcg 20 IIICg
l 27 ( 16/60) 28 (54/196) 36 (74/205) 29 (10/35)

3 86 (48/56) 80 (151/190) 87 ( 161/191 ) 89 (31/35)
6 86 (49/57) 84 (154/184) 93 (177/190) 91 (31/34)
7/8* 100 (58/58) 95 (133/140) 98 (148/151) 100 (35/35)
* Includes a number of responses measured at 9 months when that was the

first blood sample obtained following the third injection of vaccine.
Studies: 794, 798, 813, 883
wva/31241/5
1/9/86
0013b
Table 3
Seroconversion Rates for Ant1-HBs (Based on a Cutoff of mIU ~10)

Among Health Care Personnel and Other Healthy Adults Receiving
Yeast Recombinant Hepatitis 8 Vaccine at 0, 1, and 6 Konths
(Studies Involving ~ore Than One Dose Level)
Time I ( Prol!ortion} w1th Anti-HBs

(~onths) 2.5 mcg 5 meg 10 mcg 20 mcg
l 15 (9/60) 15 (25/167) 19 (31/167) 11 (4/35)
3 62 (35/56) 62 ( l 00/161) 72 (113/158) 57 {20/35)

6 70 (40/57) 68 (101/158) 84 (130/154) 79 (27/34)
7/8* 97 (56/58) 90 (102/114) 96 (110/114) 89 (31/35)
* Includes a number of responses measured at 9 months when that was the

Studies: 798, 813, 883
wva/31241/6
1 /9/86
llbh! 4
Antibody ~ H s by S.x M0n9 ~1th Care Personnel and othsr HNlthy Awlts 119ceh1tng
R!calt>lnant Hepatitis I vaccine •t o, 1, .snd 6 lblths
2.§ ll!!:41
11. id th Ant.I .-s mil falU/111
-
I wl th ltntl ..ffJs
5- *CM fllllU/1111} 1. ttl th Anti _....s
10-•
cm ~IU/1111
llot olU/eil All
. - . - s
■IU/eal elU/11111 All IIIIU/11111 Cll!U/ol All
(Noftths)
l'lllllml
~ S~2.1 ?,10 lfacclnen ~2.1 ~10 5~2 . 1 ?:,10 Vaccl..-s S~Z.1 ?,10 5~2 -1 ~10 ~<!CC:lnNs S/~2. 1 ?,10
I F 33 19 1.3 22.3 54J.O 31 115 1.2 10.6 52.8 34 19 1.2 15.6 41.8
(1/21) ('l/21) (16143) (1/43) (U0/418] (18/IJ l8)
A 23 13 o.a 24.6 11.3 23 M 0.1 19.5 ~-' 215 14 0.9 15.1 45.4
(9139) (5/39) (29/12/J) (181124) (108/'.112) (5'1/JIZ)
3 F !O if) 118.4 29.0 61.8 tl 88 35.Z 49.2 69.Z 88 81 ~.e 80.1 100.6
(tel20) (12/20) (l!B/,il) (33141) (21312/JI) (196/241)
A 83 64 16.3 :!i.2 M.O rs 56 8.6 25.2 51.6 89 12 25. J 0.5 12.1

(?D/3$) (231?1) (tO/IZO) (61/120) (Zl'V311) (2241311)
§ F !O 14 23.1 ~.6 "8.9 9S 8B 54.1 JI.I 81.8 95 91 ~-2 m.2 135.S

(11/19) «113/19) (l'l/iel») (351(0) (255/269) (24"'/259)
l'I 84 19 14.8 30.9 45.9 80 61 13.1 31. 1 59.8 93 84 IJ3.8 59.2 18.6
(3lZ/?S) ca/3:8) ('5/118) (121118) (324/348) (291/348)
118 t F 100 100 301.5 ?l>l.5 !01.5 100 t1 550.3 5&0.3 646.1 99 91 1502.6 1615. 1 1816. 9
(D9/l!l) (1918') (:MJ/30) (a,,lO) (225/228) (222/228)
t1 100 ~ m.2 m.2 292.2 9S 81 144.8 180.5 212.t 91 97 ~-0 1011.5 1()3'.CJ
(3'/~} (31139} (81/84) (13184} (ZRnUO) (291/300)
12 f IUD a M.9 ~-~ 1~.4 100 91 239.5 m.s 351.3 94 91 26'1.9 3R5 .048.6
(16116) ue,1,, (23123) (Zl/23) (IM/110) (100/110)
R 94
(29/31)
81
(21/31)
'9.9 1~9.0 189.1 90
(63110)
159
((9/10)
~-• 69.1 161.3 95 e,
(12~!30) (116/130)
155.S 212.3 213.3
....
0
* Table does nol include results for 11 swjects In Study 194 wllose •ntl--Mts responses •Nt .n.allable only In units of SIM.
....
Vol
t Tmht lnc:lucf:es • IIU!!lbfl- of l'flflOnMS a.sun!!d al 9 mnths llhffl lhat us lite first blood saple obt.alned fol1ut1lng tt,e third Injection or vaccine.
W&-1/3/85-31271/l
0(1138
Table 5
Antibody Responses by Age 6roup Among Health Care Personnel and

Other Healthy Adults Receiving 10 111eg Doses of
Yeast RecON!binant Hepatitis 8 Vaccine at 0, 1, and 6 fllonths*+
Age ! ttith Anti-HBi ~T {1111Ulfil1)
Ti llie Gl"OUP A11 Resl!onders
( onths) (Years) SIN~ 2.1 11lU/11l ~ 10 Vattinees S/14 ~ 2. l IIIIU/111 ~ 10
1 <40 32(227/699) 18(129/699) 1.1 15. 7 42.7

~40 16(21/130) 6(9/130) 0.6 11.9 54 .5
3 <40 89(449/503) 78(394/503) 36.7 60.4 86.2

~40 78(38/0) 55(27/49) 11.0 30.3 67.4
6 <40 95(534/564) 88(498/564) 66.4 85.4 104.-4
?,40 87(46/53) 70(37/53) 21.6 40.6 68.4
7/8.,,.,, <40 98(464/472) 98(462/472) 1225.9 1409.4 1446.0
?,40 95(53/56) 91(51/56) 345.7 487.8 586.5
12 <40 96(190/198) 90(179/198 225.7 293.6 375.7

?,40 90(38/42) 89(37/42) 108.4 198.7 223.7
.,,Table does not include results for 71 subjects in Study 794 t:lhose ant1-HBs
responses were available only in units of S/.
+Table does not include results for 32 subjects whose ages are not presently
known.
-Table includes a number of responses 11easured at 9 11U>nths when that ~as the
31121/1
1/9/86
Table 6
Seroconver-s1on Rates for Ant1-H8s by Age Group

(hsed on a Cutoff of S/N ~2.l)
Altt>ng Health Care Personnel and Other Healthy Adults Receiving
10 nrcg Doses of Yeast RecOlllb1nant Hepatitis 8 Vaccine
at O, 1, and 6 onths t
Ti Age Group I (Pro~ort1onl with Titer

( onths) ( Ye&rs) S/~ ~2.1 ti MIU/111 ~10 'lrlr
l <40 35 (131/378) 16 (57/350)

?40 16 (22/139) 6 (8/129)
3 <40 89 (224/253) 79 (181/230)
?-40 73 (43/59) 55 (27/49)
6 <40 94 (250/266) 89 (212/239)
~0 EM ( 51/61) 69 (36/52)
7/Bt <40 H (221/225) 97 {192/198)
~0 94 (61/65) 91 (50/55)
t Includes a number of responses masurecl at 9 110nths when that tms the

f1rst blood salllJ)le obtained foll0tting the third 1nject1on of vaccine.
* Studies: 779, 792, 794, 801, 803, 807, 809, 813, 835, 838, 869, 883, 889
** Studies: As above, but excluding study 794.
ldVi/31241/8
1/9/86
00140
Table 7
Distribution of Ant1-H8s liten at 7/8 and 12 ~onths

Among Health CBre Personnel and other Healthy Adults
Receiving 10 acg Doses of Yeast RecOlllbinant Hepatttis B Vaccine
at 0, 1, and 6 Months
i (Proportion) w1th Titer

Anti-HDs T1t,c 7/8 Months~ 12 Months
SIN ~2.1 98 (498/509) 95 ( 225/237)
11lU/ml ?,10 97 (494/509) 90 ( 213/237)
■IU/1111 ?,100 89 (451/509) 65 (155/237)

11IU/11l ?,1000 58 (294/509) 25 ( 60/237)
* Includes a nUfilber of responses aeasured at 9 110nths when

that WIS the first blood SlfiPle obtained following the
third injection of vaccine.
ldVi/31241/9
1/9/86
Table 8
Percentages of Health Care Personnel and Other Healthy

Adults with Clinical COflls,la1nts During a Five-Day Period
fo11at:r1ng 3255 Injections of Yeast Rec0ff!lb1nant Hepat1tts B Vaccine
T»e of Ccmpl11nt F1rst lnJect1on Second lnJect1on Third lnlect1on All InJect1ons
Local 20 (2~8/1252) 1~ (151/1162) 11 (139/8~1) 11 (544/3255)
(lnjett Ion S1te)
Systemic 19 (244/1252) 13 (148/1162) 11 (90/841) 15 (482/3255)
Any CC!l!Pla1nt 34 (~26/1252) 23 (263/1162) 23 (196/841) 27 (885/3255)
Stud1~s: llt, 192, 794, 195, 798, 801, 803, 801, 808, 809, 813, 816. 835,
838, 839, 860, 869, 883, 889
llHl/1
1/2/86
0
-
0
-
l :,
00142
Table 9
Frequency of Local (Injection Site) C01131laints Occurring
~ithin 5 Days Anlong Health Care Personnel and Other
Healthy Adults Foll01:rin9 3255 Injections of Yeast
RecOliib1nant Hepatitis 8 Vicc1ne
Number of Vaccine Recipients: 1252
Cg la int Number Frequency IS J?

Soreness 259 8
Pain 149 5
Tenderness· gs 3
Prurith 36 l
Stiffness/Tightness u 0.4
Erythaa l4 0.4
Ecchymos·1s 10 0.3
Swelling 10 0.3
Pain on Injection 6 0.2
warnith 6 0.2
Lymphadenopathy. Regional 5 0.2
Arm Fee 1s Heavy 5 0.2
Nodule 4 o.,
Paresthes ia 4 0.1
Papule 3 O. l
Infl &ll&il&t ion 3 0.,
tJUllbness 3 0.1
Studies: 779 , 792, 794, 795 , 798, 801, 803, 807, 808, 809, 813, 816, 835,
838, 839, 860, 869, 883, 889
2427 I-9
1/3/86
00143
Table 10
Percentage (Nulilber) of Health Care Personnel and other Healthy Adults with
Specific Systemic C0111Plaints During a Five-Day Per1od Following
3255 Injections of Yeast RecOlllb1nant Hepatitis B vaccine
Cop:elaint Frequency 1-4Z Cpqplaint Frequency O.l-0.3i

Fat1gueA:leakness 4 ( 138) Arthralg1a, Other 0.3 (11)
Head1che 4 (135) Influenza, OS 0.3 (10)
Nausea 2 ( 58) Abdominal Pa1ns/Cra s 0.3 (10)
Pharyngitis 1 (40) Lightheaded 0.3 (10)
n&la1se 1 (38) Vomiting 0.3 (10)
Diarrhea 1 (35) Prur1t1s/Itch1ng 0.3 (10)
Upper Respiratory Infection, NOS 1 (32) Ruh 0.3 (10)
Chi 11s 0.2 (8)
Flush 0.2 (8)
C061pla1nt Frequency 0.4-0.91 Shoulder Pain 0.2 (7)
Cough 0.2 (7)
Rhinitis 0.8 (26) Bick Pain 0.2 (6)
Dizziness 0.5 (16) Neck Pain 0.2 (6)
Sweating 0.5 (15) Dyspeps1a/Hea rtburn 0.2 (6)
Ach1ness 0.4 (l4) Neck Stiffness 0.2 (5)
J:lyalg1a 0.4 (13) Earache 0.2 (5)
Sensation of Warnth, General 0.4 (13) Lyaiphedenopathy, Cervical 0.2 (5)
Illness, NOS 0.4 (12) Lyaphadenopathy, General 0.1 (4)
Arthralgia, onoart1cular 0.1 (4)
Diminished Appet1t@ 0.1 (4)
Paresthes 11 0.1 (4)
Urticaria/Hives 0.1 (4)
Clay Colored Stools 0.1 (3)
Insonri1a/01sturbed Sleep o. 1 (3)
S1nus1t1s 0.1 (3)
Laryngitis 0. 1 (3)
Studies: 779, 792, 794, 795, 798. 801 0 803, 807, 808, 8()g,
813, 8l&, 835, 838, 839, 860, 869, 883, 889
31211/l
1/3/86
Table 11
FreQuency of Systemic COlilp1a1nts by Body System Occurring ~ithin Five Days Among
Health tare Personnel and Other Healthy Adults FollO\-ling 3255 Injections of
Yeast Recombinant Hepatitis B vaccine
Frequency as % Frequency as S
Body Syste~/COlii>laint (Number) Body System/Complaint (Number)
~hole Body/General 10 {315) f!lusculoskeletal 2 C52)
Fatigue/We kness 4 ( 138) 14ya lgii 0.4 (13)
Headache 4 ( 135) Arthralgia, Other 0.3 (11)
Malaise 1 (38) Shoulder Pain 0.2 (7)
Sweating 0.5 (15) Back Pain 0.2 (6)
Achiness 0.4 (14) Neck Pain 0.2 (6)
Sensation of Neck Stiffness 0.2 (5)
ll'Janath, General 0.4 (13) Arthralgia,
Illness, MOS 0.4 (12) Monoarticular 0.1 (4)
Lightheaded 0.3 (10)
Chills 0.2 (8) Nervous System 0.8 (27)
Flush 0.2 (8) Dizziness 0.5 (16)
Par.esthes1as o. 1 (4)
IntegUMentary 0. 7 (24)
Digestive 3 (103) Prur1tis/Itch1ng 0.3 (10)
Nausea 2 (58) Resh 0.3 (10)
Diarrhea l {35) Urt1car1a/H1Yes 0.1 (4)
Abdominal Pains/
Cramps 0.3 (10) Infect1cns Syndr01t2s 0.4 {12)
V011iting 0.3 (10) Influenza. NOS 0.3 (10)
Dyspepsia/
Heartburn 0.2 (6) Orvans of Special Sense 0.3 {11)
Diminished Appetite 0.1 (4) Earache 0.2 (5)
Clay-co lo red
Stools 0.1 (3) He111c/Lymphat1c 0.2 {8)
Lyniph1denopithy,
Cerv1Ci l 0.2 (5)
Respir1tory 3 (87) Lyniphadenopithy.
Pharyngitis 1 (40) ~neral 0. 1 (4)
Upper Respiratory
Inf ction, NOS 1 (32) Urogenital 0.2 (6)
Rhinitis 0.8 (26)
Cough 0.2 (7) Psychiatric/Beh1v1or&1 0.2 (6)
Sinusitis 0.1 (3) InsOlll'l1a/D1sturbed
Laryng1t1s 0.1 (3) Sleep 0.1 (3)
Card10V&SCU1 r 0.2 (5}

Studies: 779, 792, 7g4, 795, 1gs, 801, 803,
807, 808, 809, 813, 816, 835, 838,
039, 060, 869, 883, 889
31021-l-12/20/85
Table 12
Percentages of Health Care Personnel and Other Healthy .

Adults Yith Elevated lNll)eratures During a Five-Day Period
Following 3097 lnject1ons of Yeast Rec0fflb1nant Hepatitis B ~acc1ne*
COrQl) Tlt!!Deratyn First InJect1on Second tnJect1on Third InJect1on All lnJect1ons
?lOO•f 4 (45/1217) 3 (28/1111) 4 (27/769) 3 (100/ 3097)
~101°F 0.7 (9/ 121 7) 0.5 (6/1111) 1 (7 / 769) 0. 7 (22/ 3097)
~102ef 0.1 (1/1217) 0. 1 (1/1111) 0.4 (3/769) 0. 2 (5/ 3097)
~103ef O (0/ 1211) 0. 1 (1/1111) 0 (0/769) O.Ol (1/3097)
Stud1~s: 119, 792, 794, 795, 798, 801, 803, 807, 808, 809, 813, 816, 835
831. 839, 860, 86g, 883, 889
~ fever. t~erature not recorded, was reported 1n 1~ cases.
31181/1
1/ 2/86
0
-
0
&::
VI
OOHH,
Table 13
Age and Sex Characteristics of Health Care Personnel

Receiving Injections of Yeast Recombinant Hepatitis 8 Vaccine
from Five Consistency Lots in Study 880
Lot Age (Years} Sex ,~1

Number ~ ~ Male Female
C-L215 25.6 3.6 54.2 45.8
C-L216 30.8 &.9 58.1 41.9
C-L217 32.0 10.0 56.6 43.4
C-L219 30.& 9.5 54.4 45.6
C-L220 25.6 4.3 74.4 25.6
3124 I/17
1/21 /86
Table 14
Antibody Responses Among Health Care Pe rsonnel Receiving 10 mcg Doses of

Yeast Recarbinant Hepatitis 8 Vaccine (S Consist ency Lots) a t O, 1, and 6 ftonths in Study 880
Al] Loiscanblned Lo~ C-b~IS Lot C-L216

J with Anti-HBs GHT (mIU/nll) 'I, with Antl--ffls GNT (11IU/111l} 1. ttith Antl...f!Bs GIil (mlU/ml l
Resoond!rs Responders Resoonders
Tiia:e SIH mtu/ml All SIN 1111U/ml S/N inlU/lftl All S/N inlU/1111 SIM mlU/ml All S/M mIU/111
(llonlhs) ::,2. I ::,10 Vacdnees >2.1 ::,10 ::,2. I ?:.10 Vacclnees ::,2. 1 ?:_10 ::,2. 1 :::_10 VacclMes ::,2. 1 >10
25 11 0.9 12.5 49.8 24 13 0.9 12.S 33.0 20 7 0.1 9.3 39.6

(56/221) (26/227) ( 11/46) (64/64) (8/4 1) (3/4 1)
3 84 72 23.9 49.7 73 .2 86 73 31.9 58. 7 95.4 86 76 18.7 34 .Z 45.7

(1 44/17 1) ( 123/111) (32/37) (27/37) (25/29) (22/29)
6 92 7g 32.0 45.5 62.8 86 64 23.0 36.8 71.8 100 100 S1.S 51.5 51.5
(143/156) ( 124/ 156) (31/36) (23/36) (22/22) (22/22)
1/8 98 96 627.6 742.9 830 .8 100 94 591.2 591.2 799.3 100 100 1187 .6 1187 .6 1187.6
(136/139) ( 133/139) (33/33) (31/33) (24/24) (24/24)
!..21 ~L~H Lgt C-b219 Lot C-l220

'& 11hh Ant I ...ffls GHT (111IU/ml) I, wi t h Anti-His Gl'fT (111IUl!!!l 2 I wi t h Antl4ms G!'IT {mlU/11112
Resoonders Resoonders Resoonders
Tiffl! SIN mlU/ml All S/tl ml U/111 SAi 1111U/ml All S/N llllU/ml SIM mlU/111 All S/tl 11IU/1111
(llonths) ::,2. 1 ::,10 Vacclnees ::,2. 1 ?:10 ::,2. 1 ?:.10 Vacclnees ::,2.1 ?:.10 ::,2. 1 ?:,10 VacclMes ::,2. 1 ?:_10
19 8 0.8 14.5 91.2 22 9 0.1 10. 7 36.7 40 21 1. 1 14. 6 63.8

(10/52) (4/52) ( 10/45) (4/45) (17/43) (9/43)
3 84 68 23.6 48.7 77. 4 66 59 9.5 51. 7 63.9 97 83 50.5 55.6 84.8

(32/38) (26/38) (21/32) (19/32) (34/35) (29/35)
6 87 11 27.5 53.5 69.7 90 73 29.7 '18.0 77.2 97 89 39.5 43.2 53 . I

(26/30) (23/30) (27/30) (W30) (37/38) (34/38)
118 96 91 345.8 4 76. 4 593.6 92 92 332.6 612.6 6 12.0 100 100 1012. 0 1012.0 1012.0 g
.....
(22/23) (21/23) (23/25) (23/25) (34/34) (34/34) ....,
""
wa/31271/4
lOR/86
001~8
Table 15
Percent (Proportion) of Health Care Personnel With Clinical
Complaints During a 5-Day Period Following Vaccination With Yeast
Recombinant Hepatitis B Vaccine From Five Consistency Lots in Study 880R
First Second Third

ill.L T~~e of ComQltint lnjectiQn Injection Injection Total
C-L215 Local (Injection Site) 8 (4/48) 12 (6/4&) 4 ( 1/24) 9 ( 11 /118)
Systemic 2 (l/48) 2 (1/46) 4 (1/24) 3 (3/118)
Any Local or Systemic 10 (5/48) 13 (6/46) 4 ( l /24) 10 (12/118)
Temperature ~1oo•F (Oral) 2 (l/45) 0 (0/38) 0 (0/4) 1 (1 /97)
C-L216 Local (Injection Site) 9 (4/43) 5 (2/43) 9 (1/11) 7 ( 7/97)

Systemic 19 (8/43) 2 (1/43) 0 ( 0/11) 9 (9/97)
Any Local or Systemic 21 (9/43) 5 (2/43) 9 {1/11) 12 ( 12/97)
Temperature ~1oo•F (Oral) 0 (0/35) 0 (0/25) 0 (0/6) 0 (0/66)
C-L217 Local {Injection Site) 11 (6/53) 4 ( 2/53) 0 (0/17) 7 (8/123)

System'it 13 (1/53) 4 (2/53) 0 ( 0/17) 7 (9/123)
Any Local or Systemic 23 (12/53) 4 (2/53) 0 (0/17) 11 (14/123)
Temperature ~1oo•F (Oral) 3 (l/38) 3 (l/32) 0 (0/5) 3 (2/75)
C-L219 Local (Injection Site) 17 (8/46) 9 (4/46) ti ( 1/17) 12 ( 13/109)

Systemic 9 (4/46) 0 (0/46) 6 (1 /17) 5 (5/109)
Any Local or Systemic 22 (10/46} 9 (4/46) 12 (2/17) 15 ( 16/109)
C-L220 Local (Injection Site) 0 (0/43) 9 (4/43) 7 (2/30) 5 (~/116)
Systemic 7 (3/43) 5 (2/43) 3 (1/30) 5 (6/116)
Any Loe a1 .o r system1 c 7 (3/43) 14 (~/43) 10 (3/30) 10 (12/116)
~A complaint or an elevated temperature is recorded here if it occurred during any

portion of a 5-day follow-up period.
31241/16
1/18/86
A P P E NDI X
S T AT I S T I CA L 111 E T H O D S
31241/11
1 /21 /86
00150
All tests of s1gn1ficance were two-s1ded at 0.05 s1gnff1cance level.
A. Clinical Complaints
l. The incidence of the various clinical complaints in d1alys1s
patients on the three dose regimen, healthy teenagers and he1lthy
children were evaluated as a function of log dose level using the
~antel-Haenszel Testl for trend.
2. All other differences in the incidences of the various clinical
complaints in dialysis patients due to dose level or regfaen and
in hHlth care personnel receiving vaccine from consistency .lots
were assessed by the Likelihood Ratio Chi-Square.
B. Seroconvers1on Rates
1. The effect of dose level on seroconversion rates 1n healthy
adults, healthy teenagers and healthll children was analyzed over
studies using the Mantel Haenszel Testl for trend.
2. Differences 1n seroconversion rates In healthy adults due to age
or sex were evaluated over studies using the Mantel Haenszel
Testl for heterogeneity.
3. Differences in seroconversion rates due to age 1n healthy
children, dose level in dialysis patients, end vaccine lot 1n
health care personnel were assessed by the Likelihood Ratio
Ch1-SQuare.
C. Level of Response (Titers)

The effect of age, sex, lot (consistency lots only in Study 880), or
dose level (all other studies) in health care personnel and other
healthy adults, of dose level in healthy teenagers, of dose level and
age in healthy children, and of dose level and regimen in dtalysis
patients were analyzed by fitting these variables to a regression
model. Subjects who were negative for antibody to hepatitis B surface
antigen were . assigned a ttter of 0.3 mIU/ml in the an11ys1s.
REFERENCE
1. Tarone RE, ware J: On Distribution-Free Tests for Equality of
Survival Distributions. Biometrike 64: 156-160, 1977.
31241/12
OOtSt
HEALTH CARE PERSONNEL AND OTHER HEALTHY ADULTS
Study 779 - ~est Point, PA - Or. R. Bishop
Healthy adults are receiving 10 mcg injections of vaccine from one of two lots
at O, 1, and 6 months.
Twenty-six adults received two injections of vaccine from lot C-K4~4, and 21
of these received the third injections. Seroconversion for anti-HBs (S/N >
2.1) at 7/8 months was lOOt (17/17). Ninety-four percent (16/17) developed
protective levels of antl-HBs (mIU/ml ~10) at that time. The GMT at 7/8
months for all vaccinees was 808.S mlU/ml and 1124.9 for responders (mIU/ml
~10). Subjects continue to be followed for persistence of antibody.
One person who received vaccine from lot C-1<444 developed a frontal headache
and erythematous papular rash several hours after the third injection was
administered. This individual has a history of multiple allergies. The
reaction was considered vaccine-related.
Refer to the summary on immune affinity vaccine for responses of subjects

vaccinated in this study using vaccine produced by that method.
Study 792 - Boston. ~A - Dr. J. Dienstag
Initially seronegative health care personnel are receiving 10 mcg injections

of vaccine from one of two lots at 0, 1, and 6 months.
Thirty-five subjects have received two injections of vaccine from lot C-IC564
and 32 of these have received the third injection. Seroconversion for
anti-HBs (S/N ~ 2. 1) was 96% (27/28) at 9 months. Ninety-three percent
(26/28) of the participants developed protective 1eveh of anti-HBs
(mIU/ml ~10) at that time. The GMT at 7/8 months for all vaccinees was 531.1
mIU/ml and 826.3 for responders (mIU/ml ~10).
There have been no reports of serious or alarming reactions attributable to

vaccine. Subjects continue to be followed for persistence of antibody.
Refer to the summary on immune affinity vaccine for responses of subjects

Study 794 - Bethesda, MD - Or. H. Alter
Health care personnel and nonresponders to plasma-derived vaccine, who are

negative for hepat1t1s 8 serolog1c markers, are enrolled in study 794. Health
care workers receive 5 mcg or 10 mcg injections and nonresponders receive
10 mcg inject ions of yeast recombinant vaccine from lot C-1<444 vaccine at o.
1, and f> months. Forty-one health care workers received the initial 10 mcg
injection of vaccine and forty of these participants have also received the
24641/1
00152
Study 794 - Bethesda, ~D - Or. H. Alter (Contd)
second and third injections. At seven inonths, 97% (35/36) of the vaccinees
seroconverted for ant i-HBs ( S/N ~2. 1). Ninety-four percent ( 34/36) developed
levels of anti-HBs >10 S/N. The GMT at seven months for all vaccinees was
160.8 S/N and 209.3 for responders (S/N ~10).
Thirty subjects received two 5 mcg injections of vaccine. Twenty-eight of

these participants received the third injection. Eighty-four percent (21/25)
of the vaccinees seroconverted (S/N ~2.1) for anti-HBs at seven months.
Seventy-six percent (19/25) developed anti-HBs titers >10 S/N at that time.
The GMT for all vaccinees was 54.0 S/N and 152.9 for responders (S/~ ~10).
There have been no reports of serious or alarming· react Ions attributable to

vaccine. The study continues 1n progress.
Study 795 - West Germany - Dr. F. Deinhardt
The study population consists of health care personnel and other healthy
adults who are negative for hepatitis B serologic markers. Participants are
scheduled to receive 10 mcg injections of vaccine at 0, 1, and 6 months from
one of 3 vaccine lots.
One hundred forty-eight persons have received vaccine from lot C-K564. One
hundred twenty-six of these participants have received all three injections.
Seroconvers1on for anti-HBs (S/N ~2.1) at 7/8 months was 1001 (76/76). All of
these vaccinees developed protective levels of anti-HBs (mIU/111 ~10) at that
time. The GMT at 7/8 months for all vaccinees was 2143.1 mIU/ml.
Ninety-seven persons have received lot C-L215 vaccine. Ninety-four of those

participants have received all three injections. At 7/8 110nths, 991 (79/80)
of the vaccinees seroconverted (S/N ~2.1) and developed protective levels of
anti-HBs (mIU/ml ~10). The Gf:'lT at 7/8 months for all vaccinees was 2436.1
No serious or alarming r.eactions attributable to vaccine have been reported.

The study continues in progress.
Refer to the summary on immune aff;nity vaccine for responses of subjects

Study 798 - Houston, TX - Dr. f. B. Hollinger
The study population consists of male paramedical personnel who are initially
negative for hepatitis B serologic markers. Participants are assigned to
receive vaccine at one of three dose levels (5 mcg, 10 mcg or 20 mcg) from lot
C-K446 at o, 1, and 6 months.
Thirty-six persons have received the initial 20 mcg injection of vaccine, and
all but one of these have received the second and third injections. Sero-
24641/2
00151
Study 798 - Houston. TX - Dr. F. B. Hollinger (Cont.)

conversion for anti-HBs at 7/8 months (S/N ~2.1) was 100% (35/35). Ninety-one
percent (32/35) of the vaccine recipients had an anti-HBs titer ?_10 mIU/ml
with a ~T for the responders of 1193.3 mIU/ml.
Thirty-seven part1c1pants received three 10 mcg injections of vaccine. Sero-
conversion (S/N ~ 2.1) at 7/8 months was 97% (34/35). Ninety-seven percent
(35/36) of the vaccine recipients had anti-HBs titers of mIU/ml ~ 10 with a
GJlT for responders of 601.6 mIU/ml.
Thirty-six persons have received three 5 mcg injections of vaccine.
Ninety-seven percent (35/36) of the vaccine recipients seroconverted for
anti-HBs (S/N ~ 2.1) at 7/8 months. Eighty-three percent (30/36) of the
participants developed titers of mIU/ml ~ 10. The GMT at 7/B months was 72.9
mlU/ml for a 11 vacc i nees and 136. 9 for responders (mIU/ml ~10). Subjects
continue to be followed for persistence of antibody.
No serious or alarming adverse experiences attributable to vaccine have been
reported. Subjects continue to be followed for persistence of antibody.
Study 801 - Houston. TX - Dr. E. Septimus

Initially seronegative health care workers in this study are receiving 10 mcg
injections of vaccine from lot C-K444 at 0, 1, and 6 months.
Twenty-two subjects have received the first injection of vaccine and
twenty-one of these have also received the second and third injections.
Seroconversion for anti-HBs (S/N ~2.1) at 7 to 8 months was 100% (21/21). All
of these participants developed protective levels (mIU/ml ~10) of anti-Hes at
that time. The GMT at 7/8 months for all vaccinees was 280.8 mIU/ml.
Subjects continue to be followed for persistence of antibody.
One subject ( 26-year old female) became aware that she was pregnant after
receiving one injection of vaccine. The vaccine was administered
approximately one month after conception. She experienced a spontaneous
abortion at 18 weeks after fetal death in utero. No microscopic examination
was completed on the fetus. The subject previously delivered two healthy
infants without complication of pregnancy. She had no known allergies. The
experience was considered possibly related to vaccine.
Study 803 - Denver, CO - Or . G. Judson

Health care personnel, negative for hepatitis B serologic markers, are
receiving 10 mcg injections of vaccine from lot C-K444 at 0, 1, and 6 months.
24641/3
00154
Study 803 - Denver, CO - Dr. G. Judson (Cont.)

Thirty-one persons have received the 1n1t1al injection. Thirty of these have
also received the second and third injections. At 7/8 months, 85% (22/26) of
the participants seroconverted (S/N ?:,2.1) and developed protective levels
(mIU/ml ?:,10) of anti-HBs. The ~T at · that time for all vaccinees was 584.6
mIU/ml and 2136.0 for responders (mlU/ml ?:,10).
No serious or alarming reactions attributable to vaccine have been reported.
Subjects continue to be fo1lowed for persistence of antibody.
Study 807 - The Netherlands - Dr. S. Schalm

Health care personnel who are negative for hepatitis 8 v1rus serologic
markers, are receiving 10 mcg injections of yeast recOllbinant hepatitis 8
vaccine lot C-K444 or 20 mcg injections of licensed plas111a-derived vaccine lot
1510J (HEPTAVAX-8) at 0, 1, and 6 months.
Thirty-one participants have received three 10 mcg injections of yeast
recombinant vaccine. Seroconversion for anti-HBs (S/N?:. 2.1 and mIU/ml ~ 10)
at 7/8 months was 100~ (31/31) with a GMT of 885.l mIU/ml for all vaccinees.
Twenty-five subjects have received three 20 mcg injections of licensed
plasma-derived vaccine. At 7/8 months, seroconversion for ant1-HBs (S/N > 2.1
and mIU/ml ~ 10) was 100% (22/22) with a GMT of 6164.4 111IU/ml for- all
vaccinees.
No study participant reported a serious or alarming reaction attributable to
vaccine. Serolog1c testing continues 1n progress.
Study 808 - Tucson, Arizona - Or. R. Sampliner

Health care personnel who are negative for hepatitis B virus serologic
markers, are receiving 10 mcg injections of vaccine from lot C-K444 at O, l,
and 6 months.
Twenty-five subjects have received three injections of vaccine. At 7/8
months, 96% (22/23) of the participants seroconverted (S/N ?:,2.1) and developed
protective levels (mlU/ml ~10) of anti-HBs. The 6"T at that time for all
vaccinees was 1711 . 5 mIU/ml and 2535.7 for responders (mIU/ml ?:,10).
The vacdne has been well tolerated with no reports of serious adverse events
related to vaccine. The study continues in progress.
Study 809 - Philadelphia. PA - Or. S. Plotkin and Dr . S. Starr

In study 809 healthy adults and healthy children {l-11 years). init\ally
negative for hepatitis B serologic markers, are scheduled to receive vaccine
at O. 1, and 6 months.
24641/4
00155
Study 809 - Philadelphia, PA - Or. S. Plotkin and Dr. S. Starr (Cont.)

Eighteen healthy adults have received the initial 10 mcg injection of vaccine
from lot C-K444. Al 1 but one of these participants received the second and
third injections. At 7/8 months, 100% (11/11) of the vaccinees seroconverted
(S/N ~2.1) and developed protective levels of anti-HBs (mIU/ml ~10). The G~T
at that tirae for all vaccinees was 955. 7 mlU/ml.
There have no reports of alarming or serious adverse experiences attributable
to vaccine. Subjects continue to be followed up for persistence of anti-HBs.
Refer to the summary on infants and children for responses of other subjects
vaccinated in this study.
Study 811 - Switzerland - Or. P. Grob

Health care personnel and predialysis patients, initially negative For
hepatitis B virus serologic markers, are enrolled in study 811. Health care
personnel receive 10 mcg injections of vaccine lot C-K446 at 0, 1, and 6
months.
Eleven health care personnel have received an ln1t1al 10 mcg injection of
yeast recombinant vaccine. Eight of these have received the second and third
injections. At 7/8 months, 86% (6/7) of the participants seroconverted for
anti-HBs (S/N ~2.1). Eighty-three percent (5/6) developed protective levels
of antl-HBs (mIU/ml ~10). The G~T at 7/8 months for all vaccinees was 275.1
mIU/ml and 1076.6 mlU/ml for five of the responders. · Among subjects with
serology data available at 12 months, 83% (5/6) were positive for anti-HBs
(mIU/ml ~10). The GMT for all vaccinees at that time was 44.1 mIU/ml.
vaccine. Subjects continue to be followed for persistence of antibody. Refer
to the surmnary on dialysis and predialysis patients for responses of other
subjects vaccinated in this study.
Study 813 - New Vort, NV - Dr. M. Davidson

The study enrolls health care personnel, some of whom are seronegatfve for
hepatitis 8 virus markers and have never been vaccinated, and others
(preinvnune) who have previously been vaccinated with either yeast recombinant
hepatitis B vaccine or plasma-derived hepatitis B vaccine (HEPTAVAX-B). There
are five groups of initially seronegative adults, not randomized by age, who
are scheduled to receive vaccine from lots C-K444 or C-L220 at 0, 1, and 6
months. These participants receive either 2.5 mcg, 5 mcg or 10 mcg
injections. There is an additional group of seronegative adults, ~40 years of
age, who are scheduled to receive either 10 mcg injections of lot c-~126 or 20
mcg injections of lot C-1'4125 at 0, 1, and 6 months.
Sixty-one health care personnel have received two 2.5 mcg injections of
vaccine and sixty of these have received the third injection. At 7/8 months,
24&41/5
00156
Study 813 - New York. NY - Dr. ~- Davidson (Cont.)

10~ (40/40) of the subjects seroconverted for anti-HBs (S/Pd ~2.1) and 97~
(39/40) developed protective levels of antibody (mIU/ml ?,10). The GMT for all
vaccinees at that tiM was 291.5 mIU/ml and 321.5 for responders (mIU/ml ~10).
One-hundred-twenty-one seronegative adults have received one 5 mcg injection
of vaccine. One-hundred-twenty and 115 of these have received the second and
third injections, respectively. Ninety-eight percent (42/43) of the
participants seroconverted for anti-HBs (S/N ~2.1) at 7/8 months. Ninety-five
percent (41/43) developed protective levels of anti-HBs (mlU/ml ?,10). The GMT
for all vaccinees at 7/8 months was 523.8 mIU/ml and 693.9 for responders
(mlU/ml ?,10).
In the 10 mcg dose group, 131 health care personnel have received the first
injection of vaccine. One-hundred-twenty-four and 109 of these have received
the second and third injections, respectively. At 7/8 months, 100% (36/36) of
the vaccinees seroconverted (S/N >2.1) and developed protective levels of
anti-HBs (mIU/ml ?,10). The GMT- for all vaccinees at that time was
1509.3 mIU/ml.
Seven adults have received one 20 mcg injection of vaccine and four of these
have received the second injection. Serologic data are not yet available for
these participants.
To date, recipients of 10 mcg injections have developed higher anti-HBs titers
than those receiving 2.5 mcg or 5 mcg injections of vaccine.
A 23 year-old female developed pruritic hives on her back and extremities
after the first and second 10 mcg injections of lot C-L220 vaccine. All
symptoms resolved within four days after each injection. The reaction is
considered vaccine related. The subject has a history of allergy to contrast
dye. She received the third injection of vaccine without development of hives.
No serious adverse experiences attributable to vaccine have been reported.
The study continues in progress. Refer to the sunmary on preimmune adults
for data regarding other subjects vaccinated in this study.
Study 815 - Holland - Dr. S. Schalm

The study population consists of institutionalized mentally retarded
individuals and health care personnel who are seronegative for hepatitis B
markers. The health care personnel will serve as controls in this study.
Participants will be paired (mentally retarded and controls) and randomized to
receive either 10 mcg or 20 mcg injections of yeast recombinant vaccine or
20 mcg injections of plasma-derived vaccine. All injections will be
administered at 0, 1, and 6 months.
Sero logic and clinical follow-up data for the health care personnel are not
presently available. ~o serious or alarming adverse reactions attributable to
vaccine have been reported. Vaccination and follow-up of all participants
continues in progress.
24641/6
00157
Study 816 - Philadelphia. PA - Dr. S. Plotkin and Dr. S. Starr

The population consists of three groups of initially seronegative adults:
dialysis patients, dialysis patients who were previously vaccinated with
plasma-derived hepatitis B vaccine and failed to respond, and health care
personnel. All participants are receiving vaccine from lot C-IC44£, at 0, 1,
and 6 months. Dialysis patients receive 40 mcg injections of vaccine, while
health care personnel are administered 10 mcg injections.
Eight health care personnel have received two 10 mcg injections and 6 of these
have received the third injection. At 7/8 months, anti-HBs (S/N > 2. 1 or
mIU/ml ~ 10) was present in 80% (4/5) of the subjects tested. The GMT for all
vaccinees and responders (mIU/ml ~10) at 7/8 months was 37.9 mIU/ml and
127.2 mIU/ml, respectively.
Refer to the summary on dialysis/predialysh patients for responses of other
Study 834 - Italy - Or.~- Rizzetto

Initially seronegative healthy adults are receiving 10 mcg (1.0 ml) injections
of vaccine lot C-K564 at 0, 1, and 6 months.
Twenty-five subjects have been enrolled in the study and have received one
injection of vaccine. Serologic and clinical follow-up data are not presently
available.
There has been one report of an adverse experience considered possibly related
to vaccine. A 40 year-old female developed a few ecchymotic flat lesions on
the lateral aspect of her breast, bilaterally, 4 days after the first
injection of vaccine. Over the following 2 days the lesions increased.
Vomiting occurred on the third day. All symptoms disappeared over the next 36
hours, and the subject has remained we 11. There was no fever. and WBC, Hgb,
platelets, and coagulation profile were normal. The patient has no history of
al lerg1es to exogenous substances. No further vaccine was administered to
this patient.
Study 835 - Chapel Hill, NC - Or. S. Lemon

Health care personnel, who are negative for hepatitis 8 virus serologic
markers, are receiving 10 rncg injections of vaccine from lot C-K564 at O, 1,
and 6 months.
Twenty-nine subjects have received the first two injections of vaccine, and 23
of these have received the third injection. At 7/9 months, 100% (19/19) of
the participants seroconverted (S/N 2.1) and developed protective levels of
anti-HBs (mIU/ml ~10). The GMT at that time for all vaccinees was 560.9
mIU/ml.
Study participants have not reported any alarming or serious ad°verse events
related to vaccine. The study continues in progress.
24&41/7
OOiS8
Study 838 - ~est Germany - Or. F. Deinhardt

Populations vaccinated in this study include health care personnel and adult
dialysis and predialysis patients. Health care personnel are receiving 10 mcg
injections of vaccine from lot C-K733 at 0, l, and 6 months.
Twenty-two health care personnel have received the first 10 mcg injection.
Nineteen and 17 of these have received the second and third injections ,
respectively. At 7/8 months, 94% (16/17) of the participants seroconverted
(S/N ~2.1) and developed protective levels of anti-HBs (mIU/ml ~10). The GMT
at that time for an vaccinees and responders was 284.8 mJU/ml and 437.1
mIU/ml, respectively.
There have been no reports of alaming or serious adverse experiences
attributable to vaccine. The study continues in progress. Refer to the
sunmary on dialysis and predialysis patients for responses of the other
Study 841 - London, UK - Dr. A. Zuckennan and Or. I. ~urray-Lyon

Initially seronegattve health care personnel are receiving 10 mcg (1.0 ml)
injections of vaccine lot C-K563 at 0, 1, and 6 months.
Serologic and clinica l follow-up data are not presently available. No serious
or alarming adverse experiences attributable to vaccine have been reported.
Study 859 - Belgium - Dr. N. Clumeck

Health care personnel are receiving 10 mcg injections of yeast recombinant
vaccine from lot C-K563 at 0, 1, and 6 months.
Thirty-one persons have received the first two injections. One month after
the second injection, 80% (24/30) of the vaccine recipients were positive for
anti-HBs (S/N > 2.1). Fifty-three percent (16/30) of the subjects developed
protective levels of anti-HBs (mIU/ml ~10) at that time. The GMT at three
months for all vaccinees was 11.8 mIU/ml and 60.0 for responders (mIU/ml ~10).
There have been no reports of serious or alam1ng reactions attributable to
vaccine . The study continues in progress.
Study 860 - Hamburg, Mest Germany - Or. R. Laufs

Health care personnel, initially seronegative for hepatitis B serologic
markers, are receiving 10 mcg injections of vaccine from lot C-K564 at 0, 1,
and 6 months.
Sixty persons have received the initial injection , and 59 of these have
received the second and third injections. At 7/8 months, 100% (56/56) of the
participants seroconverted (S/N ~2.1) and developed protective levels (mIU/ml
~10) of ant1-HBs. The GMT for all vaccinees was 2421.1 mIU/ml.
24641/8
00159
Study 860 - Hamburg , ~est Germany - Dr. R. Laufs (Cont.}

vaccine. The study continues in progress.
Study 869 - Toronto , Ontario - Dr. J. Rankin

The study population consists of seronegative health care personnel who are
receiving 10 ~cg injections of vaccine from lot C-L217 at 0, 1, and 6 months.
Seventy-one participants have received the first two injections of vaccine.
At one month, 32~ (22/68) of the subjects seroconverted (S/N ~2. 1) for
anti-HBs. Twelve percent (8/68} developed protective levels of anti-HBs
(mIU/ml ~10} at that time. The GMT at one month fo r all vaccinees was 1 .2
mIU/ml and 44.8 for responders (mIU/ml ~10}.
Study 877 - Republic of Singapore - Prof. Oon Chong Jin

Healthy adults, who are negative for hepatitis B virus serologic markers, are
receiving 10 mcg injections of vaccine fro~ lot C-K564 at 0, 1, and 6 months.
Thirty-one subjects have received all three injections of vaccine. At 7/8
months, 97% (28/29} of the participants seroconverted (S/N ~2.1) and deve l oped
protective levels (mlU/ml >10) of anti-HBs. The GMT at that time was 508.9
mlU/ml for all vaccinees and 663.7 for responders (mIU/ml ~10).
There have been no reports of ser1ous or alarming reactions attributable to
Study 880 - Valhalla , NY - Or. G. Wormser

Initially seronegative health care personnel are receiving 10 mcg injections
(0 . 5 ml) of vaccine at 0, 1, and 6 months from one of the following
consistency lots: C-L215 . C-L216, C-L217, C-L219, C-L220.
Forty-eight subjects have received two injections of vaccine lot C-L215 and
forty of these have received the third injection. At 7/8 1110nths, lOOS!; (29/29)
seroconverted (S/N ~2.1) for anti-HBs and 93% (27/29} developed protective
levels of antibody (mIU/ml ~10). The GMT for all vaccinees at that time was
602 . 9 mIU/ml and 853.6 for responders (mIU/ml ~10).
Forty-three subjects have received two injections of vaccine lot C-L216 and
eighteen of these have received the third injection. At 7/8 months, 100%
(10/10) seroconverted (S/N ~2.1) and developed protective levels of anti-HBs
(mIU/ml ~10). The GMT fo r all vaccinees was 986 .9 mlU/ml .
24641/9
00160
Study 880 - Valhalla, NV - Dr. G. Wonnser (Cont.)

Fifty-three participants have received two inject;ons of vacc tne lot C-L217.
Twenty-six of these were administered the third injection. Ninety-one percent
(10/11} seroconverted for anti-HBs (S/N ~2.1) at 7/8 months. Eighty-two
percent (9/11) developed protective levels of antibody (mIU/ml ~10). The GMT
for all vaccinees at 7/8 months was 331.1 mIU/ml and 1157.1 for responders
(mlU/ml ~10).
Forty-six adults have received two injections of vaccine lot C-l219 and
twenty-one of these have received the third injection. At 7/8 months. 100%
(11/11) seroconverted (S/N ~2 . 1} and developed protective levels of antibody
(mIU/ml ~10). The GMT for all vaccinees at that time was 583.4 mIU/ml.
Forty-three participants have received two injections of vaccine lot C-L220.
Thirty-eight of these have been administered the third injection. At 7/8
months, 100% (29/29) seroconverted for anti-H8s (S/N ~ 2.1) and developed
protective levels of antibody (mIU/ml ~10). The GMT for all vaccinees at that
ttme was 1009.9 mIU/ml.
No serious or alarming adverse experiences related to vaccine have been
reported. Clinical and serologic follow-up continues tn progress.
Study 882 - Tokyo, Japan - Or. S. Iino

Healthy adults, initially negative for hepatitis B serologic markers, are
receiving 10 mcg injections of vaccine from lot C-L215 at 0, 1, and 6 months.
Forty adults have received all three injections of vaccine. At 7 months, 10~
(40/40) of the vaccine recipients seroconverted for antf-HBs (S/N ~ 2. 1).
No serious or alarming reactions related to vaccine have been reported. This
study continues in progress.
Study 883 - Philadelphia , PA - Dr. S. Plotkin and Dr. S. Starr

Initially seronegative health care personnel are receiving 5 mcg or 10 mcg
injections of vaccine from lot C-L220 at 0, 1, and 6 months.
Twenty-five subjects have received two 5 mcg injections of vaccine, and 24 of
these have received the third injection. At 7/8 months, 100% (20/20) of the
participants seroconverted (S/N ~2.1) for ant1-H8s. Ninety-five percent
(19/20) developed protective levels of anti-HBs (mIU/ml ::_10) at that time.
The GMT at 7/8 months for all vaccinees was 215.3 mIU/ml and 259.0 for
responders (mlU/ml ::_10).
Twenty-eight subjects have received two 10 mcg injections of vaccine , and 27
of these have received the third injection. One hundred percent (24/24) of
the participants seroconverted (S/N >_2.1) for anti-HBs at 7/8 months.
24£>41/10
00161
Studv 883 - Philadelphia. PA - Or. S. Plotkin and Dr. S. Starr (Cont.)

Ninety-six percent (23/24) developed protective levels of anti-HBs (mlU/ml
~10). The Gl'4T at 7/8 months for all vaccinees was 863.2 mIU/ml and 1084.9 for
responders (mIU/ml ~10).
There have been no reports of serious or alarming reactions to vaccine. The
Study 885 - Tampa, FL - Dr. A. Leibowitz

Initially seronegative healthy adults are receiving 10 mcg doses of vaccine at
0, 1, and 6 months from one of the following consistency lots: C-l215, C-L216,
C-l217, C-L219, C-l220.
One hundred fifty persons have received the first injection of vaccine. One
hundred of these participants have received the second injection. No
serologic results are currently available. There have been no reports of
serious or alarming adverse experiences attributable to vaccine. The study
Study 889 - St. Louis, MO - Dr. R. Perrillo
The study population consists of two in1tially seronegative groups:

institutionalized mentally retarded individuals and health care personnel.
Mentally retarded individuals receive either 10 mcg injections or 20 mcg
injections of vaccine. Health care personnel receive 10 mcg injections. All
participants are receiving vaccine from lot C-K937 at 0, 1, and 6 months.
Eighty-eight health care personnel have received the first injection of
vaccine and 82 of these have received the second injection. At one month, 17%
(14/82) of the participants seroconverted (S/N ~2.1) for anti-HBs with a GMT
for all vaccinees of 0.5 mIU/ml.
One female subject developed facial urticaria approximately one hour after
rece1v1ng the first injection of vaccine. All symptoms subsided within 12
hours after onset. The reaction was considered· probably related to vaccine.
The subject received Benadryl prior to the second and third injections and had
no post-vaccination reactions.
There were no serious adverse experiences attributable to vaccine. The study
Study 894 - Baltimore, MS - Dr. e. F. Polk

The study population consists of homosexual males who are negative for all
hepatitis e markers and have not previously received any hepatitis B vaccine.
Participants are randomized to receive either 20 mcg infections of
plasma-derived vaccine (lot C-M252) or 10 mcg injections of yeast recombinant
vaccine (lot C-K563) at 0, l, and 6 months.
24641/11
00162
Study 894 - Baltimore. MS - Or. B. F. Polk (Cont.)

Eighty-seven participants have received one 10 mcg injection of yeast
recombinant vaccine and sixty-three of these have received the second
injection. One subject only has received the third injection. Serologic data
are not presently available.
Eighty-eight participants have received one 20 mcg injection of plasma-derived
vaccine and seventy of these have received the second injection. Mone have
yet received the third injection. Serologic data are not presently available.
No serious or alaming adverse experiences attributable to vaccine have been
reported. The study continues in progress.
Study 898 - West Point. PA - Or. R. Bishop

Initially seronegattve healthy adults, 40 years of age or older, are receiving
either 10 mcg (1.0 ml) injections of vaccine lot C-M126 or 20 mcg (1.0 ml)
injections of vaccfoe lot C-F/1125. All injections are administered at 0, 1.
and 6 months.
To date, one participant has received the initial 10 mcg injection of vaccine,
while two subjects have received single 20 mcg injections of vaccine.
Post-vaccination serologic results are not presently available. No serious or
alarming adverse reactions attributable to vaccine have been reported. The
Study 900 - London. UK - Dr. A. Zuckenaan and Or. I. urray-Lyon

Initially seronegat1ve healthy male homosexuals are receiving 10 mcg (1.0 ml)
injections of vaccine lot c-~126 at 0, 1, and 6 months.
Serologic and clinical follow-up data are currently not available. No serious
or alarming adverse experiences attributable to vaccine have been reported.
Study 904 - Chicago, IL - Dr. H. A. Kessler

Initially seronegative healthy adults are scheduled to receive 10 mcg (0.5 ml)
injections of vaccine from lot c-~178 or from lot C-L217 at o. 1. and 6 months.
One hundred participants {50 for each lot) have received the first and second
injections of vaccine. Serologic and clinical follow-up data are not
presently available. No serious or alarming adverse experiences have been
24&41/12
Study 907 - Tokyo and Osaka , Japan - Dr. s. Iino and Or. T. Kuroki
Healthy adults are receiving 10 mcg (0.5 ml) intramuscular or subcutaneous
injections of vaccine lot C-L215 at 0, 1, and 6 months.
Sixty-two participants have received the first and second injections of
vaccine by the intramuscular route. Sixty-two subjects have also received the
first and second injections of vaccine by the subcutaneous route. One hundred
twenty-one of the participants (both routes) have received the third
injection. At one month after the third injection, 98% (54/55) of the
vaccinees who received intramuscular injections seroconverted for anti-HBs
(S/N ~2.1). Ninety-seven percent (56/58) of the participants who received
subcutaneous injections seroconverted for anti-HBs {S/N ~2.1) at that time.
There have been no reports of alarming or serious adverse reactions
attributable to vaccine. The frequency of systemic complaints was higher in
the subcutaneous injection group after the first injection and higher in the
intramuscular injection group after the second injection . The frequency of
injection site complaints are similar between both groups after the first and
second injections. The study continues in progress.
Study 912 - Japan - Dr. T. Shimizu , Dr.~. Nakao , Dr. T. Marimo. et al

Health care personnel are receiving 10 mcg (0.5 ml) intramuscular or
subcutaneous injections of vaccine lot C-L220 at 0, l, and 6 months.
Eighty-seven participants have received the first injection of vaccine by the
intra~uscular route. Eighty-five of these subjects received the second
injection . At one month after the second injection, 75% (56/75) of the
subjects seroconverted for anti-HBs {S/N ~2.1}.
Eighty-eight participants have received two injections of vaccine by the

subcutaneous route. At one month after the second injection, 59% (43/73) of
the subjects seroconverted for anti-HBs (S/N ~2.1).
There have been no reports of alarming or serious adverse experiences
attributable to vaccine. The frequencies of injection site and systemic
complaints, after the first and second injections, were high for vaccinees in
the subcutaneous injection group. The study continues in progress.
Study 914 - Bruxelles . Belgium - Or. A. Burette and Dr. M. Deltenre

Initially seronegative health care personnel are scheduled to receive 10 mcg
(1.0 ml) injections of vaccine lot C-Ml26 at 0, 1, and 6 months.
Twenty participants have received the first and second injections of vaccine.
Serologic and clinical follow-up data are currently not available. There have
been no reports of alarming or serious adverse experiences attributable to
24641/13
-·
PROGRA"1: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,
Study 779
PURPOSE: To evaluate antibody and c11nkal responses to the

vaccine among healthy adults who are negative for
hepatitis B virus serologic markers.

Lot 934/C-J62S (10 IIIC9 HBsAg/ml)
PRINCIPAL Robert P. Bishop, M.D.

SECONDARY E. P. Avancena, M.O.

INVESTIGATORS: Health Services
Merck Sharp and Oohme
Joseph C. Rogers, M.D.
Health Services
Joseph P. Romano, H.D.
Health Services
Rahway, NJ 07065
STUDY LOCATION: Merck Sharp and Dohme

DA TE CO~PLETEO: In progress
23901/1
l /2/86
001b5
Study 779
STUDY PROCEDURE: The study population consists of 41 healthy adults of

either sex (excluding pregnant women) employed at Merck
and Co., Inc., who were initially negative for HBsAg,
anti-HBc and ant1-HBs, had a normal ALT level and had
Eligible participants receive a 1.0 ml (10 mcg HBsAg)
intramuscular injection of var.rine nrnt111r~d by either
the immune affinity or the {b) (4) procedure at
0, l and 6 months. Study participants are asked to
talc.e and record their temperatures for five days after
each injection of vaccine and to record any local or
systemic complaints that they may experience.
participant approximately two weeks before
vaccination. Post-vaccination blood samples (10-15 ml)
are obtained monthly for seven months and at 9, 12 and
24 months following the first injection of vaccine.
Samples are assayed for HBsAg, anti-HBc, ant1-HBs and
ALT, and these may be assayed for antibody to antigens
in yeast extract. Samples w1th an anti-HBs titer >
25 mIU/ml units are tested to determine the relative
proportions of anti-! and anti-~ activity.
STUDY RESULTS: HEALTHY ADULTS vaccine):

10 mcg Lot 972/C-K444 at o. 1, and 6 months
Iniect1on No.
_l_ .......L. _3_
26 26 21
23901-2
1 /2/86
00166
Study 779
RESULTS (CONT.): 2. Serologic Results:

Sero logic data are available for 17 participants
at 7/8 months . Seroconversion (S/N ~2.1) for
anti-HBs at 7/8 months was 100% (17/17).
t.li nety-four percent ( 16/17} of the Vlltc i nees
~10) at that time. The GMT at 7/8 months for all
vaccinees was B08. 5 mIU/ml and 1124. 9 mIU/ml for
responders with a titer of mIU/ml ~10.
Among participants with serology data at 12
raonths, 100% (12/12) were positive for anti-HBs
(mIU/ml >10). The G~T at that time was 459.4
mIU/mi (all vacc1nees and responders by either
cutoff).
Refer to Table l for anti-HBs responses and GMTs
freQuencies of complaints are presented below.
Type of Frequency in% by Inject on No.

Complaint 1 2 3
Injection 23(6/26) 15(4/26) 10(2/20)

Site
Systemic 4(1/26) 15(4/26) 5(1/20)

There were no serious or alarndng reactions
23901/3
1/2/86
001b7
Study 179
RESULTS (CONT.): React1ons reported to the OoBRR

A 41-year old female subject, with a history of
multiple allergies, received her first and second
inject1ons of vaccine without clinical complaints.
Several hours after receiving her third injection of
vaccine, she developed a frontal headache and an
erythematous papular rash. One 4 mg chlortrimeton
tablet was administered. The headache resolved w1thin
24 hours and the rash faded over the next four days.
The clinical investigator considered the reaction to
be vaccine related.
PUBLICATIONS: Scolnick EM, Mclean AA, West DJ, Dienstag JL, Watkins
E, Deinhardt f. Antibody and cl1n1cal responses
among healthy adults to a hepatitis B vaccine made
by recombinant DNA. In: Vyas GN, 01enstag JL,
Hoffnagle JH, eds. Viral Hepatitis and Liver
Disease. Orlando: Grune and Stratton, 1984:
315-17.
scolnick E~. ~clean AA, West OJ, ~cAleer WJ, ~iller WJ,
Buynak EB. Clinical evaluation 1n healthy adults
of a hepatitis B vaccine made by recombinant DNA.
JAMA 1984; 251:2812-15.
23901/4
1 /2/86
Table 1
AHT1800T RESPONSES fOllOWIHG VACCIHATIOH WITH RECDtl:IIHAHT HEPATITIS B VACCINE

STtlDY I 0779
POPULATION I HEALTHY ADULTS
DOSE 10 11CG
LOT CK444
REGit1£N Ot 1, AND 6 ltOHlHS
IHITIAl SEROLOGY: HECATIVE
I Y. WITH ANTI-NBS I GHT INIU/Hll I

l---------------------------------------1-----------------------------------------------------f
I I I RESPOIIIIER!l I
Til1E
01011THSl
l---------------------------------------l-----------------1-----------------------------------I
I SIN>= 2.1 I HIU/tll >= 10 I ALL VACCINEES I SIN>= 2.1 I HJU/Hl >= 10 I
o••••••a••••••••••••••••••n•••••••••••••••••••••••••••••••••••••a•••••••••••••••••••••••••••••••••••••••••••••••••~
l '100TH t'9Y. (7/2" 17r. (4/24) 1.3 2,.0 99.7
2 NO!ITIIS 651. 115/231 52Y. 112/UI 10.4 59.4 110.4
l ttoHTHS 767. 116/Zll 62Y. 113/211 16.1 St.6 107.2
6 ttOIITIIS 897. 117/191 537. (10/191 19.3 ll.6 12t.6
719 MOtmtS 100% 1171171 MY. 116/171 909.5 909.S 1124. <J
9 MONTHS 1007. Ul/111 917. 110/111 767 .2 767.Z 127ff.3
lt Hlltl111S lODX (12/12) 1007. llUUI 459.ff 459.4 ff59.lt
.................................................................................................................. I
I
~
-
0
c,,.
0:,
Table 2
PATIENT COU4T ClJNICAL COHPLAJHTS
RECotflllHAHT HEPATITIS 9 YACCIHf
!!TUD'f I 0779
TlffATHENT
LOT NUHll[R CM'i4
oo,e JO m:&
IJtAT!fffT CLASS: Hl!ALT1fl ADULT!
I TOTAL VlCCJH£fS C !6 PATIENTS) - DOSE 1 I

, ______________ . -------------------------------------------------------------1
I DAU POST Yl CClNATlOM I NU18ER
CLINICAL
CCl1PLAINTS
l----------------------------------------------------------------------------1
I O f 1 I t I J I " f 5 D
MITH
IClltlPLAIHTS
a••~a•••••a•••••oa••••••••••••••••• l••••••••••l•••••••••••••••a•••aQl~•••••••••la••••••••• l•••••••tteala••••a••••loawna•waaw
I I f I I I f I
REACTION, LOCAL CINJECT. SITU I I
'i 1 I 1 I o I o I o I I 6
I , u.1i:o I , J.o;o I I J.ox, I , e.o:o I , o.o;o I , o.oY.1 I I , n.uo
-----------------------------------1----------l----------l----------f----------l----------f----------l----------l-----------
!!m!EHE!!S I ti I 1 I l I I I o I I f I 6
I C lS.47.) I ( J .8l!I I ( ll,8)!) I t o.o;o I I 0.07.1 I I o.o;o I I I U.17.1
-----------------------------------l----------l----------
s v91Entc I 1 I 1
l----------1
I o I----------l----------l----------l----------
o I o I I I l-----------
I 1
I f J.IIX) I I J.8?.I I I O.OlO I I I.OXI I I O.OlO I I I .Ol!I I I I J.87.1
I
~ E l!ODY/GEtfERAl I 1 I 1 I ti I O I t I O I I 1
I c , .a1. , I I J . 111. , I 1 0.01. , I 1 1 .01.1 I , 0.01. , I , 1 . oY.1 I I a 11.a:-: ,
I I D I I I I I
HEADACHE I 1 I 1 I ti I o I O I o I I 1
· I I J.11:1.) I I J.OY.) I I O.OlO I I o.o:o I I O.Ol'. I I C 1 .01.1 I I ( J.8)! )
-----------------------------------1----------I----------I---------- I---------- I----------I----------I---------- I-----------
PlRSOMS NITH Cot1PUJHTS I 5 I Z I 1 I O I O I O I I 7
I I 19.!Y.J I I 7.7Y.t I I J.OY.J I I 1. 0Y.I I I O.O?. J I I I .DY. I I I f Z6.9JO
-----------------------------------1----------1----------1
PfRSOHS wnH m cot1Pu1ms I n I tto I----------1
ts I
----------1----------1----------1
H I t6 I 1!6 I----------1
I
-----------
n
I I 80.8)!) I I 9Z.3?. ) I f 96.ZXJ I n oo.,x, I 1110 .0l! I I (100.0?.J I I f 73.lXI
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
PER!IONS MITH HO DATA I e I o I o I o I o I o I I o
I c 1.0:u I , 0 .0?.1 I c o.o:io I c ,. ox, I I o.o.o t c • ·'"' I I 1 0.117.1
-,,..
0
.0
Table 2 (Contd)
PATIENT COUNT CLINICAL CllttPLAINTS
R[CONIIItUNT HEPATITIS 9 VACCIN£
STIIUT 0779
lRUTNENT
LOT IM1MR CK<oll4'
DOS! I 10 ttC9
PATIENT CLASS1 HEALTHY ADULTS
I TOTAL VACCINE!S I 26 PATIENTS! - DOSE Z I

1I ---------------------------------------------------------------------------I
OATS POST VACCINATION I IM1MR
CLINICAL
CONPLAINTS
l-----------------•----------------------------------------------------------1
I I I l I Z I J I II I 5 I
WITH
ICCHPLAlNTS
•••••a•a••••••••••••••••••••••••e••l••••••••••••a••••••••l••••••••••l•••••••••• l•••a•••••• l•a•a•~••••la•••••~a•• I••••••••••
I I I . I I I I I
REACTION, LOCAL I INJECT . SITE I I I I t I J I 2 I 1 I I I I II
I , J.a::o I 1 1.n1 I r n.n, I , 1.no I , ,.a::o I c o.ou I I c 1S .11Y.1
-----------------------------------1----------l----------l----------l----------1----------l----------1
SOIIENE!IS I 1 I t I I I I I O I 8 I
----------1-----------
I Z
I ( J.87.1 I I B.IY.I I I 3.8Y.) I I 0.0lO I l 0.0)() I I 0.01.J I I C 1.7)0
I I I I I I I I
TIEIIDERNES9 I o I l I I I 1 I o I • I I l
I I O.OiO I C J.8l0 I I J.8i0 I I J .8)0 I I , .o;o I I 0 .07. 1 I I I J.8i0
I I I I I I I I
9TtffN£99/TI6ffTHES9 I o I l I l I l I 1 I I I I 1
I 1 0.01.1 I c J.e:o I r ,.a:o I I J . a 1.1 I I J.e:o I c 0 . 1:0 I I , J.&Y. I
-----------------------------------l----------l----------l---------·1·---------1----------l----------l----------l-----------
9TSTIEHic I o I J I • I 1 I J I J I I 11
I I 0.01.1 I f 1 1.SiO I I 0.0Y.I I G J .l!Y.I I I 11 .SY.I I I 11 .s:o I I I H . 11?.I
eMOLE 80DT/6ENERAl I 0 z It l l 0 J
I.OlO C 7.7Y.I I 0.01., C J .87.t I J .87.t I e.e:o I 11.SY.I
SWUTIK&
I
0
O.OY.I I
l
:s.e:o I "
0.01.t I
0
0.0)() I
0
o.o:o ( •.0,.r., (
l
3.11.J
SENSATIOH OI' NARHTih CENERAl

I •
• . ,:o I
1
J.OY.J I
0
0 .0)0 (
0
0 .07.J I
0
0 .07.1 I •
0 . 0:0 (
l
JI . BY.I
HEAOACNI! 0 I Cl 1 1 0 2
o.o:o I J.lliO 1.0:0 I J .IIY.) C J.81.1 I 7.7)(1
RUPJRATORT
' 0 0
' 0 D 1
O.IIY.J
1
I
·1
I 1.0)( 1
• I .DY. I
' 1 . 11.1 ( I. DY. I
• J.e:o ( J .eu ( :J.a:o
PHARlHGtTlS I SO'Jt! ntROATt
I
0
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•
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o.o,o ( O.OlO
• I
0
0 .1)0
•
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•
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J.111.1 I
1
J . IIY.I
0
J
CARDIOVASCULAR I
I I
0
I . OY.t I •
I . ll! I I •
1 .01. 1 I
I
J . 11)!1 I
l
J . IIY.I
•
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3.IIY.I I
1
J.Ol!I -
0
....,
0
Table 2 (Contd)
PATIEHf CCUfT CLINICAL ClltV'UJ NTS
RECor181NANT HEPATI TIS B VACC I NE
STUDT I 0779
TREATnENT I
LOT ..mBER I CK444
DOU I 10 tlCII
PATIENT CLASS • HE AllffY ADULTS
I TOTAL VACCIH£ES t 26 PATIENTS I - DOSE 2 •

1---------------------------------------------------------------------------I
I GAYS POST VACC I NATJOff I IUtlER
CLINICAL
tOltPlAIHf9
1------------------------------------------·---------------------------------I
I o I 1 • 2 I :, • , I s •
MITH
•cot1PLAINTS
••• • •••••••••••••••
8
••••••••••••H•l•••••••••••••••••••••••••••••••••••••••••••l•••••••••• l••••..•••••••••-••••lat1••••••••
• • I I I I • I
HYPERHNSJOH I O I I I II I 1 I l I 1 • I 1
I I o.o:o I ( •. ,x, I I , .o:o I t J.8?.I I I 1.87.1 I t J .81. 1 I I t J .eY. I
I I I I I I I •
DI GESTlYE STSTE" I O I l I O • I I l I 1 I I t
I I o.o:n I c 1. e;-., I 1 0.0;-. 1 I I e.o:o • 1 1. e;-. 1 I 1 1. e:n I I c 1.r,o
I I I I • I I I
NAU!EA I o I l I o I • I l I 1 I I 2
I I o. ox, I , :s.ez , • 1 o. oz , • c e.01. , I c 1.e:o I , 1.e1. 1 I I c 1. r,o
-----------------------------------
l'tRSOH! Wlffl Cllffl'LAIIITS
•----------
I l I•----------1----------l----------•----------1----------1----------1-----------
I I J I l I 4 I J I I a
I 1 :,.ex, I c n.z7. t I 1 11 .s1. 1 I , 11 . si , I , 15 . 47.1 I , u . 57. t I • 1 J0. 8 7.t
-----------------------------------1
PERSOM WITH NO CCIHPLAltffS I ----------•----------l----------1·····-----•----------l----------l----------•-----------
ZS I 21 I rJ I U I 12 I U • • 18
I I 96.2)! 1 I I 81 . 87.t I I 98 . 57. 1 I I ea.s:o I I M.6:1'.I I I 18.Sl! I • I I 69. ZY.I
----------------------------------- It----------l----------l----------l----------l----------1----------1
PPSfflft MITH NO DATA O f t I e I O I t I e I ----------1
I -----------
e
• I 0 .0)! ) • I G. llO • I t . l Y. 1 f I , .e:o I I I .OXI • I • •• ,o I • I 0 . 0)!1
--
0
~
Table 2 (Contd)
PATI(NT COUNT CLI NICAL COffl'LAINTS
RECotlllINANT H£PATITIS ~ VACCINt
9TUIJ'f 0779
l RE ATt1EffT
Lor NUtfflER I CK41tlt
009! 10 HCG
PATIENT CLASS• MEALTM'f ADUlTS
• TOTAL VACCJNE£ 9 I 21 PATUNTS I • DOSI! l I

•----------------------------------------------------------------------------1
• OA'fS POST VAtCI NATJOff I IM1'8ER
CLI NICAL
COl1P LAI NTS
•----------------------------------------------------------------------------1
I O • 1 I t • l I 'I I 5 •
MITff
•c0t1PU INTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•••••••o•• l••••••••••I••••••••••
I • I I I I I •
REACTIDH, LOCAL IJNJECT, SITU • t • t I O I O I O I O • • t
• I 10.0Y.I I I 10,0l!I I I t .07. 1 I I o.o;o I I O.OY.I I I O, OY. I • I I 10. 0i': I
----------------------------------- l---------- l----------l---------- l----------l----------l----------l----------l-----------
90!!£Nns I t • t • o • o I o I o I I t
I 1 10 .oin I , 10.o;r. 1 • c , . ox, I , , .o;i1 I , o.e::o I 1 o.o,o I I , H . or.1
----------------------------------- Il----------
s r s nn1c 1
l----------
I 1
l----------l----------l----------l----------l----------l-----------
I I I I I I I t I I 1
I I 1.0:0 I I 1.1?., I I 5 .0Y.t I I 5 .0?.I I I 1 .07.J I I o.o,o I I I 1 . 0:0
~OLE BOO'f/GENERAL 1 1 0 0 0 I 0 1
• 5 , 0?.I 5 . 17. ) I o .o:o 0.1::0 t .o::o I c t .01.1 5 . l l!I
[OEttA, fllCE I 0
' 1 0
' •
' 8
I
I 0 1
O.DlO 1 , 17.1 I 0 .0?.I t .OlO 0.07.I I I 5 . t Y.I
' ' • ' • I
O.llO
•
O. •
ffEAOACHE I 0 I
1
I t ?. I I ,.o,o 0 .0,:1 I 1 O.H I
l
5. t iO
5. 01.1
'
t .OY. I
'
INTEc.tnNTARf STSTE"
PRIJRI Tl S I ITClt I N&

.' '
I
I
o
O.OlO
0
'
1
5 .tl!I
1
I
•
1
s.oz,
' '
l
5 .tY.I
1
5,tlO I I , . 0,:1
l
5 .0)! J
1
0 .0)0 5 .07.1
' ' I' '
0 . 0,: 1 1 .07.) I .DY.I I I 0 . 1 7.1
( I 5 . 0i': I
ltA91t, NM I t I l I l I l I l I 9 I I l
I I 0 . 01. , I I 5 .0)0 I I 5 .lr,O I I 5 .0?.t I I 5.07.1 I I t .!IT.I I I I 5 .0iO
-----------------------------------1
PHSOHS eu nt CottPLAINTs •
----------t----------1
! I 1 I
----------t----------1----------•----------1----------•-----------
1 • 1 I 1 I , I • ,
• C H,OlO I C 15. 07.1 • I 5.0Y.t I I 5 ,07.1 I I 5 .0Y.I I I I . OY. I I • C 15. 0¥- 1
-----------------------------------f----------
n11scms &in H HO cONPLAI NTs • 11
l----------l----------
• 11 I 19
t----------l----------l----------l
I n I 19 I H I
----------l-----------
I 11
• , e s .ox1 I I a s .o;r.1 I I u . o:o I f ff.ox, I , n.ox1 I uoo.1x 1 I I , H .o?. 1 0
-----------------------------------•----------•----------1---------- •----------l----------1
I ----------1----------1
I -----------
PU!ffllf'J &!I TH NO DATA I
I I
l I 1 •
~ .s x , I I
1 I 1
4 .&Y., I I
I l 1
1) . 8?. l O I
I
4 . &Y.I I I
1
~ .8l!I I C 4 . 8l! I I I I 4 . 8 ?. • -"
0
1\1
Table 3
PATll'NT COUNT "AXnut Ttl1PERA~E9
RECOl181NAHT HEPATITIS 8 VACCIN!
STUDY 0711
TREATttEKT · 1
LOT tMfflER t Cl<'144
9~E I lO tc9
PATIENT CLAS9t HEALTHY AIIVLTS
I TOTAL VACCIN£1ES I Z6 PATllNTS J • OOSE 1 I

l--------------------------------------------------------------------------------------1
I OAYS POST VACCINATION I NUHIIER
nax TEl'IP£RATURE
IOEG IF, o,iau
1 ---------------------------------------------------------------------------------------I
I o I 1 I t • J I <1 I s I I I ""xMI nnP
TH
aaa•••••••••••••••••..•••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••--••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
NOlfNIIL I 1 I 1 I 1 I 1 I 1 I 1 I • I
IC J.a,o IC J . IIY. I II 3.87.t If 4.f1.I I( 4 .t:JO II 4 .JY.I I II J .e,o
I I I I • I I I
< n I 24 I 24 I t4 I n I rt I n I I n
I , 9t.J1.J I c n.1;O I I u.J?.t I 1 95.eiii I t ,1. r1., I , n.Jl!I I I t eo.111.,
I I I I I I I I
99 - 99. 9 I 1 I 1 I l I o I l I l I I ~
I c 1.111.1 I c J.eio I I J.eio I 1 0.01.1 I 1 4 .t,o I t 4 .J:o I I , 1s.41.t
------------------------ Il----------
nr,pp11TU111! TAKEN H
l----------l----------l----------l----------1--·····•--
I u I H I t4 I 24 I n
l---------------------l-----------
I I H
I uoo. er. t I uoo.e;o I llH.0Y.I I t 92.J)!t I I •t.V.I I I aa.sr., I I U00.07.1
------------------------l----------l----------l----------l----------l----------l----------l---------------------l-----------
nnP£RArutrE KOT TAKEN I o I • I • I 2 I 2 I J I I •
I C o.or., I C 0.17.1 I t o.o;o I I 1.TI.J I I 1.r1., I t 11.sr., I I I 0,07.1
.....,=»
v,!
Table 3 (Contd)
PATIENT mMT tlAXINUH TEl1PERATURE9
IECOtlBINANT HEPATI TIS 9 VACCINE
STUDY : 0 779
TIIUTI1ENT :
LOT HUtfllEII I CK•44.>
DOSE 10 t'ICG
PATIENT CLASS: HEALTHY AIIUt.T9
I · TOTAL VACCINEH C 26 PATHHTSI • DOSE 2 I

1···········-···-·····-···-·--·-···--·--········-··-·······--········-·················-1
I DAYS POST VACCI HATJ«m I NUr!BEII
HA)( TElftAATUllE
l DEG I', OltAll
1
I
•······•·•··········•·••··•••••····•······•·-·····•····•·•···························••1
e I 1 I t I S I 4 I 5 I I
NJ TH
I NA)( TEffll
••••••••••••••••••••1tt1-l••••••••••I•••••••••••••••••••••••..••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
NORHAl I t I t I t I t I t I t I I t
e.o,o I c I C e.o:r. t I c 8. 7:r. l
8 . Cl:r. l I I a. r,: 1 I 1 , .uo I I I 8 . 0lO
II ' I I I I I I
< •• I H ' I 2G I u I t1
88. 0XI I I H . t :r. l I I 92 . 0Y. I I C 91 .3:'- I
I u
I C 91.31.I
I rt
I I 90 .9"/. I
I
I
I 19
I c 76 . o,o
I I I I I I I
99 •
" ·' I l I r I 0 I
4 . 07. 1 I I a.11;O I I 0.0:r. 1 I c 0.0lO
·o I
I I
0 I •
0. 0:r. 1 I I 0 . 0l'-1
I
I
I 3
I I lt.0lO
101 · lDl . 9 I o I 1 I o I o I e I o • I l
I I t.0lO I C 4 . t Y.I I I a.o,o I I I . 0l'!I I I I .0Y.I I I 0 . DY. I I I I 4.0l! I
··--·-·-----··-------··-1I -·····--·-1
TE11PERAT\JRE TIU(EN zs I
·--·-·-·-·1·---------l----·-····1-·------·1-----··---
ts I ts I ts I 11 I 2t
l---··--·--··-······-·1I ·-·-··--··-
I ts
I C 96.t:Y. I I C '6 .ti'.I I I 96 , 27. 1 I I ea .s:o I I 88 . 51. 1 I I 84.61. 1 I I I '6 . 17.1
----------·-···-········1···--·····1-·····--··1
TEttPERAT\JRE ta>T TAkEM I 1 I 1 I
·····--···1
1 I
········-~l---·---···l·-···-----1
J I J I • I
-------··--·--······ Il·-·····-···
l
I I J.8Y. I I I J . 17.1 I I J,8Y. I I I U . 57. 1 I I 11 . s :r.1 I I 11 . 4 %1 I I I Jl . 8 Y. I
-""'
0
0
,:::
Table 3 (Contd)
PATIENT COIMT 11.um u, TEIIPERATURES
ltECOHBINAlfT HE PATIT IS B VACCINE
STUDT I 0779
1A(AT'1lNT
LOT IUTB(R : Clt444
00!11: r 10 m:&
PATIENT CLAS9: HEALTHY ADULTS
U TOTAL VACCINEES C t1 PAllENTS I - DOSE lJ I

1-·--------------·-----·-··-----.-·--·-·-·-·-·-··-----··--·--··--------------·--·------·I
I DAYSI POST VACCIHATIDN I HUffllElt
"AX TEHPERATUSIE
IOEG F • 03fAL I
1-·---·----------------··--·---------------------·----·-------------------------------·-
I O I 1 I 2 I J ·I 4 I S I I
I 141 TH
I HA)( TEMP
oo•••o••••••o•••••••••••l•••••••••al•••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••a• l•~••••••••I••••••••••
I I I I I I I I
tmt1Al I s I s I s I 5 I 5 I s I I S
I t H.OY.I I I H.1:0 I G H .• OY.I I l t7.81.I I C H.4Y.I I C !7;8)0 I I I H.Di!I
I I I I I I I I
< 99 I 14 I lit I u I u I u I n I I 14
I I 70. 0l!I I C 70. l lO I l 71.0:0 I l •6.7ll I l 10.•Y.I I l 72.ZY.I I I I 71. 0X I
I I I I I I I I
99 · 99., I 1 I 1 I o I 1 I o I o I I 1
I l s.o:o I C s . 01.1 I I O.OY.I I c 5 .6'0 I C 0.01.1 I c o.o:o I I I s.11.1
---------··---··---··-··1··--··-·-·1
TEffl'tAATUl!IE TAKEN I 21 I
--····-·-·1--·-····•-l••--····-·1····-·---•l--··-·····1·······-·············1-····-·····
20 I !O I le I 17 I 18 I I ti
I c ,s.21.1 I t 9S.t1.1 I , u.u:, I c n. 1io I c 1n .1i-.1 I , es. 1.0 I I 1 95.z:o
··-·····················1-·····-···1
TEffl'ERATURr oeor TAltltto 1 1 1
······--·-1
1 I
··········1··-·······1
1 I 1 I
·-···-·-··1
'+ I
···-------l-·---·-·-····-·-··---1···---·····
J I I :a
I C 4 . 8 Y.) I I "·8)!) I I 4 . a ;,o I I 14 . ] )0 I I 19.0lO I I l<\ .])! I I I I 4.11:0
-...,
Q
\/1
00176
Edward M. Scolnick. Arlene A. Mclean.

David J. West. Jules L. Dienstag.
23
Antibody and Clinicml Responsf:s Among He11lthy
Recombinant DNA
Cumntly, all commercial hepatitis B vaccines are comprised of HBsAg purified

from the plasma of human carriers of the virus. However, the use of recombinant
DNA technology to effect synthesis of surface antiaen by a culture of microorgan-
isms is an attractive alternative to infected human plasma as a source of HBsAg
for vaccine. Good e>.p~ssion of the enc for HBsAg has been effected in yeast
(1).
Recently, antiaen purified from fermentation cultures ofa recombinant strain
of the yeast. Saccharomycts cerevisiae containing the 1ene for the adw subtype
of HBsAg was formulared into a vaccine through abM>rption on alum adjuvant.
Two methods were utilized for the purification of the HBsAa. Immune affinity
chromatography uses specific an1i1en-antibody bindina to effect purification, while
the second method, hydrophobic interaction chromatOll"lphY followed by 4el
exclusion chrom&tOITlphy, depends upon the selection of water-immiscible mol-
The physical And chemical characteristics of vaccine made from HBsAa pro-
duced in yeast are very similar to those or vaccine prepared with HBsAg purified
from huffllln plllSfflfl. Funhermore, the yeast recombinant hepatitis B vaccine has
been shown to be both immuno,enic and protective in animals (1).
We repon here the clinical and antibody responses obtained in the first three
human clinical studies of the yeast rccombinan1 v&cc:ine involvin1 a to1al of 101
VIRAL HEPATITIS , net LIVER DISEASE Copyright e 1184 by Gn.mm • Stnmon

ISBN 0-&089-187M All righls of 19p,oduc:lion ii\ •nv form ~ -
Stoln1ck E~. tl n M. st DJ. 01 ftit t Jlo tk1ns E. O~inh n:at f.

Ant1b~y nd c11nicQ1 r spons s ft~ h lthy t dulti to h pat1t1! D
~ ec1ng ~ ~~ c 1n~nt DNA. In: V~ ~ , Di nst~~ JL. Noofn gl~ JM,
edi. ~ir 1 Na~ t1t1~ nd Li~ r Dis s. Orl ftdo:GFl!n nd Str tton. 198~:
31s-n.
00177
316 Scolnidt, McLean, Wea\, e\ al
vaccinees. Participants were healthy, nonpregnant, adult volunceers. At entry,

subjects were neptive for all hepatitis B seroloric markers, had a normal ALT
level, and had not received any other hepatitis B vaccine.
Panicipants in the studies received I .~ml intramuscular iajection or the
yeast recombinant hepatitis vaccine containing 10 ...a of HBsA1 t O, I and 6
months. The V2.Ceine used was from one of two lots. (Lot 93'4 prepared by the
immune affinity chromato,raphy method gnd Lot 972 prepared by the hydrophobic
interaction chromatography method.) Veccinees were asked to record their tem-
perature daily for .S days after each i!\iection of vaccine and to rei,ort any local or
systemic reactions that occuncd durina that period.
Postvaccinaition blood samples were taken for the determination of hepatitis
B seroloJic markers and ALT. ln llddilion, radioimmunoassay for the detection
of antibody to utiaens in an · elttnct of yeast lacking the 1ene for HBsA1 was
gpplied to pre• and postvac:cination samples.
The vzcc:ine was well tolerated. There have been no serious adverse effects
ttn'butable to vaccine and no evidence of hepatitis B infection amon1 the vaccinees
(i.e., no elevation of ALT m.nd no antigenemia). Loc&l reactions coasistina prin-
cipally of miJd sorcn~ss ar lhe uucction site, generally lastin1 J-2 days, have been
reported followin1 ~ of iqjections with vacc:inc purified by the immune
affinity ehromatop-aphy method (Lot 934) and I6~259' of injections with vaccine
purified by lhe hydrophobic interaclion chromatc,erapby method. Systemic com-
plaints includina f: tigue, headache, elevated temperature (101• f-102" F, oral),
pstrointestinal disturbance. symptoms of upper respinitory infection and nose-
bleed have been reponed Collowina 4~339'ofinjections (Table 23.1). There have
been no significant increases in antibody to antiaens in yeast extract associated
wilh vaccination.
Table l3.I
Cliniclll Responses among Heillthy Adults to 10 t't! Doses of
Rec:ombinant Hepaititis B Vaccine Administered at O. 1 and 6
Months
Proponion (Cji) orVaccinee1 with Oinical Complzints
within S Dllys or Vaccination
Study t1 VeccineLot Site I>osc I ('Ji) Dose?(~) Dose 3 (~)
779 934 Lc=I 12/15 (IO) 11/ISm) II/IS (73)
Systemic 5/15 (33) 3/IS (20) I/IS (7)
m Local 6/24(25) 3/19 (16)
Systemic 1/24 (4) 3119 (16)
934 ~ 19/28 (61) 11/21 (39)
Systemic 5/2101) 4r.8 (14)
79S 934 Local 51?5 (20) 6/19 (32)
Systemic 51?5 (20) 1/19 (5)
00178
HBV Vucc:infl Mede by Recombinant ONA 317
Teble 23.l
Sen,c;onvenioa Frcqucnan for Anti-HBs among Healthy Adulu
Receiving 10 ...a Doses or Recombinmnt Hepatitis B Vaccine at O, l
1111d 6Months
Proponion (9i) of Vaccinees with Antibody
Study Ill Vaccine Lot '1 !Mo. 2Mo. 3Mo. 6Mo. 7Mo.
ffl 9~ 6/15
(40)
'"l.S
(93)
l.S/lS
(100)
15/IS
(100)
U/14
(100)
m 7/24 13/19 12/14
{29) (61) (16)
792 9)4 11/ZI 21/23 ll/13
(39) (91) (ICIO)
934 l/30 21/30 19122
(27) (70) (86)
Antibody responses to 10 t1,g doses of

the yeast m:ombinant vaccine have
been compgnible to tho1e observed in previous studies with 20.,,.. doses of vaccine
prepared from plasma-derived HBsAg. At I month, 2 ~ or the vaccinees
were positive for Mti-HBs. By 2 months, 68%-939r, o( the vaccinees had anti•
HBs, and ac 3 months 869'-IOOCJ'o were anu"'body positive (Table 23.2). The third
dose of vaccine at 6 months has been &iven to U persons in one of the studies,
rcsultin1 in a mon: then 2'-fold increase in eometric mean liter.
REFERENCES
I. Valenzueln P, Medioo A, Rutter WJ, et &ll. Synthesis and usembly of hepatitis B vitwl
surfa1ce an~n panic:lcs in yeast. Narure 1912; 291:3'7-3,0.
2. McAleer WJ, Bu)'llak EB, Mminener lZ, et lll. HumM hepatitis B vaccine from
n:combwlftt )'alll. Nature 1984; J07:17B-IIO.
,.,,__,,.,,,,_,,_.,11:)_ldcdlaJI__.
....., , . 1134. _a,
' - " " ' , ~. - llo<l/t;d ~
Original Contributio ns
Clinical .Evaluation in Healthy Adults of a

Hepatitis 8 Vaccine Made by Recombinant DNA
Edward M. Scolnick. MO; AMnG A. t.AeLHn, PhD; David J. West, PhD; Willitlm J. McAlceQr, PhD;
WLlliem J. Mil!Qr, MS; Eugene B. Buynak, PhO .
• A vecclne formulrited from hep8tltlo I eurfac ntlgen (H88Ag) Since there ii no ·elrtctive treat-
produced by c recombln nt 1traln of the y eat Saeeh romyeeo ee,ev/.,11 me nt ror hepatitis B infection, pre-
wae 11dmlnl1ter ed to two 9roupe of human volunt r11 compoeod ol 37 vention in eaential. A safe, effective
he11lthy, low•rlGk lldUltCI. Emch I Ubfc)cl rocolved I 11>,19 dOIS of HBsA9 et o. 1, human hepatitis B .ac:ciae is now
a nd 8 month • By onti month, 27% to ~ of tMJ Y ccln && had enUbody to nilnble. However, it utili1111 hepati-
HB111A9, nd by Ulree montflfl 101' to 10041(, w r 11ntlbody poeiUH. l roe> tis B 11unacs antigen (HBsAg) puri-
boo1t11 In ute, fOllowed t tM> third doM at 1 111 monthe. TII enUbody fo,med le fied from the pluma of humu cal't'i-
preoomlnainUy t1p1cmc fo, the • determln11n1 ol HBut.9. There tltlv b n 1110 .ers of hepatitis B rirus infection.
aerloue r11actlon11 11ttrtbut&!bkD to the YIICCln • Th fflOflt r, qu nt complelnt Coaeeq11111t1:r, the suppl)' of vaccine is
h111 be n trenalent 1orene I at th Injection 11ft • Ae fer llfl w know, lhkl Is potentially limited by available
th flrat r ported UH> In m n of II w11ccln1> prepl!lred by r ecombinant DNA aourcec of suitable plasma. In addi-
technolo9y. tion, extensive processin1 and safety
(JA MA 1fHM;2S 1:2812•2815) tettin1118v been neceaary to ensure
production of a vaccine a11ti1en that
i1 pun aad free of any extraneous
WORLDWIDE, human hepotiti11 B chronic carrieni now atimnted to living agent that might have ~n
infection constitutell II major public n,unber aiore than 200 million! laftc• present in the startin1 plumL Even
ht11lth problem. la addition to the t.ion ia tranamitted to su■ce ptible pear• thoqh multiple iAactivation treat•
disability auociated wit.h acute dilli- ·· son11 throu1h cont.llct with t.he blood, ments used in the ant.i1en p,nifica•
cal diuue, chronic liver di1&111e1, cir- semen. or w i'nl of chronic curien or tion proceas hue • n 1hown to inac-
r hosi11, aiad primuy hepo&octlllular persona euf'leriAs acute in!ecUon. In tivate representatives of all major
carcinoma are now ~ MqUe- low-incidenCi countrieo, 1uch u the BfOUpEI of animal ~ruaa: concern
1 e of UJU'tiOlffll hopmtitia B ill- United St.A th rink of h• titin B over the theoretical poaibility oC a
infection is still high ambDf curtain living orp.aism such u the etioloric
$ lao p 2785. groups of htalth CIINI personnel, agent of acquired immune deficiency
1)£tienta receiving dialysis treatments syndrome being present in pluma
fection. Indeed, m eome U1llUJ of or blood product8 made from large 11nd surviri"I the purification and
Asia and aub-Su&ru Africa, pri- pools, children born to AIAslui.11 E.slci- inactivation procedures has slo11,ed
mary hepatocellul r ciircinoma ootcln• moa or to lndochine~ or Haiw.n uceptance of hepatitis B vaccine.
sibly attributable to hep titis B inft c• refugees, res idents of institutions for A promising a lterna tive to infect~
lion ranks s n lendin CAUSG? of the mentally hnndicnppcad, pr iaoners, human plasma u a source o{ HBsAg
cancer deoth11 among mr.lw.' usera o( illicit injec:tnbhi drug11, and fo r vaccine i1 the uae of recombinant
The reaervoir or hepatiti B viruo persons ho nr<1 &Gmolly very pro- DNA technolc,ey to effect synthesis or
,...,,. ...,-
resides moinly in a popufotion of
"°"""""'·Mc,eb"""'"
.'11081~.Po.
11-,,d IOIOMo,cl, ~,-_
taelllooco,ct>,Mc;,c!iS!lo,pll~IICQCOICfl
miseuo1111.' In high•incidenCQ 11reas
ouch o, SoutJumct A.ail\, truGmioaion
from mother to child in the perinatal
p12riod is the mnjor mod!il of in!ection
oupplemented by horizont.!l tr ns•
mi111io11 batwoon othar family con•
the aurf~ ntigen by a culture or
microd?g niamc. The hep:atitis B vi-
rus gene codin1 for HBsAg has been
cloned both in E,c~hio. coli and in
y,eut ..'; however, expression oC the
aene in yeast has been much better
La--.00. "1D81 11:nt. PA I 11):1 ~ . t.acLa.' thr.11 in £ coli. Furthermore, HB!Ag
Hopolilill II Vecc:inc-Scotn,cll Ill 81
00180
produced by r•combinant yeast ~lle eonseat was oblllined after providing e.nch mllliunita per milliliter 11sinc the fonn11la•
has bc!en shoW11 to nrgregate into partieipll.Dt ..;th ialor11U1tio11 oa tho 1011reo tion dt111:ribed by Rollit1ger et aL" A
particlH clo1ely resemblintr thoae i110- of the i.avestigational yaut rec:Gmbinn.nt 111rum 1Amplt •aa i:oasidtred positive !or
l1.ted from human pluma. and this hepatitis B •accine, nuimal tfl11t results aa.ti-HBa if the ratio or the 1&mple co11nts
material was 1hown to include anti• obtained with the nttine, •acciaatioa and per minute to the 11eptin control serum
bleeding lclledulu, Uld the potential risks cocu1t1 per miaate vu 2..1 or gTeater.
bodies in mice and guinu. pigs..u and bznellts of participation in tho study. Eltimates of the proportioo or aati-HBI
Recently, anti,en pari.fied from fer• in poatncclnatioa sera specific ror tbe o
mentation c:ultures of recombinant Vaccln or a dewrminucs o! HBsAg wen band on
strain of the yeast SaccAaromrea an uaay deecribed by Hoofnacl• et al."
Hepatitis B sunace utipn for the
Uff'flinu containing the gene for Britll)', a liquot& of eac!i seNm sample are
•acciao was prodllClld in f11n11u1aLluio11 cal-
H~aAg has been formulated into n tul'ell of a rta1111biai111t strain ol th• J'81)8t ine11batod with II nbt>,,e od HB,Ar·
T&ccine through adsorption on alum S cerffiliGo coatai11i11t1 a plu111id CIIITY\III! poaiti•e .wrwn, with• subt'yl)e 011 HB1Ae-
adjuvant. Electron microtlCOpy re- the 1-■1 for the ollv, 111btype oC H&Ag. as po■itive aenun, a nd lrith normal bumaa
vu.11 that the purified H&Ag used lllncribad P~F-u:i mrum for two houn at room temperature,
Cor this nee.int ui1ts u agrepte Two methods '5111'11 1mploysd for tho a nd I.hon each aurtun ia carriad through a
Fillcatio11 · of HBaAg. 1-UAII aJ&aity lltandant radioimm1111oauay to m1u11ri
partidea 20 to 22 nm in diameter, a
chromato,raphy ues apecific t.11tigea- nsidwil aati-HBa.. Baa.d oa the perc:ut o!
morphotoa also elulracteri1tie of !RE neutraliutioa with tbli two HBsAr 1ub-
aurlace antipn in ilLflet.t pwma utiboclr biDdiacr t.o dact purilcatioa.
vbile the -.and mauiod. hfdropliohic tJ'llG aeni when c:ompured with the llllllft•
and o( the purified antipn aow uBGd traliud nonnal ballWI 111n1111, ao fttimate
iataractioD dlromatol!r&Phr followed .,,.
in plasma-derived hepatitis B fl\Ceiu. pl adusioa ehroma.t.DCnpbJ, ilepeadl oa can be made of thv relali•e &alOIIIICI of
In contrast to HBsAg Crom bu.ma.a aalec&icia of water-immilcillle mokcweo anti-c1 and anti-ii antibodi• pr...111. SiDce
pluma, the antilen produced by followed by aepsratio■ br 111ollealar ma. the nc:ciu ii a mono•alont•l)'pe ldw
rec:ombiunt yeast is not s l:,a,11- Detaila of the upreuiaa ol HBaA.g ia preparation, IOl'II ril coaiaia either aati•d
lated. U11der reducing eondition1, IO- ,-at and tJie puriAcatioo el cllo olllfMU antillodies, uti-o aatl11odias, or II combi-
dium dod~l sullaui 1l11:trophornisJ utipo will bo published olaevure.. Puri• A&tion ol both tn,a. ud th, amount oC
oC the antigen purified from yeut hd ffBaAs WU ttulad with fonnalclo- Dttutralisatioo widi the HBaA.1-or tor11m
byde t.o lt&biliu tJie material wt to kill la therefore & cliHCt auay (or the amocmt
reveals single band of molscular or uti-c pra1nL S11btraeti11g the amoaat
weight 23,000, which eorresponcla to 1111 utr&IIIOUI li¥ing Al3dUl that might
the non,tycosylatal polypeptide that be pnMllt. The aatipa wan Ulen formu• . or owtraliu.tioa with the HBIA1-or
lat-' imto • .-.cciao through adtorptioo OD aorum from that f011Dd for the HBsA.1-Gd
is the major component of th bepti- al11111 MlJavut t.o sl"' 10 114 ot K'BeA1 ud actrum thu si""1 u 11timat1 of the
tis B ril'UI envelope. The Taecine 0.5 1111 of alunlinara (bydrollide) ptr 1·&1. IIIIIOllllt or and◄ prtMDL
formulated using this material bas dote. TIie !aal lonaulation alao c:oatained A radioimmuaousay wu de~elol)ld to
now been shown co ho immunogenic 1:20,000 thi111ero&al u a pl'OIQrY&titc1. VIC• doted ,east antibodies ia tht 1era o(
for mice a nd for monkeys with a CiDI WU maiutained at z to I·c aatil .-ueiae neipielita. For this usay, u
•nnet of the parent atrain or S ~
potency equal to or superior t.o of mat l&IOd.
lac:kina the plumid coatalaiac the pne
vaccine made Crom plasma-derived
Procedurec for KBaA1 wu prepared by di1r11pti111 a
antiaen. la addition, chimpanzees im• 501o 1U1peasion o{ the cella in a hom01e-
munized 'With this ;yeast recombinant A blood u mpli wu obc&illGd fl'OII\ acli 11W1r aad then clarilictd by eeatriluption
hepatitis B Taccine (HBaA1 aubtype a11bject app,ocimaietr two WNIUi prior to at 9,000 r followed br puaaa, thrD11ch a
adio) weN! fully protected when chal- the lrsl 'IMCiu\ioa aad wu \e&\ed for 0.45-ni,.m membraM 6.lter. The clari.&ed,
leneecf with rirus of either type ollr or HBaA.1, antibody t.o H&Aa (aati-H&). filteNld estnct wu diluted t.o a linal
avic, •·bile an.immunized animala all utiboclr to c:on antipa (aati-Hle), nJa. protein coacentratioa of 80111/rnL wii.h 0.1
aiH amiaouulforua (A.LT), and yeut M carbociate buffer uul pH 9.6 and
show.d evideoce of ilLfectioll whea
utibocl,. Sobjecta louad lisible oa th0 adsorbed to \! •in pol)'ltyrene beads over•
c:halleapci.•
111 this article we describe NlllWtll of
buis ol tla"4! ua&JI nN adled11lod 1o1
rtClliWG a l.0-mL (10.,.g Hl6A.g) iDb11nlllll•
•c.
ni1lit a t 4 Wuhed, dried beads wue
maintained at -20 •c. T•·o hundred-
the fil'St hwna.a imm~aic:ity- cular lnjectioo ol the :,eut reeo111bi11&11t microliter \'Olul'IMISI of Hra dih1ted 1:100,
salety trial of the yea.st recombinant •acciaa at 0, l, and I moncha. Postvatcine• 1:1,000, and 1:10,000 ia phoaphace--b1&fftred
hepatitis B 'nleeine. To the best oC our tioo blood N111plt1 for the determinatioe saline containiar 0.5CJ5 bovine terum albu•
knowled,e, this is the first time that of hepatitis B Mrolo,ical mukors, A.LT, 111ia and 0~'h Twffn 20 wtrt int11bated
a v&cc:ine prepared by rocombinant ud yeast anr.ibodr wen IICMdultd 1110ath- with coated buda for thrte hours at :rr •c.
DNA technolOID' us Men am in ly for N¥tD montba aad at e. lZ. 11.ad Z4 Following three washes with water, · the
man. months followin1 the firat iAjoctioo. beacla WUN ioc:ubatecl with 200 ,.Lor iodine
VaccilKltl 111ere uucl to take their tem• 125 pNll4iD A. (11p,ci5e adivit)', 100,000
paratun oily for &ve cln111 aftar ooeh cpm) for U houn at 31 •c. The protein A
MATERll:.LS AND fAEYHODS
injgctioo of •accino and to report any loul binds and labola any a ntiyeut antibody on
Popul Uon or l)'a1tmic nactiono tlult 11\ight oa:ur tk<1 ad thnt it of the lg(i clan. After
Putic:ipantll in thil, etudy "'11"' bonlthy, durin11 this period. threa .addi.tional w1tar washes, the beads
nonp,opant adult omployeaa ol Hflf'Ck ero CARted and liun of yeas t antibody
end Ca, [nc. SubjllCU had to bo ti A o ya -•rv detsrmioed by interpolation from a
for hepntiti6 B terOIQ\!ical mnrk~ni ud Stnndard radioi111munol!.lllll!ly t81Jt kit.a ■ tandard curve derived ur.ing dilutions or a
bo"e a normnl lavol of aluino 11111i11~ waro ueecl for tho dotorminotion of hy1)0rimmune 111ina:i pig 1er11m hm.vinc an
· lransferaoo 11.nd 11111st not h11VQ r«oit'ad HlloA1, onti-HBa, and anti-HBc. Titol"SI or lllltibady titor to parent yenst , ~tract or l
nnr othar hepstitio B ••ccine. Writton 11oti-Hllo aoerq uprtllOl!d in i11tern.ntio1Lt.l 111illio11.
Hopotitill 8 \leccmo-Scolnick et al 281:I

OOlBl
The serum 10.mple11 of ncci11H11 wu-11

Tllblo 1. -PropartO'I (~) of Vacc:inooa Wrth Cinicol Comploint• Curing a
alac me111urtd for dwlBH in pr91ln1tins
F ~ y Poriod Follo,oing lr\ieCtiOII of Y OBI R ~ n t Mclpatilia 8 V11ccino
specific yeut 11.11tibodia or tao 11ppara11ce
of a11v yeast utibodi111 aning o sodium VOCCIAO Let NO. 0- 1 0oM 2 Oooe i
dodeql wlfato polyacryla111ide gel tlecuo-
phorasill (Nldacing), W e11ter11 blot tech•
aique. [n this procedure, pannt yeut
txtnlct iB l!lpanltod OD II 12..Sf. poly•
ac,yla11nid1 pl Al&ar traufer ta a 11itro-
eellal09e aheot, pol)'lll!ptidell from the pl "lncluloa , . _ ..., - or - llllieallD8 DI IIIO IO!!owiftO: IMlpl:talln. 31.3 10 38.1 ·c c,o, to
102 'F) (-1. ""lieuo ~ ). ., _ _ , • - _ , (-). - C-1. • - • DI , _
are det«tad by iaeubntioa with e 1:50 . let)' nCI-.. (llwN). end_,_(-). ·
dih1tioD of the TM:CinN's aerum. follo"'ad
b>· iacabll tioa ,ri th ,.I pro&oi11 A and
elll)Ollure to 1-ray lilra (T. lf1111011, PhD, T1b10 2.-S--WOtaion F r ~ anc Geotnolric Mee" rotena (GMTsJ•
oral eommuaieaaoa, 1112). to, Mli·HBe Aft,ong lnilialy ~ t i w c HQellhy .a.dub Ao,;amng 10-,ig
0oaeo of Yeeat F l ~ Hlilpelilill B V■CCftC>t
RESULTS
The vaccine hu been W<.!U tolerated.
None of the 37 ■ubjeeta studied to
date has experienced 11 11Rrioa1 ad-
verse atiect attn"bot&blfl to vaceiH.
There bas been no eridence of hepati-
tis B inlection amoa1 vacciDen, i1, ao
elevation of ALT ftlues and ao uti-
,enemia. Mild sorenaa At the injec-
tion site f41nerally lutinc one to two
days was reported by '7H, to 80~ o(
vacciaees who received YICCine puri-
fied by immune affinity chromatotra- .... _....,_...pg,_.,,
phy (lot 934) but by a 1ubataatially tAIO.t.MIIII....._
smaller proportioa-2011 to 24" -of tA!I - ....,_ __, 11£1'11 et lloll 0.6 111<1./11111, - eociped • ,.i,,,c, of 0.3 lfflU/ffll.. 11>r
1ubjects who received Yaccine pre- _.,.Cll,IT..
pared by ht-drophobic interaction
chromatography (lot 972) (Table 1). Table 3.-P_.oee of Anti•. . . Spocilc lot• &NI d OotermiNln111
Inlreqaeat 11■ temic complaiata oc· ol . .aAq in Poetvac:cinmlion Se,g •
curring within .a five-day period fol•
lotrinf nccinalion have included ele-
vated temperature (38.3 to 38.8 ·c
[101 to 102 •rt oral), Im~, head-
ache, p.strointestinal disturbance,
symptoms of upper l'ffpiratory tract
infection, and DOMblted.
Table 2 cummarius our observa•
tions to date on the humu imm11110-
genicity of yeast ncombiuat bepati•
tis B vaccine. Fi.ft.Ma persons (ten
men, fi•• womea; acre nmp, 23 to
S3 yenn; median &IQ. 33 :,uni) baw
received all thrN dol8tl of lot t3-S
vaccine prepared by the immune Tweaty-two subjects have roeeived t three months. Geometric muo
affinity chrom1togn,pby method. YaccinG from lot 972 made from titeni •ithin the ftrst three months of
Forty percent had II det.t:tablt titer HS.Ag puri.6ed by the hydrophobic Collov-up were ■imilar to those
ol uti-HBn within one month of intraction chro11U1tofrt.phy method. observed among recipients ol lot 9~
receivinr the first doM. By two Thell waccinffll have not bffn fol- vaecine.
months. the proportion ol aerocoa- lowed up for u long u the lot 93-& Postvaccinotion serum u1mples
verter11 rose to 931', and at lhrH recipi nt.11, -.nd noue ha, yet r«eived with nnti-HBll titers oC 25 lmU/mL or
months, oil recipient, of thill vnc:cine third dOlfl. Preliminary urological mater we uaayed to determine
\\·ere antibody positive. The geometric resulw ore shown in Table 2 for 15 or the ~\'cent.age o( antibody spo!cilic
mun titer following primllJ')' immu- thno ,olunteera (12 men, three for the....ll nd d determinants of
nization reached o plate u !lt four women; age range, 24 to 63 yezra; HBsAg. Table 3 shows the results or
months, th n incromsad more th n medion ge, 40 years). The percent&\g(I thesll assays. Antibody specific for
25-fold following the boooter dooo ot or 1eroconverteMl wu 27 1:1t one the a determinant predominates. In
six monthll. month, 67% at two mont.ha, and SO% the interval Crom two to seven
211"1 JAMA. JvttO 1, 1004-Vol 251, No. 21 Hopatilio B V&ecino-ScolnJCk GI al

00182
months followinr the first dose oC no ch.. nse in the yeast antibody pat- is associated wiih vaccine-induced
vaccine, anti-a antibody accounted for tern !or any person s compared with anti-HBs. 1• 11 F11rthennore, one of
approxim:i.tely 90~ of the total anti• his prevactination pattern. There has these trials demonstrated that anti•
HBs. been no appearance of neW' antibodies body formed in response to \·accine of
Earlier 11tudies (unpublished) in postvaccination sera and no siguifi• HBsA1 subtype cid provided cross•
sho-,ed that the yeut recombinant cant increuu in the intensity of protection against infection caused by
hepatitis B vaccine induced a predom• existing antibody bands. heterologous virus of subt}-pe av.•
inantly anti-A form of anti•HBa in Since the antibody lormed by recip-
CONCLUSIONS
African green monkeys and that ients ol the yeast recombinant hepati-
these antibodies hnve J)2rsiglQd The results or this stud)' indicate tis. B vaccine is predominantly anti-a,
through two years oC follow-up. that n alum-adsorbed hepatitis B this nccine should be protective
Anal)·sis of serum samples from v&ecine !ormulat.ed using HB1Ag of against all hepatitis B virus subtypes.
participants in this study hr.a re• subt)-pa adw synthesized by recombi- The efficacr of the yeast vaccine
vealed no significant poatvaccinntion nant yust cells is &afe and immuno- against both homologous ad and het•
increases in yeast antibody titers ll.8 genic for. man. Seroconversion · rates erologoua cii, virus challenge in chim-
measured by radioimmun y. By· and tit&r11 of anti•HBs obtained with panues has been demonstrated."
Western blot nalysis, each human the yeast recombinant nccine in thls Studies are under .-ay to assess
serum sample shows a unique "fin. study n? comparable with thoae antibody persistence and to deter•
get'i'rint" spectrum of antibodiu to obsernd. in earlier studieti of healthy mine optimai do.es of the yeast
yeast components. There may be only adults u11in nccine deri•ed from recombina.nt hepntiti1 B vaccine for
a few or as many aa 20 different human pluma. ..., hi>th healthy and immunocompro-
banda praenL Analysis o! monthly PreviOWI atudin with hepatiti1 B miaed adults and children.
postvaccination serum aamples from Yaccine ·or human plum11 origin
participants in this study bu UOWll 1ho11;ed that protect.ioa from infection
fletor-oa
l. Frum DP: s..i.cu.. primary '-Ith rara: . E:q,...aioe el ...,_cilia 8 Yiru •rf-ulliun 16. ~ S, Han.y HP Jr, 0.-ridlaa ~. tl
S1rwisi111 ror eoatrol •r ~ ia the . . . . . ia yeaat. NtlCIN Aciu . . l_,..ll:2'141-l'lU. al: lll\aaM;ftic tffec& .C iuc\i..lH ha,.&itil B
ins _,Id: !IL Hepadtia B 1'11'118 ud hll rolnl8d I. Miyuobra 4, TM-ci A. Houkl C. at al:
t:.,,e.ioD el MpllUD9 8 Al'f8CI &asiaff ~
.-ia& C-pamoo al 20 •icn.rram aod CO
4 i - . 11ft l"4fe,,I. Dia 1ta;J:a2.m. ...,.... 4-. J M-4 Virot l.l;l:llt-W.
t. Gus& I: Comparma el &lio .,;um.i.., ot ia 18at. 1,- Natl ACM Sci (IS,( ~ l - 6 . ll. Hme■u IU.loa,ukEB.Mu.t.erWZ,n
lwpauua A aad I, ill
Ma,...... JE (eda~
Fraaklia laltiwt.t
V'_,Sul•-
H.,.,..._ W, 41W HJ,
~n..telplai,>.
P-. 1ffl. pp 19-14
10. lllcAloer Wl, lo)'Uk El. ~ 1%. 8t
al: Humu N,-ticia I •aa:im ,.,.. ,-wau,
1-■IL ,:_,. llk:Sll'fzl11-llll.
al: llapolilil, A Uld llupe&itia I --=•11.ill
S . - - W, A.It.er Kl, !llaJHrd JE (fflk Viral
H.__ Pkil6dolplli&, FruicliD lutitut.e
:a. lmmuaiaatioa l'ncllno AdriaooT eo-1,. 11. K.W.r Fl. Adam E. Hei'afl1 D. et at "-.lllZ.Ha-391,
_, lucu..ud liepodoa B Yiru _,.._ A.,. ltolpouo ID llepatitia 8 ,acciao ia a '"-er ad11lt 11. 0..yur J, Colaet\ l, \'emraet.t )I, tt at
Hepaum Bl'Hl:ill&DOII ot u-,hliillca. s.:au J
/u- 11.J lm:tT:r.t-m. popelatiN. ia Saaa- W, A.liar KJ, Me,-anl
•· Hill•au Ml. McAIN, WJ, lu)"'&ak EB.~ JE (ade): Viral H ~ Plliladalpua. Fruklla Jr,,/occ Ou lta;Jlltuppl):'2-4
a~ Q,,ali&J &11cl 1&11111 er 1111- llepa&ilio B lu&i&at.t Pna. 1-. Pf1'5l ◄IS. 11. s.m- W, S1ew11t EC, Z&ar EA, tt ~
,raft:iM. 0..Jilal S,.IN! lta;M:S-U. U. Holl.._io lH, G•lff7 JU, Saal....... I..A, A -cnllod lrilll of die 1llcacy or tilt bepatilis
, . krnll CJ. libcliaJ P, c,_..,.,. PJ, et al: et al: SoallcnlilC et llepaci&ia I _,,_ a■ u,n I ftCCiM (HopeaYU I): A laal report. H.,,._
£ap,tilioa i• £auPic.liie roli el MJN)&i&ie I ucl uui-Sy 11T radioi■--,. a...,_. ...... 1• 1:i:m-m.
rirua DS4 MIi"•- clNICI ia p&anaicl pBJtm. ......_,, l f f l ~ - - 11. Frucie DP, Hadler SC, Tbo111peea SE. u
NOlvn lt'i't",219:41-41. · a.
U. O.iallanlt F, 2.aellffal r - r H. at al: al: TIM, ...-•lie•el llepoli&ia I orich •acci1111:
'- ValeU11ela P, Cray P. QuiNP M. et al: P■um•KU911 lmmuisalioa api1111t lMpe&iD11 I. ~ t4 the Caaten lw Diuua Conuol cnufli.
t.11el-.4e ......... .t ""' ,..,. codill(? r... 11M ia Enocmu S. SIIDrlock 5 (od9k P.m1-i1g, .r - - tlilcacr uial &-■IJ
1n11jor Drat.ti• or MpadUII B l'\l'U lllrfHID uti• lb £.....,._ .s.,_,__.. .. H#IJMNill NC1<11 A.. 1-.11.t l912;t'f:Jlt..._
ilNINaX11al 11\01\.
119•· ,\·e11m, lt19:280'JlMlt. York, ICPl laforll!odia ~ lRl, Ill. Saa- W. S&tftu CE, Harley £1. tt al:
1. Vale11111ala P, Median A. Ruan WJ, o& al: pp 140-150. H-,aci&ia I ftCdao ia m,dial awf or hemodial-
S1·11tARia and .-111bly or hopaticia I 'lino l'- S-•- 'It, 5 - u Cl:, Harlof EJ, ot al; 7"1 Hill!: Elllcac7 ... subtype crm ,proltcliOII.
811rfaa a11titr9a ,onicla ia JOUl. Nua,o ltn; Tll:i ia ■UI , . , . _ ol lln!Uiy ...1111 Ml a N Efltl{ J MN l~:1411•1-
111:31,-350. roduecd-. el illpa&itit B n.ceiN. J lied Vitel
B. Hitum11n JU, Clwi• CY, Hap, Fl:, et al: l l;l;IIS-1111.
Scolnick E , JkL ft Mo $t OJ, cA1 J, ~iller ~J. Gu~ k EG. C11n1c 1

V lU&tion ifi h lt~i dults of p t1th G v cc1n cf -by r~cminilnt
D~A. ~ 19 ; 251:2812-15.
JAMA. J.,no 1, 1'1G4-Vcl 2$1 , Mo 21 HopaIiIio 8 llaccino-Sco1nic:li 01 &I 2815

STUDY 792
00183
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepat1t1s B vaccine,

Study 792

serologic markers.
YACC INE: Yeast Recombinant Hepatitis B Vaccine

Lot 1934/C-J625 (10 mcg HBsAg/ml)
Lot #979/C-~564 (10 mcg HBsAg/ml)
PRINCIPAL Jules L. Dienstag, ~.D.

Fruit Street
Boston, ~A 02114

Fruit Street
Boston, MA 02114
Fruit Street
Boston, ~A 02114

Fruit Street
Boston, MA 02114
25271
12/20/85
00184
Study 792

personnel of either sex {excluding pregnant women),
who were negative for HBsAg , anti-HBc and anti-HBs,
had a nonnal ALT level and had not previously received

intramuscular injection of vaccine oroduced by the
i11111Une affinity or the (b) (4) proc edure at 0,
1 , and 6 months. Vaccine recipients are asked to
record their temperature daily for five days after
each injection of vaccine and also to record any local
or systemic co111plaints that they may have during this
period.
A blood specimen (10-15 m1) was obtained from each

vaccination and on the day of the f1rst vaccination.
subjects vaccinated with lot #934/C-Jf>25.
Post-vaccination blood samples are taken at l, 2, 3,
f>, 8, 12, and 24 months from persons injected with
vaccine lot #979/C-K564. The samples are assayed for
HBsAg, anti-HBc, anti-HBs, yeast antibody and ALT.
Samples with anti-HBs titers ?, 25 mIU/ml are tested
for the proportions of anti-! and ant1-~ activity.
STUDY RESULTS: HEALTH CARE PERSONNEL (b) (4) Vaccine):
10 mcg lot #979/C-K5f>4 at O, 1 . and b months
Injection No.
_ l_ _2_ ..J_
35 35 32
25271 - 2
12/20/85
00185
Study 792

participants at nine months. Seroconversion (S/N
~2.1) for anti-HBs at 9 months was 96% (27/28).
Ninety-three percent (26/28) of the participants
~10) at that time. The GMT at nine months was
531. 1 mIU/ml for a 11 vaccinees and 82&. 3 mIU/ml
for responders with a titer of mIU/ml ~10.

months, 83% ( 20/24) were positive for ant i-HBs
(mIU/ml ~10). The GMT at that time was 234. 1
mlU/ml for all vaccinees and 403.0 mIU/ml for
responders with a titer of mIU/ml ~10.
See Table l for anti-HBs responses and GftllTs for

Clinical follow-up data are available for all

Type of
Complaint
Injection 20(7/35) 23(8/35) 25(8/32)

Site
Syste11ic 14(5/35) 11(4/35) 9(3/32)
Refer to Table 2 for listings of specific

clinical complaints by injection number. Maximum

attributable to the vaccine .
PUBLICATION: D'lenstag JL, Watk.ins E, Hinkle CA. · Recombinant yeast

hepatitis B vaccine: immunogenicity and safety.
25271-3
12/20/85
Table l
ANTI800'f RESPONSES FOLLOWING VACCIIUTIOH WITH R£COt18IHAHT HEPATITIS 8 VACCINE
STUDY 0792
POPULATIOH HEALTH CAR£ PERSOWNEL
DOSE 111 11C6
LOT CIC564
l!f'GUIEH O, 1, AHO 6 MONlllS
ltllTIAl 9tROLOGY NEGATIVE
I Y. WITH 11.HT!-tftlS I GHT IHIU/11ll I

l---------------------------------------l-----------------------------------------------------1
I I I RESPOtmERS I
TIHE l---------------------------------------1-----------------t-----------------------------------l
Ct101lTHSl I SIN n 2. l I HIU/Ml >: 10 I All VACtlllHS I SIN >= t .1 I PIIU/f1L >= 10 I
••••o•••••••••••••••••••••••••••••-••a••••••••••••••••••••••••••••••••••••••••••••••••••••e•••••••••••••••~•••••no
I
! ttONTH nx UO/lftl 5.9)( 12/lftl I 1.1 7.2 I 711.6
I I
t ND>ITHS 8111. Ull/321 75Y. 124/321 I 24.5 "3.4 I 65.,
I I
l t10tOH5 91Y. Ct9/lt> 8lY. 126/321 I tiS.l '3.4 I el.l
I I
6 l10t1THS 971. 129/JOI 97Y. 129/lOI I 72.ft 84.0 I 84.0
I I
9 HOtlTHS 961. CH/ZIii 93)( 126/281 I Slt.l 67t.7 I 8Z6.l
I I
12 l'IONTHS 921. 122/2" 831. 120/241 I 234.l 403.0 I 403.o
I I
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
-
0
0
a,
a-
Table 2
PATIENT COU~T CLINICAL COHPLAJHTS
RECOffllttlANT HEPATITIS 8 VACCIIIE
STLDY 079:?
TRE ATHENT
LOT NlR1BER Cll5 H
DOSE I 10 t1t8 .
PATIENT CLASS: HEALTH CAR! PERSONNEL
I TOTAL VACCJN£ES C 35 PATlEMTSI - OOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST VACCltlATIOH I NUHBER
CLINICAL
tOffl'LA IHTS
l----------------------------------------------------------------------------1
I o I 1 I z I :, I ,. I , •
WITH
•c0t1PtAIHTS
•••••••••••••••••••••••1>11•••••••• •1••••••••••1••••••••••1••••••••••1••••••••••1•••••••••• •••••••••••••••••••••••••••••••••
9
I I • I I I I I
REACTIOH, LOCAL IIHJECT, SITU I 6 I Z I 1 I l I O I O I I 7
, , 11.1;,;, IC 5.7i!I I C Z.9%1 I I z.,:t.l I I o.o:o IC 1, 0% 1 I IC 20.0:t.l
-----------------------------------l----------l----------l----------l----------l----------1----------1 ----------1-----------
PAIH I 1
I c
I
I O I I I
z.,::-:1 I , o.or.1 I
I
t
•
I
I
O I
o.ox, I
I I
I
1 ,.,x, I•
I 1
I o.ou I ,
I
1.,x1 I
I
I c z.•:t.1
I
SORENESS I !J I Z I l I 1 I o I t I I 6
I I 14. J;( I I I s. T/.1 I I I. 9Y. I I I Z. 9;( I I I O. 07. I I C I. 0,0 I I C 17. li! I
----------------------------------1----------l----------l----------l----------l----------l----------l----------l-·---------
sysTEHIC I t I J I 2 I 1 I O I 1 I I 5
I I 5.77.1 I I 9 .6:f. l I I S.T/.1 I C t.9%1 I C o,o;o I I !,,./.I I I I l 't.J:f.l
----------------------------------------------------------------------------------------------------------------------------
eetOLE BODY/GElaRAL I
I
1 I 2
• I I 0 1 I .,
t.9%1 I C S.T/.1 I 0.0% 1 I O.t:t.l I I e. o:o C 2,,-/.1 I C 11.to:t.l
I I I
SMEATJHG I l I 0
2.9%1 I C 0.0:t. t C
0
0.0%1 ( • I 0
0 .0:t.1 I 1 o.o:;o I
e I
1 .0:t. 1 I C
l
1 .9% 1
I I I
HALAJSIE I 0 I 2 II 0 I 0 0 I 2
0,0%1 I I 5,T.O 0,0%1 ( O. OY. I o.ox, 1.er.1 I C 5. 7)0
HfllDACHE I 0 1
C
0 9
' 0
C
1
I
I f
I I 0.07.1 I 2,9,0 I o.o:o ( 0 .0%1 I 0.07.J I 1.,;c1 I I 5. 7% 1
I I
INFECTIOUS STtllJIHIH!S I •
0.07.I C
e
0.01.1 I
e
0.07.t I
1
Z,9i0 C
0
,. ox, •
o.or.1
I
I (
l
t.9:t.l
' I
INFLUENZA, NOS I 0
o .ar.1 •
0 , 8 Y. I (
0
9 .IY.) I
1
Z.9Y.I C
0
O.OY.I
0 I
I
l
2.9Y.)
II '
C
' O.Oi!I
I
C
KU!CULOSICIEUTAl I 1
2.9i0 C
1
t.97.t I
1
r.,x, I •
O.OlO I
0
O,OY.I
0 I
O.OY.I I
l
t.9Y.I
'
( Q
" YA lCU i 1 1 1
• 0 0
I
I l
...
Q
( t. 9'/. ) I 1.9:f.l z .,:t.l ,.ox, I o.o:o 1.0?.1 I ( t.,?.I ...,OD

'
( (
Table 2 (cont)
PATIEHT COUNT tltHltll tot1PUINTS
RECot18INANT HEPATITIS 8 YACCIHl
STUOT : 01,t
lREATffl:HT
LOT NUffl[R I C~564
oo,E r 10 nc&
,ATIEHT ClASSr HEALTN CARE PERSONNt:L
I TOTAL YACtltll:ES I 35 PATtENTSI - OO!E 1 I

l----------------------------------------------------------------------------1
I DAYS "'"' VACCIHATJOff I NUNBER
CLINICAL
COtlPlAIHTS 1----------------------------------------------------------------------------I
I O I 1 I t I 3 I " I S I MITH
ICDtfPlAIHTS
•••a•••••••~•••••••••••••••••••••~•I•••••••••• •••••••••• •••••••••• ••••••••••••••••••••••••••a••• aa••••a••~ •••a•••uaa
I
DIGESTIVE SYSTE" I O 1 1 0 0 D l
o.o;o I Z.'1)0 I Z.9'0 I o.o;o I I.OY.I I o.o:u I Z.'liO
NAUSEA I O l l 0 0 a l
0.01.1 I 2.,;o I Z.'17.1 I a.ox, I o.ox, I t.OXI I 2.'11.)
NERVOUS SYSTEN I 1 I 0 0 0 0 l
l!.91.1 I 0.01.1 C 0.01.1 I t.0lO I 1.01., I o.o;o C !.'11.>
VUITJGO/IJllZINtSS I l I O O O O 1
I I t.9i0 I 0.0iO I I O,DY.I I I 0.01.1 I 0.01.1 I 0.01.1 C t.9%)
-------··---------·-·--------------l----·-----l----------l----------l------·---l----------l----------1----------1-----------
PUISON! einH tOHPt.AINJS I a I s I 1 I r I o I 1 I I u
I I U.9)0 I I 1,.1;:1 I I 8.6i0 I I s.r.o I I t.01.1 I C !.91.t I I C ]1.47.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEASDHS 111TH HO COtlPLAINTS I l!7 I 31 I 3Z I 33 I JS I 3" I I t•
I c 11.11.1 I I 85.7'0 I c 9l.4i!I I I 9".31.1 I 1100.0;0 I c 97.11.1 I I I H.1>1.>
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
PERSOtfS MITH HU DATA I O I O I O I O I O I I I I 0
I I 0.01.1 I C 1.01.1 I C O.OlO I I 11.1;:1 I I O.OlO I I 0.07.t I I I 0.01.1
-
0
3'
011
Table 2 (cont)
PATifNT COlffl CLINICAL CONPLAINTS
RfCDMBIHIINT HfPATITIS 8 VACCINE
SnJIIY 01,z
TftATI1£NT
LOT ttUHBtR I C1<564
bOSE 1D tlCG
PATIENT CLASS: HEAL1H CAR! P!R!ION!fEL
I TOTAL VACCINE[! I lf PATIENTSI - DOSf ! I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I HUtlB[R
CLINICAL
CDHPLAINT!I
1----------------------------------------------------------------------------I
I O I 1 I 2 I J I 4 I !J I
MITH
IC011PlAlHTS
•••••a•••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION. LOCAL !INJECT. SITU I 7 I 2 I Z I 1 I o I o I I 8
I I H.OlO It 5.T/.1 IC S.77.1 IC 2,97.I I I 1.0Y.I I I O.D7.1 I It H.'17.I
-----------------------------------l----------l----------l----------l----------1----------1----------1----------1-----------
sORENUS I 7 I 2 I Z I 1 I I I o I I &
I t 20.oio I t 5.nl I c S.77.1 I c 2.9l0 I c 0.17.1 I t o.ou I I c 22.,1.1
-----------------------------------1----------1----------1----------r----------1----------1-------- . ,__________ , __________ _
Sl'STEHIC I 2 I D I 1 I O I 1 I D I I 4
I ( 5.7)0 I ( D.o;o I C 2.97.1 I C O.DY.I I ( t.,;o I I o.o:o I I CU.47.1
l!HOLE IIOOY/GEH!RAL I 1 0 I D 1 0 2
2.97.1 I 0.0)(1 I o.o;o I 0.117.1 ( 2.97.1 I 9.0Y.I I 5.T/.1
HUDACH!! I
I
l
t.97.1 I
0
1.07.1 •
O.GY.I (
0
11.07.1 I
1
Z.97.1 I
0
1,11)(1 (
I!
!I. T/.1
IIUPll!ATORY I I 0
' 1
• • I I
.
'·''° I 0.07.1 ( 2 •..✓.I
' 0.07.1 I O.GlO I 1.01.1
• Z.'ll!I
llfflHlTIS I 0
O.Ol!I I •
0.07.1
1
t.9'/.1
0
11.07.1
0
1.07.1 I
e
1.01.1 I
l
2.,x1
I
' '
M(IIIIOU!I SY STU4 I 1
2.97.I ( •
0.07.1
0
,.o,o 0
o.or.1
0
11.07.1 "
o.oio I
ll
2.,r.1
I'
VERTIGO/DUZIHES!il I 1 I II I ' O I ' II o I I I I
' 1
I I Z.97.t I I 0.07.I I I 0.07.t I I 0.117.1 I I 0.117.I I I O.OJCI I I I Z.9l!I
-----------------------------------l----------l----------l----------1----------l----------1----------1----------1-----------
PEl!Sons MITH COffl'UINTS I 7 I Z I ] I I I I I I I I 9
IC 211.01.J 11 S.TI.I I I 8.61.1 I I Z.91.1 I I Z.9)(1 I I 0.17.1 I I I U.77.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEllsom ~n" NO COffl'LAJHT9 I 28 I SJ I 12 I ~ I l'I I 35 I I 26
I I 110.07.1 I ( ,~.l7.I I I 91,41.1 I I 97.17.1 I C '7.17.I I UOl.117.1 I I I 7lt.]7.I
0
-----------------------------------t----------l----------l----------l----------1----------1----------1----------I-----------
PERSO'HS MITH NO DATA I
I I
O I O
O.D7.t I I
I O
0.17.1 I I
I t f
O.OY.t I I
O I O
0.117.1 I I
I I
0.117.1 I I
II
O.O:O I I I O.DY.I -
0
0,
"'
Table 2 (cont)
PATIEHT COUNT CllHICAl CottPLAIHTS
RECOt81NAHT HEPATlllS 8 YACCIHt
STUDT I 07"2
TREATMENT
LOT HUl'IBEA t CK56"1
DOSE JO NCG
PATUHT CLASS: HEALTH CARE PERSCltltl£l
----------------------------------------------------------------------------------------------------------------------------
I TDTAl YACtlffEU I 32 PATIENTS I - DOSE :S I
1----------------------------------------------------------------------------I
I DAYS POST YAttlNATIOH I HUHBER
CLINICAL
C011PUIN1'S
1----------------------------------------------------------------------------I
I O I l I Z I :S I "I I 5 I lt11"1'~ITff
LAINTS
uuoa••oaaa•a••••••••••••a••~••••••• l ••••••••••l• ■ •a••••••l••a ■ aa••••••••••••••••••••••a•••••••••••••••••••aa•••• • ••a•a••aaa
I I I I I I I I
REACTION, LOCAL !INJECT. SITE I I 6 I J I 3 I o I I I O I I 8
I • 1e.e:r.1 I • 9."17.J I 1 9.4:o I I o.ox, I t o.or.1 I I e. o;o I I t n.11r.1
-----------------------------------1----------l----------
PAIH I o I l
----------
l
----------
o ----------
t'J
----------
e ----------1-----------
I l
I • o.o:n I 1 :s.uo , J.uo I o.or., 1 o.o:o I o.oiCJ I , J.1;0
I I I
SO!lEHESS I SI l 2 O I o I 6
I I 15.61.t I I J . I XI I 6.lY.J I 0 .07.J C 0.11:0 I t.07.1 I C 18.li!I
I I I
TEtmERHESS I II I 1 0 O o o I l
I G 0.07.1 I I J.ll!l I 11.07.J I 0 .07.1 C 0.07.1 I , .e;o I I ].UO
I I I
l'RURITIS U TCHIKB I I I I O O I O II I I
I I J,17.1 I I 0.17. I I 1 .07. 1 I 11.07.1 C O.liO I 1 .01. I I C :S.UO
----------------------------------- Il----------
snnn1c 1
l----------
I I
l----------l----------l----------l----------l----------l-----------
I 1 I 1 I 1 I l I I J
I I J.lXJ I I e .07. J I I J.17.1 I I J.11.1 I I 3.17.1 I I J . ll!t I I I ,.~;n
ta!OLE BOtJT/G!N[RAl 1 0 I 0 D 0 D l
3.11.1 I o.ox, I 1 o.o:o I 1. 07. 1 I o.ox, I 0. 01. 1 I 31.1:0
I
ffEA'OACHE l
3.liO I
0 I
c. e:r., I 1 •
o.o:io I
II
1!1.07. ) 1 •
O.OX) I •
0 ,07.I I
1
31.17.1
I
o. • •
RHPIRATOffY I l l l l 2
ox, I 0.17.1 I I
I
J . 1)0
• J . 1:r. ,
• :S.l?. I I ll, 17. I
' 6.37.1
PltARTKl:lTI9 I SCll'f THROAT I 0 0 I l l 0 0 1
o.o,o I O.IXI I I ll . llO G J.UO ( 1,01.1 I 9.17.I ( J . lXD
I
UPPER RESPlRATOltY INFECT., HOS D
0 .07. 1 I •
1 .or.1
I
I ,
0
0 .0:r. 1 C
0
11.0:1.1 (
1
J.i:o I
1
:S.U!l I
1
J.17.1 0
mJSCUl.OSltElETAL 1
•
I
I I
• II
• l
...
0
J . 17. 1 I 0.1:r.1 I I 1,07. J I a.,x, ( 0.117.1 ( O.D?. I I J. 17. 1 -0

0
Table 2 (cont)
PATIENT COUHT CLINICAL CCIHPlAIHTS
RtCot!BJNlNJ HtPATITl!I B VACCIH£
!ITIJDl' I 1792
Tl!EATN[NT
Lor NUtl8£R l C~561'
DOSE 10 t1CG
PATIENT CLA!IS : HtA LTH CARE PIR!ICMIEL
I TOTAL VACCIN£E!I I 3Z PATJENT!II - DDS[ J I

I•----------------------------------------------------------------------------1
DAl'!I POST VACCIHATION I IIUl1l!ER
1----------------------------------------------------------------------------I
CLJHICAL
COHPLAIHTS I O
..............................................
I
I
, l
..........
I
I Z
, f 3
..........••.........
I
I
I
1'
.......... I S
,
..........
I
I
, Mint
.......... •cmPLAINTS
I
.......... ,
I
,
I
ltYALGIA I l I O I II • G • 0 I O I • l.
I I 1.11.1 I I o.ou I t o.olo I t o.oY.> I , • .o;o • , o.oY.> I I • J.1x,
-----------------------------------1----------1----------1----------•----------1
ptRSOOS Nlllf CottPUIHTS I 6 I J I J • 1 I
----------1
l •
----------1----------1
1 I •
-----------
9
I • 1&.eY.1 I c ,.-.io I , , . ,.Y.1 I c 1.1Y.1 I • 1.1Y.1 I ·c 1 .1Y. 1 I • • te.uo
-----------------------------------
PERSONS MITH NO COt1PUINtS
1----------l----------l----------l----------•----------
I H I n I n I 11 I n
•----------•----------•-----------
I n I I n
I , e 1.1Y.1 I c ,o.,Y.1 I , 90.6:o I • 96. , :o I 1 96 . 9)(1 I 1 96. t )(I I I c n.n,
-----------------------------------1----------1----------l----------l----------
"fllsms !!'ITlt NO DATA I o I • I e I •
l----------l----------l----------l-----------
I o I o I I o
f C e.o:o I f 0.11.J I I O.D)(J I I 0 .0)( 1 I I ,. ox, f I I . O)( J I I f , .o:o
--
0
-0
Table 3
PATIENT COUNT "A>Clffl.tt TEffl'ERAlURES
RECot18INAHT HEPATITIS 8 YACCINf
ST\IUT t 0792
T1'EA Tnl:HT
LOT HUlfflER I CK5M
DOSE I 10 HCG
PATlafT CLllSS: lt£Allff CME P!RSOt&IH
I TOTAL VACCINfES t 35 PATIENTS) - DOSE 1 I

1---------------------------------------------------------------------------------------I
• DAYS POST 'IIACCDIATION f HUtmER
"llX TEHPERATURE
CDEG F , ORAL I
f---------------------------------------------------------------------------------------1
I 0 I l • ll! • J I 4 • 5 • •
MITH
I NAX TENP
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••t••••••••••t•••••••••••••••••••••
• I
< 99 • H I ta I• Jl
I
I ll
•
• H
I
• u •
I I
I 15
I 1 11.4,o • t M.&7.1 I I ae.67.t I 1 ,1.t7.t I 1 11.s:u • c n.aio I • c 1ir.,x1
I I I I I I I I
,, - '"·' I 10 I 4 • J • J • a • a I • 18
• I ll!8.6)!) . • ( U.1%1 • C 8.67.1 • I e.a:o • C n.57.t • ( ll!4.UO I I t Sl.4:0
I I I • • I . I I
Ult - 100., I 0 I 1 I l • I I o I I I I 2
I C 0.07.t I I J.07.t I I Z.9'tt I I 1.17.t I I ,.on I I 0.07.) I I I 5. 77.t
-----------------------l----------l----------l----------l----------•----------1----------1---------------------t-----------
TEHPERATURE TAKEN I 35 • 33 • 35 • 34 • ]4 • JJ • • 35
I uoe.07.1 • 1 M.11.1 • 1100.07.1 • , ,1.uo I c u.u, • c 9".J7.I • • uoo.o;o
------------------------•----------•----------1----------•----------•----------•----------•---------------------•-----------
TEHF'tRATUIIE HUT TAKEN I O • 2 I O • 1 I l • 2 • I I
I I 0.07.1 I I 5.77.1 • I o.oxt I I ll!.91.t I I ll!.97.t I C 5.T.1.1 • I ( 0.07.1
-
0
, 4)
I\J
Table 3 (cont)
PATIENT COUHT 11AXIHUH TENPfRATffllES

RECOl19INANT HEPATITIS 8 VACCIHE
snm, 1 01,2
T1'EATl1£HT :
lOT NlmBER t CK564
DOSE : 10 11C5
PATIEHT CLASS: HEAlTH CARE PER!OHN!l
I TOTAl VACCIN£ES ( 35 PATIENTSt • DOSE 2 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I NUt19ER
HAX TEHPERATUIIE
I DE& F • ORALI
1
I
---------------------------------------------------------------------------------------I
O I l I 2 I 3 I 4 I 5 I I
WITH
I tux nHP
aaaaa••••••••••••••••-••••••••••••••••••••••••••••••u••l••••••••••l•••••••••••••••••••••l•••••••••••••••••••••l•••••aaaaa
I • • I I I I I
< 99 I 21 I :,o I 30 I n I 26 I 11 I I 1e
I , 19.4Y.J I , es.r1.1 I c as.r,o I , ea.,1.t I c 76.!l>:t I c n .21.1 I I I u.,Y-1
I I I I I I I I
" - H.9 I 1 I s I s I 4 I 1 I l I I 11
I I H .6l!I I I 14.3i0 I C 14 .31.I I C U.4)() I I 21.6i0 I I 8.117.I I I I 45.TI.I
I I I I I I I I
1110 - 1011., I o I o I o I o I l I o I I l
• ( t.O?.J I I O.O)(t I C e . 01.1 I I 1 .01.1 I « 2 .91. t I I o.o:o I I I 2.9?.I ·
------------------------1I ----------1----------l----------l----------l----------l----------•---------------------•-----------
lElff'fRAME TAKEN 34 I 35 I JS I JS I M I 14 I I 35
• I 97.llet I n oo.o:o I UOl.ll!I I 1100 .0:0 I I 97.Un I I 91.l)(I I I 1100.0Y.t
------------------------•----------
tu1PERATU11E KOT TMEN I 1
l----------l----------l----------l----------l----------l
I o I e I • I 1 • 1 I
---------------------•-----------
I •
I ( 2 .U t I I 1.01.1 I I O.tY.I I I o .OY. t I ( !.91.1 I I 2.9?.I I I I o.o:o
-
0
-D
~
Table 3 (cont)
NAXlltlltt TIENPER ATtnlES
PATIENT COIMT
R£COH8INANT HEPAT ITIS 8 VACC1N£
STUDY I 0 792
TIIEAffl'ENT
LOT tlUtillER I Cll.561/
0091E lO l'IC8
PATJ!NT ClAS9 1 HIE AlTff CAIi! Pfltsmaf( L
I TOTAL VACCINIEES I lt PATJ ENTSJ - DOS£ J I

Il--------------------------------------------------------------------------------------1
DAYS POST VACCINATION I NU18!R
Il---------------------------------------------------------------------------------------1
"AX TEt1PIERAT\JlllE
10 £ 6 F, ORAU
I
O • 1
I
I t I
I
J • It I 5
I
• •
I
,
NI TH
• 11AX TIEl'P
................................................................................. ..................... .......... ..........
I I
, ,
I
< n I re I ta I ta I 211 • I u • t1 I I u
II ,o , J1.J II 9J , l?.J II 9J . 3:l! J I I 9J. 3Y. J I C 81.SlO I I '3. l r.J I II 65 .6X J
I I I I I I I I
9, - 99.9 I t I t I t I t I s I t I I 10
I t 6 .5l0 I I 6.7l0 I I 6.7r. J I I 6.7r.J I I 18 . !JXI I C 6. 91. J I I I ll .J,c,
I I I I I I I I
lD0 - 101 . 9 I l I 0 I 0 I I I II I I I I l
I , J .t7. J I , ,.or. , • 1 o.ox , I , t .o,o I c 1 . 11.1 I I o.tl! t I I 1 :J. 1x 1
------------------------l----------•----------l----------•----------l
1u1n1tATtllflE TAl(IEN I n I ,o I :,o I 10 I----------l----------l---------------------l
u I n I I-----------
n
I I '6 . 97. J I I 9J.8l0 I I 93 .BZ I I I '3 . 8 l( J I C lllt . 47.J I I ,0.6l! I I I 1100 . 11.1
------------------------l----------l----------•----------
TU1PERA1Ulll! HOT TAl<IEN I 1 I t I t
I----------I----------I----------I---------------------
I t I 5 I 3 I
I-----------
I 9
I I 3 , 1)() • I 6 .37. I I I 6. lX J I I 6 . ] XI I C U . 6 l!l I I 9,4:0 I I I o.o:n
O ·
-
0
-D
.r:.
00195
l£CO!GlMMi n:,.sy l'ID'#.'UTlS I VACC?Nl: UK.'JIQC;DflCITY Al'-"'D

SAFm. Jl Dh11su1 1 [ 1,;ulttna 1 •nd CA lllaltle • .
Caottoiatest111al Un1t, r.111aachueatt1 Ceaeral loe,ttal.
&oat.on, M. .
Cvcbc11MIIQ<I to pro4,ace, •lt?•n•1.,, , a1Ml lialt.•• 111
aupply, cvrrencly av ■ 11 ao1• h.,..a pl••--••r1••• bepacit.lo
~ vacc1a•• ar• 11~•17 te k r-,lacu 1B the f•t•r• \7
•1•11et1ca llr a11g111acr•~~ ••ccia••• laca11tl7, •
recc,1101Ji.11t D~A •eccl•• va, prepared 1D rec111111\ia&at J•••t
Sacchar..•c•• cara•1•1•• ttra1a 21*2-l call• cransfor-4
v1t1' tlle plaa•lll pilJ5 ~>.1)47/33, conda1a ell• ,._.
for hepac1t1s l.evrfacc ant11•• (HlaAg/.!,!) (Valauvel.a et
al. Jacara l912; 298:l,7-SO), hrl!Sc4 lly \loc;balcal -4
blophyalcal 1t:11t'IM>,l1 frlllil th• r•••t aatr•ct, cbe D ■Aa
particle• 1yiathe1lccd \y th••• r•••t call• ara Ht
glycosylat ad \vc ochervi•• ar• 111411atiacuiauol• fr
aa t1•• 22 110 RlaAg parclcl••• Treated with foriulu Ga4
adaot\ell to al.a, the r•c-•ll\ant ••eel•• 11 1JD,mo1••1c
and proc ■ cc1•• 111 axp•r1.l>cata1 utula. V• ata1a1at•r•4
chro• 10 vs •••ca of the rocn\lnanc bcpettti• l.•accue
(Herek S~arp 6 Dollsie l•••arch t.aboratorle1) et tiae 0, l,
and 6 aoncha to 60 1aro11egati•• a4ult health vorkers. flae
fr~quoacy and a• ocrtc moan tltor (a tV/al) of aac1-U
TOl~OftlCI VtfO & ■ foll-:
tlo11tll l 2 3 4 ) 6
ll\a.._f l7 2' JO 29 •Z) 16
ant1-\Ule• '1% • 13" tlt . 971 ' '61 ,,:
~ ~ 51) 7: 2 Jl l S )6 ! 4 46: 6 55: 4 ,, : 4
,, : 9 (11ea11 : .Si>) f ef the a•atl•llla vas 1pcciUc hr the "
a ••t•m1a&11t of Kla4g. Olaa1•• 1a a:1t11NMtie1 to yaaat
uc11•1111 vau ae1l11tble. The aoac he1111nt "'"'u
rcactioa va, craaaieat • •r•n••• et tMI Slajectin a1te 0
occvrr1a1 after 521 ef flrat, 371 of aecm, aad 5S% of
chtr• 1aJacc1oaa. Ko ••rloua ••••r••tf!ecc1 ••r•
ancoU11tered, a1MI acichcr t)'pC I ••r aoe-S hopac1t11 11.aa
occvrre4 1• Pf vacctaee. Tllcaa prels.a1ut')' re111lte
,-.netrata tha t th• recN1\iae11t :,•oat h•P'tici• I •acciaci
11 safe one! tbat 10 vs oC the rccam~1-..at ••cci11<1 1e
oqu1valcac 1a _..nogoa1clcy co 20 VI of tM
pl1fll4-4er1••• vacc1a4.
Di~nst ~ JL, tkins E, H1nkl CA. BQc 1~nt ~Q st he~_t1t1s E v1ccin

t no9 nicity nd sf t~. JWpf1toloru, lt~; :1077 ( bstr~ct).
,er
°',...
>-
Q
....
:::,
Cl)
PROGRAM: Yeast Recombinant Hepatitis B Vaccine, Study 794

vaccine among:
1. health care personnel who are negative for
2. health care personnel ilillllunized with plasma
derived vaccine who were nonresponders (ant1-HBs
negative)
VACCINE: Yeast Recombinant Hepatitis B Vaccine:

Lot 14J72/C-K444 (10 mcg/HBsAg ml)
PRIMARY Harvey J. Alter, M.D.

INVESTIGATOR: Chief, Immunology Section
Clinical Center Blood Bank
National Institutes of Health
Bethesda, Maryland
SECONDARY David Henderson, M.D.

INVESTIGATOR: James Schmitt, ~.D.
~s. Deloris Koziol
Ms. Beverly Elder
STUDY LOCATION: Clinical Center Blood Bank

National Institute of Health
Bethesda, Maryland 20205
DATl INITIATED: April 12, 1984
DATE COf:'lPLETED: In progress

personnel of either sex (excluding pregnant women) who
are negative for HBsAg, anti-HBc and antt-HBs, have a
normal ALT level and have not previously received any ·
hepatitis B vaccine. It also includes 11
nonresponders to plas111a-derived vaccine.
25481/0091 I/1
1/18/86
Study 794
PROCEDURE: Health care workers receive either 5 mcg or 10 mcg

doses of vaccine at 0, 1 and 6 months. Nonresponders
receive 10 mcg doses at 0, 1 and 6 months. All
injections are 1ntramuscular. Part1c1pants are asked
to record the1 r · temperature for 5 days after each
injection and note any local or systemic reactions.
Blood specimens are obtained prior to vaccination, and
monthly for 7 months and at 9, 12 and 24 110nths post
initial injection. All samples are assayed for
anti-HBs, anti-HBc, HBsAg and ALT by Dr. Alter.
Samples with anti-HBs titers~ 25 mlU/ml may be tested
for anti-a and anti-d activity at ~SDRL.
RESULTS: HEALTH CARE PERSONNEL:

10 mcg Lot #972/C-K444 at 0, 1 and 6 months·
S mcg Lot #972/C-K444 at 0, 1 and 6 months
InJect1on No.
Dose Level _1_ _2_ __L_
10 IIIC9 41 40 40
5 IIIC9 30 30 28
2. Seroloqic Results:
participants who received 10 rncg injections and
for 25 who received 5 mcg injections at 7/8
months. Seroconversion at 7/8 months was 94%
(34/3b) S/N ~10 among those receiving 10 mcg
doses, with a ~T of 160.8 and 209.3 for all
vaccinees and responders , respectively.
Among the recipients of 5 mcg doses, 76% (19/25)
had seroconverted, with GMT's of 54 and 152.9
respectively. Table 1 shows seroconversion rates
and GMT's for up to 12 110nths of follow-up.
25481-2
l /18/86
001 cm
Study 794
RESULTS: (Cont.) 3. Clinical Complaints:

Clinical follow-up data are available for 41, 40,
and 40 participants fol lo\oling the first ; second
and third injections of 10 mcg doses, and for 30,
30, and 28 participants following the first,
second and third injections of 5 mcg doses.
Specific complaints and maximum temperatures
reported during the 5 days following each
injection are provided in Tables 2 through 5.
Dose Freauency: In 'L bx ln~tion

Type of Ccng>1aint ~ 1 2 3
Injection Site 10 mcg 25(10/42) 8(3/40) 23(9/40)

5 mc9 13(4/30) 10(3/30) 14(4/28)
Systemic 10 mcg 18(7/41) 18(7/40) 10(4/40}

5 mcg 17(5/30) 13(4/30) \4(4128)
There were no serious or a 1arm1 ng adverse

reactions attributable to vaccine.
ALT Elevations:
Two subjects who received 10 mcg doses of vaccine had
transient elevation of ALT (1.5 - 4.0 ti111es the upper
limit of normal) one to two months after the second
dose. Within one to two months of the elevations , the
ALT levels returned to normal. A reason for the ALT
elevations has not been discovered. The subjects have
not shown any clinical or serologic signs (HBsAg or
anti-HBt) of hepatitis B.
25481-3
1/18/86
Table 1
Antibody Responses Anuig HNlth Care f'ers.anm!1 Fo110ttlng Vaccination
trith 10 or 5 111:1 Doses of Yeast Aec:anl!llnant ff!patltls B YacclM
lots 8972/C--IC~ at o. 1. and 6 l'lonlhs In Study ~7M
't> wltlt Anti-Mis

... -·
1.0.
Q!IT fSll:II 1, e,I th Anti 419s
- . ·-
~
Clf'IT fS/t31
na12 All All
(ltnnths) Sln?:2.1 SIN?: 10 Vaccimies S/13?: 2.1 SIM ?: 10 . Sllll?:2.1 sm?: 10 \facclnns Sll:l?:2.1 S/13?: 10
u 29(11/38) 18(1/38) 2.3 15.2 35.J 31(9/29) 14(4/29) 2.1 8.9 33.3
2 83(29/35) 54(19/35) 16.4 28.7 75.5 74 (20/21) 48(1l/Z7) 8.4 n.2 31.9
31 19(26/33) 61(20/33) 11.1 3'S.8 73.6 79(23/29) 59(17/29) 12.6 23.8 ilO.S
6 89(32/~) 6!1(25/!S) 27.5 ~1.2 78.8 81(21/26) 69(18126) 14.2 N.2 35.3
1 91(35/~) 94(34/3'$) 160.8 185.4 209.3 84(21/25) 76(19/25) 54.0 113.4 152.t
!) 97(W3'5 94(33/35) 132. 7 152 .8 166.5 83(19/23) 78(18123) ~., !9.1 119.5
12 91(33/34) 91(33/34) 99.2 113.7 113.7 83(19/23) 78(18123) 44.5 ~-' 113.S
25481.....,
-
0
.0
.Q
1/18185
Table 2
PATitNT COUNT CLINICAL COt1PLAJtlTS
RECOHIIINAMT HEPATITIS 8 YACCIHt
STUDT t 17.,.
TRUTN!NT r
lOT NIJlfflER l CK•••
DOSE I 10 HCO
PATIENT ClA991 HEALnl CARE PERSONNEL
I TOTAL VACCIN!E9 ( 41 PATtflfTSI - DOSE I I

Il----------------------------------------------------------------------------1
DAYS POST VACClNATIOff I MlM!m
I1------------------------------------------------•-•-------------------------•
CLINICAL
C011PLAINT9 O I 1 I I I J • 4
.......................................................................................... • 5 I MITH .
•cOtlPLAINTS
..........•..........•.......... ,
REACTION, LOCAL IINJtCT. SITU I• 7 II 7 II 4 I• 2 I• ! I• l I• •I 10
I, 11.sY.1 I, 11.sY.1 • , 10.or.1 I, s.oio • c s.,x, I, z.sn • I, zs.01.1
-----------------------------------1----------
IHFUHl1ATJON I I ----------
O ----------
I ---------1----------
I I O ----------
I ---------- -----------
l
1.51.1 C O.OlO I 0.0?.J C 0.01.1 I I 0.01.1 I I.DiO I 1?.SlO
I
PAIN I I O O I • D O 1
l!,5i0 I 0.07.J I 0.01.1 I 0.01.J I C O.DXI I l,OJCI I l.51.1
SOIIENESS I 6 5 J I! I• t l 8
, is.01., c u.s;o , 1.s;r., , s.o;r., I , s.a;r., , 1.sn , 11.11:0
I
TEKDERNE99 I O l I O I I O 1
O.OlO I t.sr.1 I O.tlO I 0,07.J I C 0.07.J I 0,01.J I !,9Y.I
I
PRURtTJS CITCHlNOI I I l l O I D O 1
I C O,Oi'.I I I t.51.1 I I.Si!» I 1,07.I I I 0.01.l I 0.07.1 I I.SY.I
----------------·······------------1----------1----------I----------I-------
9TSTEHIC . I J I 2 I 1 I e
·--l----------l----------l----------l-----------
• l I 2 I • 7
I I 7.5)0 I ( s.e:o • I 1.s:o I I o.o:o • I l!.SlO • I 5.DY.I • • I 17.SY.J
~LE BODY/G!N!RAL
'II
J
7.51.1 C
1
t.51.1
'
1
2.51.1
'
I
o.o::n
'
l
I.S1.I I
1
1.s:o ( U.5l0
5
SMfATlkla
''' ' • O.Oi'.I
'
e
,.,1.,
'
l
1.s:u C
0
,.o:o C
0
0.01.1 I
0
O.OlO
'
1
1.51.1
fATICU£/MtAKN£99 'I 1 0 0 0
• 0 ' 1
nAlAl9E
'I ' 1.51.)
t
' I.DY.I
1
' ,.01.1
I
' 0.07.1
•
' 1.01.1
1
I 0,07.1
1
4.
4
!.SY.I
• 5.0i'.J
' t.51.J
' 1.51.J C
' r.s:o '
0.07.J 1.51.1 I 10.07.1 0
0
H!AOACHE
' C
0
O.OY.I C •
1.0lO
I
l,5Y.t C •
,.01.1 • • O,OlO
1
t.SY.1
N
' C O.OlO C 0
' 0
Table 2 (cont. )
PATIENT COUKT tlJHICAL CONPlAINTS
RECotffllHAITT NtPATIJIS 9 VACCINE
9T\IDT I 07~
TRtAfflENT
LOT NUtll'IIER a(tit,t,
OOSI: I HlttG
PATIENT CL.11991 NIEALTN CARE PEltSONN£L
I TOTAL VACCINtH I ... PATUtmn - DMIE I I

Il----------------------------------------------------------------------------1
DA TS P09T YACC I HA TIOM I NUffl!IElt
CLINICAL
COtfPlAIHT9
1--------------------------------------•-·-•---------------------------------I
8 0 I I I Z I S I t, I !I I NlTH
ltOfflllAtttH
a•a•~••••••••••••••••••••••••••••••l••••••••1tt1 •e•a••••• ••••••••••!••••••""•••••••••••••••••a••••••••••••••••••••••••
I I
tru!CUlOSl<IE Lll:TAL I O I I I O O ll 2
o.o,n I Z.SY.t C 0.01.1 I C 1.01.t ( O.OY.l I 2.!llO t !J.O?.t
I
HYALSIA I O O O I 0 0 1l l
D.0lO C O.OlO C t.07.1 I ( 0.07.t I D.07.1 I Z.51.1 I t.SY.t
I
rummITIS I o l o I o o o l
~ C O.DiO I l?.57.t I I.OY.I I C 0.07.1 I t.01.I C t,07.t I t.51.1
I
DI61!9TIVI! STSTEH I O O 1 I O O O l
O.OiO C 0.07.t I t.51.1 I C 0.01.:t ( 0,01.1 I t.07.1 C Z.SiO
I
ClAY-COlOl!IEO STOOLS I O O 1 I O O O 1
I , o.o:o c o.oxt c z.s:o I , 0.01.t , 1.07.t , 1.01.1 , t.sio
-----------------------------------1----------I----------I----------I----------I----------I---------I----------I-----------
PIER!llfflS NIVH CUNPt.AINT9 I 10 I t I 5 I Z I :S I J I I 16
I , n.o:o I c u.s1.1 I c u.s:o I c s.ox1 I , 1.sx, I c 1.s,;1 I I c o.o;o
-----------------------------------l---------l----------l----------l----------l----------l---------l----------l-----------
n1tscms MJnt NO CCffl'lA!NT9 I JO I U I 35 I 311 I J7 I J7 I I 24
I I 71.0)0 I I 77.17.t I I 07.57.) I I 95.0lO I I 91!.S-,O I I U.51.1 I I I 60.01.I
-----------------------------------l---------l---------l----------1----------1----------1----------l----------l-----------
l'tlf!IO!IS Mint HO DATA I I I I I 1 I 1 I l I 1 I I 1
I C , ••1.J I I z.•1.t I C l!.4'0 I I Z.41.t I I t.•:o I C z.•:o I I I 2.,7.J
0
0
IV
-
0
Table 2 (oont.)
PATIENT COUNT CLINICAL COHPLAINTS
RltotW!JNANT HlPATJ~IS 8 VAtCJHI'.
ST\JUY I 17.-
llfEATlffNT t
LOT t!UmEII
OOSE
: cic•••
: 10 l1CG
PATIENT tlAS9t HULTH CARE fttlfSOIMl
I TOTAL VACCINfES I •o PATIENTSI • DOSE Z I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I MUX3tlf
CLINICAL
COffl'lAIHT9
1----------------------------------------------------------------------------I
I O I l I t I J I 4 I 5 •
Wint
lttmPLAIHTS
DDDDa••••a•••a•••••••••••••••••1111•••••••••-••••••••••••l••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••a•aaaa
I I I • I • • I
l!IEACTIOH, lotAl IJN.JECT. SITU I 3 • 0 I O • D I I • 0 I I 3
I t 7.57.1 • t 0.11.1 I I 1.07.J I I o.07.J I I o.17.J I I 0.01.1 I I 1 7.!11.J
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sOREHUS I 2 • o I o I D I 1 • o I I r
• I s.o:r.1 • I 1.0,0 I c 0.17.1 • I 0.01.J • I 1.17.J • I 0.11.1 I I I !5.17.J
ttNDERN?SS
•I 1
I• I
II O
I• D I• I
•• I I• II l
I , r.s,o I c 0.1:r.1 I c o.o,n I , 1.0,0 • 1 e.a,o • , e.o,o I I 1 2.s,o
I • • I • I I I
ll'IIURITII I lTCHifflU I 1 I I I O • 0 • II I I I I 1
I c z.s,o I c o.oio I c 1.0,0 I c 0.11., I c t.111., I c t.01., I I I z.s:o
-----------------------------------1----------l----------t----------l----------l---------•----------l---------•-----------
svsmtrc I J I t • t I 1 • 1 • t I • 1
I I 7.!JlO I I J.OlO • I 5.07.J I ( t.SlO • I t.67.J I I J.JY.J D I I 17.SlO
t,/HOlt !OlJY/t:tHtRAL I :J
•
1
I
I
z.n,
l
t.57.) •
0.07.1
1
2.67.J 1
6
1s.a;n
t.51.1
' '
7.57.1 (
SN!ATING I 0 l 0 0 0 0 1
,.o:o ,.01., ,.01., t.57.1
' '·'"' '
t.07.) z.s:r., ( (
' '
FLUSff I
I c
0 l 0
0.07.)
D
0.01.,
D
1.0%1 • ,.o:o I
1
t.0)O Z.51.J
' • e.sr.1
( (
• ' '
I
FATH\Jt/NtAJtHESS I 1 I 1 0 2
I t t .57.) I 0.0)0 I Z.57.1 Z.SlO 1.07.J ,.01., J.01.1
I ' ' ' '
~lAISE
I• I
1 0
I
• I
0
11.07.)
II l t
Z,57.1 I
'·'"' t.67.J I . !11.07.I
( 0.01.1 0.07.I (
I
HEADACHE I
f
1
z.sio ( •
e.a,o I
0
0.07.1
I
t.0Y.I I
I
1,07.t I
II
9.17.1 I
1
Z,57.1
' I 0
INT[GU111:NTARY SYSTEH I •
9.07.I I
1
f.5)0 I
0
•••7.1 •
•••:in I
0
o.on I I
I •
,.01.1
•
l
2,57.1
0
f\J
' 0
"'
Table 2 (cont.)
PATIEHr COUNT CLINICAL COl1PLAINTS
REC0'18INANT NtPATIJIS 8 VACCINE
STUOT I 97'4
TR[ Affl!NT I
LOT ~18[1f I CK'l44
DOSE I 10 tltC
PATIENT ClAflt HUlnt CARE PERSONH!L
I TOTAL VACCIHtES I 40 PATIENTS! - DOSE I! I

1----------------------------------------------------------------------------1
I OAYS P09T VACCINATIOff I tM1MI!
CLINICAL l----------------------------------------------------------------------------1 MITH
CotlPLAINTS I O I l I I! I J I 4 I s I ltonPLAINTS
DaaoaDDDDDDDDaa••··············•IHl··········································•·u••··············•·D••········•·D•···········
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-----------------------------------1----------I----------I----------I---------I----------I----------I----------I-----------
PtRsOHS MITH COHPLAINB I • I t I t I 1 I 1 I t I I 10
I I 15.0Y.I I I 5.07.1 I I s .oi:1 I I t.51.J I t l! .61.1 I t 5 . J r.J I I I u .01. 1
-----------------------------------1----------1----------1----------1----------1----------I----------I----------I- .---------
PERS0t1S NUH NO COltPUINTS I 34 I J8 I 39 I Jt I J8 I J6 I I 311
I t es. 11.1 I I 95.07.1 I I n.oi:1 I t 97.51.t I t 97.41.1 I f '4,Tl.t I I t 1s.01.1
-----------------------------------•----------1----------1----------1---------1----------1----------1----------1-----------
ptRSOHS Mint HO DATA I I I I I O I O I l I I I I D 0
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IV
0
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Table 2 (ca1t.)
PATIENJ COUNT CLINICAL Cet1PLAINTS
RECOttBIHANT NEPATI T~S 8 VACCitfE
STUDT I 0794
Tl!EAl "ENT
LOT NUt18U! CK'144
00,( I 10 t1C9
PATIENT CLA!!ll MEALTN CARE PIR90NNEL
I TOTAL VACCIHtES I 4D PATIENJSt - DOSE 3 I

1I --------·---·-------·-·-------·-···-·-----·-·----·-·-·-·--······-------··-··1
. DAYS PO!lf VACCINATlOH I Hm&ER
CLINICAL
Cot11'UIHT9
1I ·-······-····--·•···••-·•-···-·-········---··-···-·•···-·-····-···-···-·-·-·1
O I l I f I 3 I 4 I !I I
Nll N
lt011PlAINT9
oaa•••••a•ooa•••••••••••••••••••a•a••••••••a•• ••••••••••••••••••••••••••••••••• •••••••••••••••••a••••la•••••••••laa••••••••
• I I I I I • I
RIEACTimt, LOCAL IINJIECT. SITU I a • J I Z I O I I I I I I t
I f ZO . OiO • I 7 . 57. t • f 5.07. t • I 0 . 07. t I I 1 . DXt I I t .o:o I I I ZZ. 57. t
··-·-·-·-·---·---·-----····-··-·-··•--------··
PAIN I 1
•-·-·-··-··•·······-·-l··-·--··--1
I l I O I O I
----------1
D I
·-········1········-·1·····--··-·
O I I Z
r . s ,o I I z.s::.o I I 1 . 0:r.1 I I 0 .07.t I t 0 .01. t I c 0 . 17. t I I c s. o7. t
SURt:NtS!I I 5
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-·····-······-·--·-···-·····-·-·-·-1I ··········1
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I t s.o:o I I z.s,o I I !1.17.t I I t .s:o I f 0. 01.t I c 0. 07. 1 I I f 10. 07. t
IOIOLE IBODT/Oftl(RAL I
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Tabl e 2 (cont.)
PATIENT COUfT CLINICAL COltPLAIHT5
IIECOt19INANT NEPATi fIS 9 YACCIH'f
5TUDY I 11,.
TIIEATtftNT :
LOT NIRfll[R I CK444
DOSI!". I 10 ttell
PATIENT CLAS51 11EALTH CARE PEIISCtMl
I TOTAL VACCINEES I ~I PATIENTSI - 005! J I

Il----------------------------------------------------------------------------1
DAYS POST VACCINATION I HU1111EA
CLINICAL
C011PlAllfTS I•------------•------------------------------------------------•--•-----------1
I I l I I! I J I • I 5 I
~ITN
ICOHPLAlNT!I
••••~••••••••••••••••••••••••••••••••..•••••••••••••••••••••••••••••••••••••••••n•••••••l••••••••••l••••••n••I••••••••••
• I • I • I I I
DIGUTIYI!". ST9TEH • 0 • 0 I I! I 1 I t I o I I I!
I I , .01.1 • I ,.o;o • I 5 .01. 1 I I l! , SiO • I 0 .01. 1 I I 0 . 01.1 I I I 5 . l iO
I • I • • I I I
LOOSE !ITOOl • II I O I l I I I O I O I • l
I I 1 .0lO • I 1 ,11. I I I 1! .57! 1 I I I . I i'- ) • I 1 .01. 1 I C l, Oi'-1 I I C l! .SY.I
CLAY·COLOIIED STOOLS I• O
II O
II l
•I l
II O
I• I
•I •• l
I I 0. 01. 1 • C 1 .0,0 I C 1!. 5)0 I C Z.SY. I I C 0 .01. 1 I C t. llO I • c l! .SY.I
-----------------------------------1• ----------l----------1----------1----------1
P£Rs111,s ~ IT11 COffl'lAINTS 9 • J • ti I 1 I
----------1
O •
----------1----------
11 •
I-----------
I JO
I I !Z. SY.I I I 7,SY. l I I 11 . I XI I I l! .51. 1 I I O.OlO I C 0, 17!1 I I C U.OY. I
-----------------------------------•----------•----------1
PtRSOt!S e.lllH NU CUffl'lAINTS I Jl I J7 I----------1----------1
36 I 39 I----------I----------I----------
•• I •o I I-----------
I JO
I t 77,5Y.I I C 92.57. 1 I C 91. 17! 1 I I 97.57. 1 I 1100.01.:1 I UH.Oif.l I I C 75.0Y.I
----------------------------- ·-----•----------1
P(IISl»IS e.!l TH MO DATA I O I ----------1
O I ----------1
O I ----------1
I I ---------1
I I ----------1
I I ----------1I -----------
0
I t O.OY. I I C 11 . I Y. I I C 11 . IIY. I I I , .01.1 I C 0.0:r.1 I C 1 . 11. 1 I I C , .ein
0
0
IV
0
VI
Table 3
PATIENT COUNT NAXl~ TlHPIWATUIRf:9
Rf:Cot181NANT" HlPATJTIS 8 VACCINl
ST\JDT I 079"
Tl!EAT'1£NT
LOT tlUtll!Ut Ck444
DOSE ! 10 NCO
PATIENT ClA991 MtAlTM CAR! PIEASOtlNEl
I TOTAL VACCINllS I 41 PATIEHTSI - 009£ 1 I

1I ---------------------------------------------------------------------------------------
OATS POST VACCIHATlmt Il NU1111£R
MX TEHP~AT\JRE
IOEG F, ORALI
l---------------------------------------------------------------------------------------1
• O • 1 I I • J I ~ I 5 I I I NAXNITff
TEltP
••••••••••••••••••••••••••••••..••••••••••••••l••••••••••••..•••••••l•••••••••••••••••••••l•••••b••••l••••••••••l•••a•••aae
NOll11AL I 5 I 6 6 I 6 I 6 I 6 I I 5
•
U.5,0 • I 16.71.J • r 16.fl': I • I 16.27.1 I I 16 .71.l I I H .1!7. 1 I I I 12.SiO
I I I I I
I•
<fl I 30
75.07.l •I• t t9 JO ]I
I I 81 . 1%1 I I 11 .uo
80 .61. ) • •I I 29 Z7
• I
I I 81.87.1 I
80 .67.1
I 27
I I 17,57.)
I I I I I I
" - "·' I 5 I l I I I l')• I 1 I 0
I 1 1.e;o I 1 o.or., I
I I
I
1
U.57.1 • I t.87.1 • I 1 . n 1 I 1 0.0,:1 I 17.57.1
iao - 100. , I • I o I o I 1 I o I o I I 1
I I o.or.1 I c 0.07.1 • c o.o:o I I 1 .77.1 I c 0.0:r.1 I 1 0. 0:r. 1 I I I 1 .s;o
------------------------1----------1----------1----------1----------l----------1----------•---------------------l-----------
vtHPtRAT\JlfE VMEH I 40 I 36 I J7 I J7 I J6 I n I I 40
I I 97,6U OI 8 7.87.1 I I to . I T.I I C 90.17.1 I I 8 7.8'0 I I 00.51.t I I I 97.67.I
------------------------l----------l---------l----------•---------l----------l----------l---------------------l-----------
nNl'E11AT\Jlf!: MOT tAltEN I 1 I , I 4 I 4 I s t • I I 1
I I l . 4 XI I I u . 1:r. 1 I C 9.Ht I I 9 . 87.t I I 11.11.1 I t u .s:u I I I 1 .4XI
0
Q
IV
0
a-
Table 3 (cont. ►
PATIENT CO\IKT NAXJ..wt TENP£1tAT\JRES
ltECDt181HAKT HEPATI TIS 8 VACCINE
Sl\JQT I t l',..
l ltEAfflEflT I
LOT tM1l!t lt I Clt'14~
DOSI! I 10 t1C9
PATIENT ClA9S I HEAllM CAltt PEl t ~L
• TOlAl VAtCINEES I 48 PATIENTS) - 00,1 2 I

l---------------------------------------------------------------------------------------1
I DAT9 ~T VACCINATION I NUNBEA
t1AX Tf~l'tRAllJIIE
I DH f', OffAll
•--------------------------------•-----------------------------------------------------1
• 8 • I • ! I J • ~ • S • • I HAI<Mint
Urtl'
•••••••••••••••••••••••••••s••••••••••••••..••••••••••••••••••••••••••••••••••••••••••••••••••••.. ••• • ••••••••••••a••••••a ■
NIJlfflAL
•I 5
II 5 •
I 5 •
•I • s • • 6 I • • I• 5
I I l! .51. ) I I lJ . 5 )0 I I 1J.9X ) I I U .SiO • l l!ll .tlO • C 17.6XI • • I l!. SXI
. . . . . .
I I • • • I I I
< 99
n - 99.9
.
I
I
I
• C
n
C 8 0.0X J
J
7.s:u
'
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I
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l
t .no I
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1
•
t .e:n I
I
Jl
l
I
C ! ,7X) • I
I
H I
t
t6
•
I
C IIJ . 8 Y.I I C 8 J .JY.I I C 81 . lll! I I l 78 . lliO I C 76.SY.J I
t
6 . l XI • C 5 .91.I
I
1,
•
I C
I
I
f9
72.SX )
6
C H . Ol!)
------------------------
TElff'ERAl ~E TAKEN I•----------1
4t I ----------•----------
J l' I J6 I1----------1----------1
J7 I JJ I ----------1---------------------1
34 I I -----------
40
I U00.07. l I l 92 , 5)0 • C 90.0iO I I 92, 57. l • l 92.SY. I • C 115.0X I • I U OO,OX I
------------------------•----------•----------1
TetW'tltATUIIE KUT TAKffl I t I J I ----------•----------1----------1
4 , I J I 7 I ----------•---------------------1
6 I I -----------
o
I C 0 , 81.J 8 I 7. 9XI I C J O.OT.I I I l', SY. I I I 17. 9XI I C H ,OY.I I I l 0 . 01.I
0
0
rv
0
-.a
Tabl e 3 {coot.)
PATIENT CotMT tfAXl rtJlt TENPERAl\JRES
RtCotlBlMINT HEPATi lI9 B VACCI N!
ST\JUT I 0 7M
11fUntt:NT
l OT NUll&f:lf I Ck4"'°'
DOS( I 10 t1CG
PAT IENT CLASS• HEALTH CAIi! PP!ONN!l
I TOTAL YACCIN£t9 C 40 PATUHTS, - VOSE J I

•---------------------------------------------------------------------------------------1
• DAYS l'OST VACCI NATIOff • Htlffll!R
NAX TE"PERATU!tt
CDEG F , OltAU
1
•
-----------------------------------------
0 I l I Z • J
. --------------------------------------------1
I 4 I !S I I
MI TH
I HA)( l(HP
anwnaw•awa••••••••att••••••••••••u•f••••••••••l••••••••••l••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••a
• •
NOIINAt I • I a II a I
•
•
•
I •
•
• •
•
I
I
• e
I I H . 01. ) • I H . !11.1 I C U .6lel I I 11.UO I f U . 1:r.1 • I H . !IXI I • I H . 07. 1
I I I • I I I I
< 99 I 30 I n I HI 29 I HI Jo • I 26
• I 75. 0U I I 74.4l0 I I 70 .37. ) • I 76 , 31.1 • f 7J .7Y.I • f 76. 9%1 • • I (t!l.117. 1
I I • I I I • I
9" - 99 , 9 • I? • I I J I l • I I l • I 6
I C !J.OY. ) I C 11 . 17. 1 I I 8 . l lO I C t.6l0 I C J .J)!J I C Z,6:t) I • I l!J .O,O
------------------------1---------1
TElff'flfATURt TAKEN • 4t I ----------l----------l----------•----------1
I
J9 I
1100.tY. J
37
I
31 I JI
C 97. 57. J • C 9Z.5%J
I
I ----------•·--·-----------------•-----------
J9 •
I .s. o:r. 1 I
I
C 95. t Y.I
40
I I 97 . 51. J I I 11111 .07. 1
------------------------ I•----------•----------1
UftnRAT\JRE NUT TAKEN • I l I ----------1
J •
----------1----------1----------1
z • z I l I ---------------------1
I -----------
•
I I O, I XJ I I Z, 57. 1 I I 7 ,J iO I C 5 .0>: I I I 5 . 01. I I f Z. 51. J I I C e.o;o
0
0
l'\J
0
0:
Table 4
PATltNT COUKT CLINICAL COl1PLAINTS
RECOl18IH.AHT KEPATIT49 8 VACCINE
91\JDT I 07'M
1Rl!AmtNT I
LOT H\Jtft!ER I Ck"44
005( I 5 11C&
PATl!HT tlA!ISI HtAlnl CARt Ptw!lotML
I TOTAL VACClftttS I 30 PATltNT9t - DOSE l I

l---------------------------------------------------------------------------1
I DAYS POSf VACCIHATIOM I H\JfflSER
CllHICAl
CffltPUtH1t!I
1
I ----------------------------------------------------------------------------•
o I 1 I ! I 1 I " I s • MITH
•c0!1PUINTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••I•••••••••••••••••••••
I • I • • I I I
REACTION, LctAl !INJECT. SITEt • 4 I 1 I l I I I o I II I 4
• I 13.'JY.t • I J,3l0 I C 3. 3Y.I I C O.OiO I I 0 ,01.1 • C 1 .01.1 I • C 13,31.D
-----------------------------------1
PIIIH I ----------
l ----------
O ----------•----------•---------
t I t I O ----------
O ---------- -----------
l
I I 3, 3Y.J I 0 .01. 1 C O.OY. I I f O.OlO • C I .o:o I 1 .01.1 I J.JY.I
I I I
SOl!ENlSS I t 1 1 I • I o o 3
I I 6,T/.1 I l ,3l0 I 3 .lln I I 0.01.t I I 0 ,07.I C 0,07.l c 10. 01.1
• I I
EIIYlH!t111 ll'ltDN!S9 I I l O O I t I O t l
I I l ,lY.D I t , 01. J I O.OY. I • I t.tlO I I t ,021 I 0.07.1 I 3 , 31. J
I 1. I
SllFFHt:!19/TtGIITNf:fl I 1 o I I • I o • 1
I I J,3l0 I 0 .01., I C,,OY.I I I o.oin I I 1 .07. 1 I o.o;o C 3,3i0
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
SYSTEHIC I l I I I l I D I 3 I I • I J
I I 3.37.I I c 6,7l!I I I J,J?.t • I 0.0lO I I 10.3:r.l I I , ••,n I D C 16.7i!t
NNOlt BODT/GtNtRAl I I 1
C
l
lJ. J?.I I• (
l
3.3?.J (
l
J, 3Y.I I o.o,n
J
C l0,J7.I ( 3.47.1 "
I 13,37.D
I
SUl!IATifflf Of' NAlflfflf, 8ENHAl I 0 I 0 l 0 a I I
I I Cl.DY.I I ( 1 .0:r.1 ( 3.31.1 C o.o,n ( o.o:u C O.lllO C 3.JY.I
I
FA TIGU!A!UIOft!l!l •II I 1 I l
3, :JY. J I I S.JY. I
II
O.OY. I •
O. Ol!t
Cl Cl
1,01.1
I!
I I I 0.01.1 ( I A.7Y.J
I I
HA LAI!IE
I• I
o
o.o:u
I
I I
0
, .01. , I
'l
3, 3Y. I I •
O.tiO I
I
6.9:0
I
,.01.1
e
I . 5,7Y.I
Hl!:ADACK!t
I
I o
I
I • • II ll
' • 1
1 .0:r., I t O,OX J I 11 , I Y. 1 I 0 , 0iO I J,4XJ 11.0:0 I ].JlO
STSTEHIC INFECTION I 0
I
I • • •, l
' 1 1
0
0
rv
O.OY.J I I 0 .01.J I O. OY.I I o.ox I :s.~1.J I 3.47.1 :!l.3i0
' 0
,0
Table 4 (cont.)
PATIEKf CotMT CLINICAL cot1PUIHtS
RECot191HANI' HEPATlT~S 9 VACCINE
!lnlOY I 07~
TREATH£HT •
LOT NUIIBE" I CK~44
00SE r S HCG
PATIENT CLASSI HEALTif CME PERSONN!L
f TOTAL VACCINEES I JO PATJEHT91 - DOSE l I

1----------------------------------------------------------------------------•
f DAYS l'O!IT VACCnfATION f NUl18ER
CLINICAL
COIIPLA1tff9 1-------------------------------------------------·--------------------------I
I O I 1 • ! I J I 4 • 5 I WITH
•c01PUJHT9
•••••••••••••••••••••••••••••••••••!•••••••••••••••a••••••••••••••••••••••••••••••••••••••••••••• aaaa•••••• ••••aaaaaa
I I
IIESPIR ATCRT I 0 1 0 o O I O 1
0.07.I ( J.]Y.I C 8 .07.1 I O.Ol!I I o.ol!, I f , .o:o I J.3)(1
I
UPPER RESPIRATOltY INFECT., tm I O 1 O t O • 0 1
O.Ol!I f J.];O f D. 07.1 I t .Ol!I f 11. 01. 1 I t t.07.I C J .'Jl!I
I
DIGESTIVE SYSTIEn I O O O t O I 1 l
0.07.1 I 1 .07. t I O.OlO t t .117.1 I 0.01.1 I I J .4l!I I J.lY.I
I
A800!1IHAL ll'AIIB/1:RAHP9 • 0 0 0 0 0 I l l
f t O.Ol!I t O.llO t II.ox, t O.Ol!I • I 9 .0)!1 f t J .47.I I J.31.1
-----------------------------------•----------1----------•----------•---------•----------1----------•----------1
PEIISOOS NITlt cottPLAIMTS I 5 I J t t I O I J I t I I -----------
a
I c 16.77.1 I < 10.oxt I < 6.1;0 I t e.1Y.1 I c 10.:,,0 I t •·"" I I c H.1:0
-----------------------------------1I ----------1
PEASOMS MITH NO Cllt1PUINTS 25 I
----------1
t7 I
----------1
ta I
----------1
!9 I
----------1
H I
----------1----------1
t7 I I
-----------
ZZ
I t e1. 1Y.1 I I to.HJ • t •J.JY.I I not .ex, I c ••· 7lo I c H . uo I I • n.1:0
-----------------------------------
,r"!ICIM9 MITH m, IJlU Il----------l----------1--·-------l----------l----------l----------l----------
o I o I I I l I l I l I Il-----------
o
f t O.OY.I I I 0,07. J I I t .o:o I I J.JXJ I I J .JXJ I t J.JlO I I t I .IY. J
0
0
-
l'V
0
Table 4 (cont.)
PATI£Nr COUNT CLIHICAL CONPLAJNTS
RECOtt8l1WIT HtPATlll_!I II VACCIHE
STUOT ! 07~
TREATltENT l
LOT NUl18EII I Cll.44~
DOSE I 5 11CG
PATIENT CLA99 • HEALTH CARE PEllsotML
I TOTAL VACCINEES I JO PATIENT91 - DOSE! I

1----------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I NUlt8EA
CLINICAL
CDl1PLAINT9
1----------------------------------------------------------------------------I
I O I l I t I J I ~ I 5 I MITH
ICOl1PlAIHTS
••a•••••••••aaa••••••••••••••••••••l••••••••••l•••••••••••••a•••••••l••••••••••l••••••••••l•••a••••••la•••••••••I••••••••••
I I I I I I I I
1tucn0H, LutAL I mJEtT. snu I 1 I z I 1 I , I o I e I I :s
I I J.3?.J I I 6.71.1 I I J.3?.I I I 0.07.t I I 1.0:0 I I o.er., I I I 11,81.1
-----------------------------------1----------l----------•----------l----------l----------l----------l----------l------·----
PAIH I O I 1 • t. I I I t I O I I 1
I I 0.07.J I I J.11.1 I I 0.01., I I 0.07.1 I C ,.01.1 I I 0 .01.J I I I J.J7.I
I I I I I I I I
!90ltEHESS ( 1 I 1 I I I O I t I I I I 2
I c J.1r., I , ,.,r., I 1 1.1:1., I I o.ou I 1 ,.or., I , o.or.1 I I , ,.,r.1
-----------------------------------1---------·l·---------l------·---l---·-·----l----------l---------l----------l-----------
s,s1en1c I l I 1 I J I o I o I 1 I I ~
I I 10,07.1 I I J.J7.I I I 10.07.I I I 0.01.1 I a o.oi!J I I J.Jr.J I I I lJ.31.1
l!HOlE BOOTIGEHtllAL I l 1 I 0 0 I I I J
11.0i!J I J.Ji!I I J.JlO I o.o:o I t.17.1 I I J.s,o I I H.ti!I
I I
CHILLS I 1 0 0 0 D I 1 I 1
I s.n, I 0.0)0 I o.o:o I 0.01.I I O.OXJ I I J.Ji!J I I J.31.1
I I
nALAISE I
I I
l
J. 11.1 I
0
o.or., I
1
J.37.l I
0
l .0%J I •
I. OY.J
I
I I
I I
, . , 1., I I
t
•.no
I I
KEADtlCHt I z
6.r,., I
I
J.37.1 I •
,.01.1 I
0
0.07.1
0
I .Oi!J
I
I I
II
e.er., ,.n,
t
'
(
l'IU9CUt.09U LIET IIL I 0

1.01., I •
I.OU I
1
J.JY.I I
0
O.OY.J I
0
1.01., I •
1 .01., I
1
J.)7.1
AXILLARY ~EA 9«1R! I 0 0 1 0 0 e 1

I I
I
0.01., I o.o:u • J .JY.I I 0.01., I 0.9'0 I 1 .17.J I J.JY.I
e z
'
Ul&HTJVI! ST!ITEl1 0 1 1 0 G
I I o.o:o I J.37.1 t J.3)0 ,I I 0.07.1 C 0.17.) I o.o;o C 6 .77.1
I I 0
Dltll!RHl!A I • II 1 I 0
' • 1
--"'
0
II O.IIY.I I 1.0:r.,
• J,3Y.I I I O.HI C o.,:r., t ,.a:r., I 3.3l0
Table 4 (ex>nt.)
rATIENf COUNT CLINICAL COHPLAINT!I
RECCJt1lllHANT fflPATl! l!I 8 VAtCIHE
STUDY I 0194
TRO Tl1£HT t
LOT tMIBER I Clt44•
DOSE I 5 t1C9
r AT J(NT CLA99 t HEALTH CARE PER90t0lEL
I TOTAL YACCI NEE9 C 30 PATIENT9 1 - ·nosr ! I

1I ----------------------------------------------------------------------------I
DAY!I PO!IT YACCIHATIOH I Nlffl!IER
CLJHlCAL
COffl'L AJHTS
1I----------------------------------------------------------------------------
O I l I t I J I Ii I 5 I I MITH
ltONPLAlNT!I
••••••••••••••••••••••••••n•et1••--••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l••1ttt••••••
NAUSEA
•• 0
•I 1 II O II 9 II O II 9 II II l
I c o.on I c J .J1.1 I 1 0. 01. , I • 0 .01.1 I c ,. o:o I , 0 .01. 1 I I c 3 . 1;0
------·----------------------------1
PER!ION!I Mint CONPU INT9 I ----------
J I•----------1
2 I ----------•----------1----------1----------1----------1-----------
4 I I I O I 1 • • 5
I ( 10 .07. I I ( 6 .71. 1 I I 13.31. 1 I I 0.01.I • ( O.OY.I I I J .l)( I • • I 16.7:0
-----------------------------------1
PEll!IOIIS MITH HO tot1PLAI NT9 I ----------
t7 I•----------
H •----------
• t6 I•----------1
30 I ----------1----------•----------1-----------
30 I t9 I I !!5
I I ,o.o:r., f ( 9 J.JY. I I I 86.7Y. I I n oo.11. 1 I n oo.o;o I I '6 .T/. 1 I I I 83 .Jif.J
-----------------------------------1----------1----------1
PER!IOtfS eon H HO oar~ I o I e I ----------
o It----------•----------1----------1
o I o I , I ----------1-----------
I o
I I 0 .17. 1 I I 1 , 117. 1 I I 0 . 01. 1 I t a.ox, I I O.OXI I I 0 . 1;0 I I C o. o;o
...
0
IV
"'
Table 4 (cont.)
PATIENT COUNT CLINICAL CIJfflllAINTS
RECotl8INAHT HEPATITIS 8 VACCIN£
STUOT I 07 ..
TREATNtNT l
lOT N\RtBER I CK44(1
DOSE I 5 HCG
PATIENT CLASS: ffEAlTII CARE PEll!IOl'ML
I TOTAL VACCIHEES t 28 PATIENYSt - 003! 3 I

1-----------------······-·----···-·-····---··-··------·-····----··---··-····-1
• DAYS POST VACCINATION I tM'l8EII
CLINICAL •··--··--•·--·-. ··--•····---------•·----···--·--------···-·-···-•········-···1 WITK
COl1PLAINT9 • 0 • 1 I E I 3 • t, • 5 I •tOHl'lAJNTS
oo•••••••••••••••••••••••••••••n••••••••••••••••••••••••l•••••••••••••••••••••••••••••••••••••••••••I•••••••••••••••••••••
• I I I I • • I
RUCTION, LOCAL !INJECT. SITU • l I 3 I l I O I O I 8 I I 4
I I J.67.J • f 10.77.J I I J,67.J I I O,D7.1 I I 0.07.1 I I 0.07.1 • • I 14.37.J
·-·······-····-·-·--···----·---·-··•·····-·-·-1··--······•··········•··········1··-·---··•-··-·---·-1---·---·--•··-----··--
SOl!tH!99 • l I J I l • · I I t I II I I 4
I I J.6r.J I I U.7XJ I I J.6Y.J • I 0,17.I • f 0.07.J • f ,.ex, I I f lll.J7.J
-·----------------··-·-·-·--------1··----·---1--·-----·-1----·---·-•--·····---•·····-·---1··········1··--······1······-····
STSTtHIC • t • 3 I l ·I I I 1 I e • I Ii
I I 7,17.1 • f 10.T/.I I I J,6l0 • I 1.117.J I I J,67.1 I C 0,11.1 I I I lft.37.J
------------
NIIOU 80UY/CtNtllAl • t
C 7.1)0 f
3
u.r.o I
l
J.6Y.J I
O
0.17.J
l
C 3.6)0 C
I
o.ox,
'•I ft
I 14.37.J
I
FATIGUUMtAKtltS9 • 0 1 l I l II I 1
t.o:o I J.6Y.J I J.6Y.J C o.o:u I J.6l0 I 0.07.J I I J.67.J
I
HAlAIS£ I I ! 0 0 II II I f
1.07.t C 7.U!I I O.OY.t I 0.117.1 C 1.07.1 C O,O;(J I I 7.UO
I
HEADACHE I l I I O e I f l
3.6'!1 I 0.11.t I 0.07.J f 0.07.1 I 0.11.t C o.ax, f I J.67.t
I
S&IOUEH ANltlts I 1 l 0 9 I 0 I l
J.6'0 I J.6'0 I O.OU f l.liO I 0.17.) I 0,07.J I• lJ,67.J
. . I
H£1!YOU9STSTEH • l Cl O I O I I I
J.6xt I 0.07.t I O.IXt I 1.17.1 I 0.07.t I 0.07.J I I J.67.1
I
vtRTIGOIDIUINt:SS I l O I I O O I 1
• I J,6XJ I a.ax, I o.tn I •• ,7.1 C o.o;o C O.OY.t I '· 3.67.t
----·-----··-··-···-··--··--··-····•·······--·•-···-···-·1··--·-··-·1·------·--•---·------1······--·-•-·---···--1-----·----·
PEIISON9 Nllff tCIHPLAINTS • t I 6 I t • 0 I l I t . I 7
• c 1.1Y.1 I c n.11Y.1 I c 1.1n I c o.oi:, I c J.67.J I c o.or.1 I I I rs.ox,
-------·--·····-··---··--·-·····-·-•····--·--·•···-·--·-·1---·------1-·--------1·---·--·-·1·---------1----------1-----------
,EflSONS NITif NO COttPLAINT9 I 26 I U I ti • 28 I t7 I 28 I I n 0
0
I C 92.9l0 I C 71.67.1 • I U.9llt I Cllt.07.t I I 96.4:CJ I 1100,17.J • I I 75.DY.I
-"'
\l>I
Table 4 (cont. )
PATIENT COUNT CllN?CAl CottPLAINTS
RECOf18IHAHT HEPATITI.S 8 YACCltff:
!IT\RJY I 07~
TRl:A Tlff:NT
LOT NUNBEII tK444
OOSE g t1CG
PATIENT ClASSI HEALTH CARE PEll!llt&lll
I TOTAL VAtCINEES I re PATIENrS) - DOS! J I

1I ---------------------------------------------------------------------------I
OATS POST VACCINATIOH I IUtB(R
CLINICAL
ClltlPLAIHT9
1I ---------------------------------------------------------------------------
I I 1 I ! I J • • I 5 •
IIC011PlAINTS
NITff
•a••••••••••••••••••••••••••••••••• l•••••••••••••••••••••••••••••••• l•••••••e•••••••••••••l••••••••••l••••••••••I••••••••••
----------------------------------1----------1
I I ----------1----------1----------1----------1---------1
I o I e I I I ----------1I -----------
PEll!IOH! ~Int NU DATA
I I
O
O.OY.D I I
t
, .,.,., I C o.o;n I I
O
, . 01., I I
O
0 .01. , I C • • ,1., IG
I I e.o;o
0
0
....t::
N
Table 5
PATIENT CO\INT NAXItlUl'I TEffl'ERATURf9
RtCUXIIINANT H(PATI~I9 9 VACCINE
snun , 01~
TREATtmn' I
LOT NUXBER t C"4'4
OOSE IS NCC
PATIENT ClASSt ltEALTIO CARE PlR9CWl£L
I TOTAL VACClNEES C JI PATIENTS I - DOS£ l I

1--------------------------------------------------------------------------------------I
I DAYS POST 1/ACCIHAllmt I NtmBtR
NAX TEHl'!RATUIE
COEC F, Ol!All
1--------------------------------------------------------------------------------------I
I I I l I ! I J I 4 I !J I I I HAXMITH
TEltP
a•••••••••••••••••••••••l••ttt1••••••
I
••••••••n •••••••••• •••••••••• ••••••••••!•••••••••• •••eaa•••I•••••••••• ••••••••••
I
NORHAL I 1 l l l 1 I l I
J.JY.l C J.JY.I C J.4l!J I J.61.1 I J.6Y.I I I J.4l0 I 3.31.J
I
< 99 I t!J 24 26 24 u I 24 11
H.3Y.I I 81.DlO I 99. 7Y.I I 85. 71.1 I 78.6Y.I I I 92.8l!I I H.11.1
I
" - 99., I 4 s z t it I 4 u
n.JlO I u.nl I 6.97.1 I 7.17.1 I ll.7.9Y.t I I n.11;0 ( 36.71.1
I
!110 - 100., I t • o 1 t I o 1
I • o.oY., I , e.eio c o.oio c J.6lo I I e.0,:1 I 1 ,.01.1 , J.37.1
------------------------l----------1----------l----------1----------I----------I----------I---------------------I-----------
TENP£RATU11E TAIIEH I :,o I JI I Z9 I 29 I 29 I 29 I I :,o
I 111t.01.1 I n1t.01., I c 96.n, I c n.11.1 I c n.:,,;1 I t 96.77.1 I I cuo.ou
------------------------1----------1
TEffl'EIIATUIIE Oll>T TAKIEN I o I ----------l----------l----------l----------1--·---I--------------------I-----------
• I 1 I e I e I 1 I I •
I I 0.9%) I C 9.DlO I I J.JXI I I 6.7l0 I I 6.7''.I I I J.Jl(I I I I O.OlO
0
0
-
N
1/'1
Table 5 (cont.)
PATIENT COUff NAXItMI TU1Pf1tAT\JlfES
IIECOt181HAN1' ffEPATITJS 9 YACCltlt'.
STUDT I 117~
TREA ffl9fT I
LOT NUtlBER I CK4'4
DOSE t S HCC
PATIENT tLASSI ME ALTM CME PERSOffNEl
I TOTAL YACtINEES t 30 PATIENTS) - OOS( I I

1I ---------------------------------------------------------------------------------------
DAYS l'09T VACC INATION II IU1BEII
l'IAX 1Et1PEIIAT\IRE
I DEC F, OIIALJ
1I ---------------------------------------------------------------------------------------
I I 1 I I I J I It I !J • •
•• "AKNllH
TEHP
aaa•••a•••••••••••••••n•••••••••••••••••••••••••••••••n••..••••••••••••••••••••••••••••••••••••••••l•••••••••••••aaaaaaaa
~t1Al I I t I I I t I t I I I I I
• 6. 7l0 I t 6.71.1 I t 6.T/.1 I I 7.11.1 I I 6.71.1 I I 6. 11. 1 I
II '
6.T/.l
I I I I
I 14 I 14 I 14 • 24 17
• I• t6 I 19
< "
I I eo .o,o I •
t 81.111.l I l II0 .111.I I I 85 .77.1 I I fl.e ,i:1 I I 96,71.1 I •I l 63.37.l
I I I I I I I
.,., - I I t
I
"·' "
u.:s,o I I
I
•• 77.1
I
I l " I
lJ.37.1 I l
I
7.11.J
I
I l
1 I
3.J7.t I t
I
• · 77. 1 I
I
I {
1
U.37.t
100 - 100.'I I e I I o I o • I o I • I
I , , .on I •
!
•.11.1 I I o.o,o I • e.01.1 I t
1
0.11.1 I , , .o,o I I • •.n:,
------------------------1I ----------1----------1
TEt1PERAT\llll! TAKEN 30 I 311 I
----------1-------
JO I f8
·--1----------1----------1
I ,0 I :so I ---------------------1
I
-----------
:so
I 1109.0lO I uoo.o,o I 1100.01.1 I ( '3.J1.I I U Ol .llO I U00,01.I I I {100.1 1.I
------------------------1----------1
T!ffl'(RAT\m( t101 TAUH I • I
----------1
• I
----------1
e I
----------1----------1----------1
I I e I o •
-------------------- 1I -----------
•
• t o.o:io I t 11 .ex, I t , .ox, I c 6.r.o I c 1.1x1 • t 1.0?. 1 I I t o,o:o
0
0
-
N
0-
Table 5 (cont. I
PATIENT ClllMT 11AXl,-Jtt TEHP(RATURES
RECOt18IHANT ffEPATIT,s 8 VACCINE
Sl\/DY I 0794
TREA111£HT
l OT NUffllER I CK~""
DO,£ I 5 ffl:8
PATIENT ClA9St HUlTII CAIi£ l'tRSOt-lNtl
I TOTAl YACCINIE!S ( f8 PAYIENTSI - DO!E] I

1---------------------------------------------------------------------------------------I
I DAYS POST YACCINATIOH I HUtte!R
HAX T£ffl'£RATUIIE
I DEG F, ORAi.i
1I---------------------------------------------------------------------------------------l
O I 1 I 2 I J I " I 5 I I I tt!IXMITH
TEttP
aaQaa•••a•••••••••••••••l••••••••••l
I I
..••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
I I I I I I
tromAL I " I " I 4 I " I 4 I " I I ,
I 1 1, .11. 1 I c 1,.31.1 I 1 14.81.1 I c H.Jio I a H .11.1 I c 1ti.J1. 1 I I r 1,.11. ,
I I I I I I I I
< . 99 I H I 21 I U I 21 I U I t! I I 19
I c n.ti1.I I c 75.0Y.I I c 77.87. 1 I I 75.81.1 I f 11.01.1 I c 78.6l0 I I c 67.9Y.I
I I I I I I I I
99 - 99., I " I l I r I l I l I r I I s
I c 14 .11. , I c 10.11.1 I c 1.•1.1 I c 10.no I c 10.n, I c 1.1:r., I I t 11.,x1
------------------------1----------1
TU1PHATUIIE TAKEN I H I ----------1----------1----------1----------1
ta I t7 I ts I H I ----------1
a I ---------------------1-----------
I za
I cuo.or.t I 1110.07.1 I c '6.•:o I uoo.07., I uoo.01., I uoe.01., I I n oo . 11Y.1
------------------------1---------1----------1----------1----------1----------1----------1---------------------1-----------
TftW'ERln\JWt: HOT TAKEN I O I O I l I O I O I O I I I
I f • • • ,o I t o.ox, I C 3 •• ,n I I ,. oie, I C e.o,o I C e.o,o I I t 0 .8)( 1
0
0
-.....
IV
STUDY 795
00218
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepat\tis B Vaccine,

Study 795

recombinant hepatitis 8 vaccine by health care
personnel and other healthy adults negative for
hepatitis B serologic markers.

Lot #934/C-J625 (lOmcg HBsAg/ml)
Lot #979/C-K564 (lOmcg HBsAg/ml)
Lot #81990 0/18066/C-L215 (10 mcg HBsAg/0.5 ml)
PRINCIPAL Prof. Or. Friedrich Deinhardt

INVESTIGATOR: Max v. Pettenkofer lnstitut
8000 Muenchen 2
WEST GERMANY
SECONDARY Dr. W. Jilg

INVESTIGATORS: Dr. R. Zachoval
Dr. G. Zoulek
Dr. M. Kroner
Or. J. Abb
Dr. B. Lorbeer
The above secondary investigators have the same
address as the principal investigator.
Dr. u. Bienzle
Ansbacherstr. 5
D-1000 Berlin 30
WEST GERMANY
STUDY LOCATIONS: nax v. Pettenkofer lnstitut

8000 Muenchen 9a
WEST GERMANY
Ansbacherstr. 5
0-1000 Berlin 30
WEST GERMANY
23841/1
1/3/86
Study 795
DATE COMPLETED: I~ progress.

health care personnel and other healthy adults of
·negative for HBsAg, anti-HBc and anti-HBs, have a
normal ALT level and have not previously received any
hepatitis B vaccine.
STUOY PROCEDURE: Eligible participants receive a 70 mcg intramuscular

injection of vaccine produced by the inmune affinity
or (15)(4) procedure at 0, l, and 6 months.
Vaccine reclp1ents are asked to record their
temperature daily for five days after each injection
of vaccine and also to record any local or systemic
complaints that they may have during this period.
A blood specimen (10-15 ml) was obtained fr0111 each

vaccination and on the day of the first vaccination.
recipients of lot 1934/C-J625 vaccine. Recipients of
lots #979/C-IC564 and #81990D/18066/C-L215 are bled at
1, 2, 3, 6, 8, 12, and 24 months. The samples are
assayed for HBsAg, anti-HBc, ant1-HBs, and ALT.
Samples with ant1-HBs titers~ 25 mIU/ml may be tested
for the proportions of anti-! and anti-~ activity.
Samples may also be assayed for yeast antibody.
RESULTS: HEALTH CARE PERSONNEL/OTHER HEALTHY ADULTS

~-~-
(b) (4) Vacc1ne):
10 mcg Lot #979/C-K564 at 0, 1, and 6 months -

10 mcg Lot #819900/18066/C-L215 at 0, l, and 6 months
23841/2
l /3/86
00220
Study 795
RESULTS: (Contd) 1. Number Vaccinated:
Vaccine Injection No.

Lot _,_ -L -L
Lot C-lt.:564 148 146 126
Lot C-L215 97 97 94
2. Serolog1c Results:
Serologic data are available for 76 participants,
who received vaccine from lot C-K564, at 7/8
months. At that time, 100% (76/76) of the
subjects seroconverted {S/N ~2.1) and developed
protective levels of ant1-H8s (mIU/ml ~10). The
G~T at 7/8 months for all vaccinees and for
responders (either cutoff) it was 2143.1 mlU/ml.
Seven/eight month serologic data are available for
80 participants who received vaccine from lot
C-L215. Ninety-nine percent (79/80) of the
protective levels of anti-HBs (mIU/ml ~10) at that
time. The GMT was 2436.1 mlU/ml and 265S.2 ~IU/ml
for all vaccinees, while it was 2655.2 mIU/ml for
responders (either cutoff).
Refer to Table 1 for anti-HBs responses and ~Ts
Clinical follow-up data are available for 126, 94
and 74 participants, who received lot C-t564
vaccine, after injection number 1, 2, and 3,
respectively. Follow-up data are available for
96, 83 and 57 subjects, who received lot C-L215
vaccine, after injection number l, 2, and 3,
respectively. The overall frequencies of
complaints follow.
23841/3
l /3/86
00221
Study 795
RESULTS (corn.) :
Type of Vaccine Freouencv in£ bv Iniection No.
Co!!!!laint Lot l 2 3
Injection C-IC564 30(38/126) 29( 27/94) 22(16/74)

Site C-L215 16(15/96) 5( 4/83} 19(11/57)
Systemic C-K564 18(22/126} 17(16/94) 12(9/74)

C-L215 15(14/96) 8(7 /83) 9( 5/57)
Refer to Tables 2 and 3 for listings of specific

complaints after each injection. Maximu11
temperature data are presented in Tables 4 allld 5.
There were serious or alarming reactions

HBV Markers (Anti-HBC)
One subject who was positive for ant1-H8c prior to

vaccination, continued to be transiently positive for
anti-HBc post-vaccination. The subject was negative
for HBsAg and d 1d not seroconvert for ant 1-HBs as of
five months after enrollment in the study.
ALT Elevations
Two subjects with normal pre-vaccination ALT levels,

developed elevated ALT levels (1.5-2.0 times the upper
limit of normal) one month after the first inject ton
and one month after the third injection, respectively.
Another participant with an unknown pre-vaccination ALT
level, developed an elevated ALT level (2.0 times the
upper limit of normal) one month after the second
injection. All three subjects received vaccine lot
C-L215. They were negative for anti-HBc and HBsAg and
were not clinically ill.
One subject with an elevated pre-vaccination ALT level

(1.5 x the upper limit of normal) continued to have a
similar elevation one month after the first injection
of vaccine (Lot C-L215). He was negative for anti-HBc
and HBsAg and was not ill.
23841/4
1 /3/86
Table l
Antibody Responses Among Health Care · Personnel Following Vaccination with
10 11eg Injections of Yeast RecOlllb1nant Hepat1t1s B vaccine
Lots fl79 /C-K564 and l8199O0/18O66/C-l215 a-i 0, 1, and 6 Months 1n Study 119S
10 111Cg (Jot 197!l~-g564l 10 111tg (lot f81990D£18066[C-L215l

i with Anti -HBs GMT (1111U[111l} I with Anti-HBs lzt.1T (rmlU£111l l
Res~onderi @es~onden
T1nre ll'ilU/lal All mlU/1!1 mIU/1111 All mlU/1111
(1"1os.) S/M~2.1 ~ 10 Vacdnees S/N~2.1 ~ 10 S/N~2. 1 ~ 10 Vaccinees S/N~2.1 ~ 10
28 22 1.1 33.2 47 .4 23 20 0.8 26.1 31.1

(36/129) (29/129) (22/96) (19/9&)
2 83 r,r, 20.3 41. 1 66.9 71 58 8.3 32.S 44.8
(99/ 119) (79/11!1) (66/93) ( 54/69)
3 91 85 40.2 60.6 69.2 90 78 31.8 46.0 I

62 .1
(79/81) (74/87) (62/69) (54/69)
i gs 92 11.2 87.6 93.3 94 88 41.6 62.& 73.9

(112/118) (109/118) (83/88) ( 77/88)
l/8 100 100 2143. 1 21 43.1 2143.1 99 gg 2436. l 2655.2 2&55.2

(76/76) (76/7fJ) (79/80) (79/80)
0
0
rv
rv
"'
23841-6
1 /':1/Af..
Table 2
PATIENT COUNT CLI NICAL CONPlAINTS
RECOl1ftlllAHT MEPA111H 8 VACCINE
STUDY 0795
TIUATffENT
LOT tl\ll18ER [1(561t
DOSE 10 MCG
PATIEHT CLASS H£ ALTtt CARE PERSONMEL
I TOTAL YACCINEES C 148 PATI(NTSI • D05E 1 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATiml I tUIIIER
CLIN[CAL
COttPLAlNTS
1----------------------------------------------------·-----------------------I
I I I l I t • J I It I 5 I
NITH
ICottPLAIHT9
u•••••••••••••••••••••••••••••••••• •••••••••••l•••••••••••••••••••••l•••••••••• l•••••••••• l••••••••••l•••••••e•I••••••••••
I
REACTIOH, LOCAL I INJECT . SITE J J l6 I• 11
•
I 6 I• 2 II O II O
•
I I• ]8
I C tl'l.6Y.) I C 8.17.) I C " -8Y.) I ( l.6Y.) I ( t .OY.I I I O.OiO I I I 30.27.1
-----------------------------------1----------
I
---------- ---------- ---------- ----------1----------
o I •
---------- -----------
PAIN 2S a
I H.e:o
"
I
1
6.JY.I I J.21.1 C 0.8)0
27
I O.OY.I I ,(
I
•. ,in I 21.'li(I
SOIIENl:SS • 7 t O O O I t 7
S.6Y.I I l.6Y.I C O.OY. I C o.o;o I 0.07.1 I I 0 .01.1 I 5.6Y.I
TEHIIERNESS • 2 O O O O •I O 2
l.6)0 I , .01.1 C O.Ol!) I O.OY.I I o.o;o • I 0 . 01.1 I 1,6?.I
I
SMELLING • 1 l 1 0 0 • 8 1
o.eY.I C G.8l0 I 1 . 8)0 I 11.0lO I 0.1?.I I I o . ox, I 0 .81. )
I
l'IM!llIS llTCHlNII I I O t 1 l I I O 1
I , .01.1 I O.OY.I I • • ,1., I 0.8,0 C 0.17.1 I I o.ex, I o.e:o
I
IECCIIYttOSts I l 1 0 0 11 • G l
I t.81.1 I 1.87.1 I , .ox, I o.o:o C 0.01.1 • I e.o:o I 0.81.9
omn 1 :, 1 o D • I• o J
I c 2.ttio , o.e:o I I o.o;o I I o.D7.t 1 0.01.t I , 0.01., I c t.4i!t
------------------·---------------- Il----------l----------l----------
sYsr£HJt 11 I 9 I 7
l----------l------.
I S I t
. ---l----------1----------l-----·-···-
I It I I f:I!
I I 8.7)0 I I 1.uo I I !f.67.) I I lt.17.) I I 1 .67.J • I J.t:o I I I 17.51.1
-------------------------------------------------·---------------------------------------------------·----------·-----------
I I I I I I I
I II I I 7 I s I z I• I I 19 ~
&MOLE l!OIIY/Gtt!ERAL
I
I
I ,.])0 I I
I
'
7.11.J I
I
I !J,67.1 • (
I
4 .97.I I I 1 .,1.1 I I
I
J.2;0 I
I
I I 15.11.1
I
Cfflll9 I 0 I l I 0 I 0 •· • I • I I l
• C ,.01.1 I I D.87.J I I e. o;,. 1 I c •• ,1., •I I o. e r.1 • I e.07.1 I I e 0 . 8?.I 0
SWEATING
I
I , I• I
I
I 1 •• 1
I
I l •I 1
I
I
I
I l
0
"'
N
I I • .07.1 I l • .87. 1 I 1 o.87.) I I t . ar., I I o.a1.1 I I e .a:o I I I 0.111.) ~
Table 2 (c:ont)
PAlJEHl tOUHl CLINICAL CIJffllLAIHT9
RECotllIHAHT HEPATITIS 8 VACCINE
STUDT 07'95
tllf:AT11£NT
LOT tM18ER CK5•4
DOSE 10 ncs
PATJ[lfT CLASS HEALTH CARE PERSOHNEl
-------------------------·---------------------------------------------------
I .-------------------· --------------·-----------
TOTAL VACCJHEfS I 1•8 PATIENTSI - DOSE l I
1---- ----------------- - -- -- --------- - ----------------------------------------I
I OATS POST VACCINATIOt4 I HUl1BER
CUNJCAL
CDffl'lA JtfT9 I 0 I 1 I 2 I ] I I s .
1----------------------------------------------------------------------------I
I
NllH
ICOtlPLAIHTS
aue~•eaea•a~•~••••••••••a•••••~•••• •••••••~•• •••••••••• •••••••••• •••••••••• •••••••••• ••••••a•a• ue••a••aaa a•a•••••••
FATtGUf/NEAl<NE!l!!I
I •
1.2;0 I •
l,2)0 I
l
t.toY.I I
t
1.6)0 I
0
0.0)0 I
l
o.a,:t (
10
7.97.1
HEADACHE ] 4 l l l ] 10
( t.ltlO ( l.l!XI I t.4Y.I ( 0.8Y.I I o.ax, I t.4)(1 I 7.91.)
CHEST PAIN 0 0 l l 0 0 11
( o.o:o I 11.01.I ( l . 8Y.) ( 0.8%1 I o.o:o ( ,.o,:, ( 0,8)0
ILLNESS, tc09 t 1 0 0 0 0 t
( 1.61.) I D.81.) ( D.D1.I I D.07.1 I 0.0,:1 I o.o:o ( 1.61.1
IIE!IPIIIATDRY
( •
o.,:o (
0
I.DY.) I
1
0.8)0 I
1
D.87.1 (
l
0.8:!I I
l
o.az, (
l
0.81.1
RHINITIS
•
0.1)0 I
0
I.OZ) I
1
o.ex, (
l
0.87.1 I
1
0.8'(1 I
l
o.ax1 I
1
1.81.)
PHARYNGITIS t SOR! THROAT I I I 0 1 l l 1 l

I t 0.DXI I o.ox, I 0.8:!) t 0.8Y.I I l.8Y.I ( ,.ax, I 0.8Y.I
I
ffllSCULOSl<l:U:TAL' I
II
1
o.er.1 f
•
I.Or.I t
0
0.0)()
•
0
1.0)(1 I
0
O.DlO (
8
8.0lO (
I
, . ax,
I
"YALCIA I l 0 0 0 0 e 1
II 0.8?.I O.Ol!I I 0.0)0 I o.o-,o I o.or., I o.ox, I e . ax,
I '
OJGlSTIVE 9YSTE1t I
I
2
1.6lO I
0
o.o:o I •
1.0,0 I
0
0.0?.t I •
o.o:,o I
1
0.8)(1 I
l
t.4Y.I
NAU,EA I !IOI OI OI OI 11 IS
I r 1.61.1 I c 0.0:1.1 I • e.ox, I c o.o;o I I o.oin I 1 ,.ax, I I , t.1t1.1
-----------------------------------1----------l-------
PIRsmts Nl'ffl tOtfl'LAtNTS I 40 I 18
·--1----------I----------I----------I----------I----------I-----------
I lt I 6 I 2 I 4 I I "'
0
0
I I ll.71.1 I I lft.llO I I I I I I I I I f I
9.5lO ft.81.t l.t.Xl
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
J.UI '!18,9l0
"'
rv
C
PEl(SOUS &11111 NO C:ottl'UINTS I 86 I ua I 11 ♦ I 12D I 124 I 121 I I 77
I I 68 . JXI I C 85.7XI I I 90.5?.I I I 95.21.1 I I 98.ltY.I I I 96.lll!I I I I 61.IXI
Table 2 (cont)
PATltNT COUNT CLINICAL Cot1PLAINTS
RECOlfBINANT HEPATITIS B VAtCltlt
ST\JDY 1 07-JS
TREAT'1lNT
l Ol NUIBUf CK5•'1
DOS( I 19 tlt8
PAlUNT CUSS: HEALTN CME PER!ONll£L
• TOTAL VAtCltlH.S C 1'18 PATUHTSt - DOS£ l I

•----------------------------------------------------------------------------1
• DAYS POST VACCINATION .
• IM111£1t
CLINICAL •----------------------------------------------------------------------------• MI TH
tOl1PlAJH1S • II I 1 I 2 I J • °' 5 • I ICOffl'lAINTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• l•••••••••a•••••••••••••••••••••• I••••••••••
-----------------------------------1----------•----------•----------•----------l----------•----------
,cRSONs MITH HO DATA • 21 • 21 • U • 21 • 21 I U
l----------l-----------
• I U
I I 14.JY.J I I l'I .V.l I I 1•.1;0 I I 1•.JY.I I I 1,.JY.I • I 14.fflO • I I 14.J;o
0
0
IV
rv
Ill
Table 2 (cont)
PATIENT COUNT CLINICAL COttPLAINT9
RECONBINANT HEPATITIS B VACCIN£
STUUl 0795
1REAT'1tNT
lOl IIUtlBUl Ck564
DOSE U HCG
PATIENT CLASS HEALTH CARE PERSONH£l
I TOTAL VACCltlEU f 1"6 PUIEHTS I - DOSE &! I

1----------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I HUHBEII
tllHICAL
totll'LAIHTS
l----------------------------------------------------------------------------1
I O I 1 I t I J I " I 9 I WITH
ICOt1PU!NT9
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
I I I I I I I I
REACTICJ. LOCAL IINJECT. SITU I 20 • 17 I 7 I J I 1 I O I I 27
I C tl.]lO I C 18.UO I C 7.47.) I C J.tY.I I C 1.1%) I I 0.07.I I I f H.77.1
-----------------------------------1----------
PAIN I U
----------•----------1----------1----------1----------
8 I J I I I O I O
---------- -----------
16
C U.8l0 C 8.97.1 I f J.tY.I f 0.0%1 I C O.OiO I C O.DlO C 17.0:O
I I I
SORENESS I 2 2 I O O O I 11 3
1.1%) I t.1:O f t,07.) f 0.1%) C O,OiO I I I.DY.I f J.27.J
I
TENDERNESS I 1 I 1 1 I I O Z
1.lZ) I 1.lU C 1.llO l 1.1%1 I O.OlO I' I 0,DlO I 2.1%1
I'
ERTTHElfA CREOUESS I I l l 1 0 O I D 1
1.17.1 I 1.1%) C l.ll!I C o.o;o f o.o:o I I o.o:o f 1.\;0
I
STIFFNESS/TIGHTHHS • l O O I O t O 1
1.llO C 0.0)0 C o.o;o C O.GlO f 0.07.) I C 0.07.) f 1.11.1
I I
PRlRlflS ClTOtJHGI I l 2 1 0 0 t I 2
1.lY.I f Z.17.1 f 1.1:0 C 0.0%1 C O.0Y.I I, C 0.07.1 I 2.1:0
I
NVHBUESS I l O O O O I O 1
1.lY.J C I.DY.I C 0.11.I f 0.07.1 C 0.0,0 I f l.ll'-J C 1.11.1
I
Uffl'HADENOPATNT, REGIONAL I O I l l l O I 9 &!
,.ox, I I t.UO f 2.uo C 1.17.1 C o;oio I C •• ,:o I 2.17.1
I I
ECCHYHOSJS I 1 I I O 1 l I 8 2
l.IlO I f 1.17.1 I D.o:o C 1.11.1 ( 1.i;o I C t.OXI f 2.1:0
I I
PARESTHESIA I 1 I 1 I I O I O I
I C 1.17.1 I ( 1.1:0 C ••• Y.I I •••Y.) I ( O.Ol(J I I ,.DY.I I I f 1.17.)
-----------------------------------1----------1----------l----------l----------l----------l---------·1----------•-----------
srsnnic I , I e I " I 2 t 2 I o I • 16
0
0
I t '1.67.) I C e.s:o I C ... J)O I I Z.lY.I I C l.llO I I o.o;o I I C 17.DlO "'
N
0-
Table 2 (cont)
PAT IENT COUNT CLINICAL CottPLAINTS
IIECot18INANT HEPATITIS II VACCIHE
ST\JllT 07'5
TREATHEHT
LOT IMRIER I CK56"
DOSI! 10 t1CG
PATIENT CUSS: HEALTH CARE PERSOMffaL
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCltlEU I 1"6 PATU:HTSI - DOSE ! I
1----------------------------------------------------------------------------I
I
CLINICAL
OATS POST VACCINATION I IIUHSER
COl1PLAINl!I
1----------------------------------------------------------------------------I
I 0 I 1 I z I J I
WITH
I COl1PLAJHTS
I I
" 5
waP•••••••••••••••••••••••••••••••• ••••••••••••••••••••••••••••••I•••••••••• ••••••••••l••••••••••l••••••••••l•••a••••••
I
!ilHOLE BODY/GENERAL 8
8.SlO I
s
5,l:'.t
J I
I c
1 1
• n
FATIGUE/WEAIIHESS
' s
I 1.21.1
I
I
1.lY.l I l.Ut I 0. 01.I I ll.81.l
I "
4.llO I 5.l:'.t
J
1.1:'.)
0
1.0)()
0 I 6
' I .DX>
( ( I 0.01.I ( 6,,.lO
HUOACHE ,. l z 1 I
• II
( 4,llO I 1.1:0 ( Z.lXI ( 1.llO
• l.IXI ( o.o:o I a.sx,
JLLNESS, NOS 0 0 0 0 1 0 l
I O.OiO I D.07.I I o.ox, I 1.07.1 I l. l XI 1 .01.1 l.IXI
' '
INFECTIOUS STMJRONl:S
I
0
0. 07.t I
0
O.Ol'.t
0
0.0)0 I
1
l.17.)
1
l,ll'.I • l
C C
' 0.01.1 I 1. 1x1
!IF LllfNZA, HOS I 0
1.0:r.1 I
0
o.ou I
0
0.111.) I
1
l.17.) I
J
l.ll'.1
'
0
1.11.1 ''
I
I
I
J
l. ll'. l
RESPIRATORY l 0 II 0 0 0 I 1
I 1.17.) I 0.0)'.) I 0.111.1 I 0,0)() I t .07.1 I 11. 01.1 I I l.llO
UPP£R RESPIRATOR't INFECT., NOS 1 0 II 0 0 0 1
I 1.17.1 I o.o:o I 0.111.) I 11.0;0 t.07.1 I , .01.1
MIEntc AtlO l YttPHATJC 0 1 0 0

' 0 0
I l.llO
1
I o.o:io I 1.0:r.1 e .o:u ,. 11:r.1 t .01.t
l.llO
' ' I
( I l.liO
lYttPHAOIEHOPATHY, CERVICAL
I
0
t. 07.t I
1
l.ll!I (
0
1,0;0 I
0
O,OY. I I
• I l
11.tll!I
0
0.01.1 I
1
1.1:r.1
I
OIGE5TtVE 5YSTEtt l
1.1;0 (
t
Z.ll'.1 (
1
l. l XI (
0
I. DY.I I • I
O.O:O I I
II
8.01.t I
]
J.ZXI
I 0
UYSPEPStAIKEARlBUIIM I 0 1 0 0 II I 0 1 0
0.07.1 I 1.ll'.J I O.OXI C o.o:o ( o.o:o I 1 0.01.1 I l.liO N
I
NAUSEA I 1 t 0 0 0 I 0 J ....
1\,1
1.17.1 I Z,1'0 C t.01.1 I 0.0:'.I C o.ox1 I 1 0 .07.1 I ].tlO

Table 2 (cont)
PATIENT COUNT CLINICAL CottPLAINTS
RECOtlBIHANT HEPATITIS B VACCINE
STUIY 0795
TREATtlENT
LOf tUISER CK564
DOSI! 10 t1CG
PATIENT CUSS HEALTH CARE PERSot4NEL
I TOTAL VACCIHEU ( 146 PATUNTSI - DOSE t I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I tu1BER
CLINICAL
COttPlAINTS l----------------------------------------------------------------------------1
I O I 1 I 2 I 3 I 4 I 5 I MITH
leottPUIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
Vtlt1tTIIIG I O I O I 1 I 0 I t I D I I I
I I o.ox, I I 0.01., I I 1.11., I( 0.0%1 I( 0.01., I I 0.01.1 I I( 1.11.1
I I I I I I I I
NERVOUS SY9TEtt I 2 I o I D I o I o I o I I 2
I ( 2.UO I I 0.01.J I I 0.01.I I I o.ox, I ( t.01.)I ·I 0.01.1 I I I t.11.1
I I I I I I I I
VERTIGO/DIZZINESS I 2 I 0 I a I D I o I O I I 2
I I 2.11.1 I I 0.01.1 I I 0.0XI I I 0.OXI I ( 0.0XI I I 0.01.1 I I I 2.lXI
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS MITH Cot1PLUMT9 I 28 I 21 I 9 I 5 I 3 I O I I n
I I 29.8i0 I I 22.JY.I I I 9.61.J I , 5.31.1 I 1 1.21.1 I I o.o:o I I 1 35.11.t
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l
PERSDtlS NITH NO COtlPLAINTS I 66 I 73 I 85 I 89 I 91 I 9ft f I---_,_------
61
I I 10.2;0 I I 77,7Y.J I I 90.4i0 I I 9".71.1 I I 96.81.1 I 1100.0:0 I I I 64.9:o
-----------------------------------1----------l----------l----------l----------l----------l----------l----------1-----------
PERSOHS MITH NO DATA I 35 I 35 I 35 I 35 I 35 I 35 I I J5
I C 27.11.l I C 27.lXl I I 27.lXt I C 27.11.1 I C 27.lXI I C 27.lXI I I ( 27.11.J
0
0
1\1
I\)
CD
Table 2 (cont)
PATIEHT COUHT CLINICAL COl1PlAlNTS
RECOt18IHAtlT HEPATITIS 8 VACCIIIE
5TUO'f 0795
TREATtlEKT
LOT IIVIIDER CK56lt
DOSE 10 HCG
PATIEIIT CLASS HEALTH CARf PERSONNEL
I TOTAL YACCltlEES I 126 PATIENTS I - DOSE J I

l----------------------------------------------------------------------------1
I 0.l'fS POST V.lCCltlATIOII I tu'BEA
CLitlJCAL
C011PLAINTS
1---------------------------------·
I O I l I 2 I
-------------------------------------------1
l I Ii I S I
MITH
ICOIIPLAJNTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION, LOCAL I INJECT. SITE I I 15 I 9 I 3 I l I O I O I I 16
I C 20,17.1 I C 12.2Y.I I I li.11.1 I C l.1t1.I I c 0.01-1 I c 0.07.I I I c 21.67.1
-----------------------------------
PUN
----------1----------
12 I 5
----------
O
----------
o ----------1----------
O I o ---------- -----------
It
C 16.27.1 I C 6.87.J I 0,01.1 C 0.01.1 C O.OiO I I 0.07.J I 16.27.1
I I
SORENESS 2 I 0 O O . o I O 2
C 2. 7)0 I C O. 01. I I O. o;o C O. 07. I I O. 07. I I C O. 07. I I 2. 71. I
I I
SWElllllG l I l l l O I O 1
C 1.liY.J I C 1.liY.I I 1.li7.J C l.4Y.I I O.o:o I C 0.07.J C l.li7.I
I I
Pl!URITIS I ITCHINGJ O I 4 2 O O I D Ii
I O.OY.J I I S.4Y.I I 2. 71.J C 0.01.1 C D.CliO I I 0.07.1 I S.li7.I
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
I , I " I s I I I r I
snTEHIC
I c a .11. 2 J
1 I c s. 4Y., I 1 , • a:o I c 2 • 11., I , ,. .1Y. 1 I 1 2 • 77. , I II c 12. 2x
•
1
----------------------------------------------------------------------------------------------------------------------------
WHOU IIOOY/GENERAL I J
"· 17., C
1
1.47.J I
l
l.t1iO
'
I
I I
l
l.'tlO (
1
l.4Y.J I
0
0.07.) C S.liY.I
Ii
I
FEVER ITEHP. HOT REPORT!DJ I 0 l l I 0
o. 01.1
0 0 1
0.07.J C 1.41-1 1.1tr.J I I C O.OiO C 0.07.I ( l.4i0
SENSATION OF WAlfflTH, GENERAL I 1 0

' 0
I
I 0 0 0 l
1.li?-1 ( 0.07.1 C 0.0?-1 I ( G.01-1 ( 0.07.1 C 0.07.1 C 1.lii!l
I
FATIGUE/IIEAKNESS I 2 l 1 I 1 1 0 J
2.7)0 1.4)0 I 1.ttY.l ·I C l.li7.I 1.47.1 C 0.07.J li.liO
'
( (
I
HUOACHE I 1 0 0 I 1 0 0 2
1.<tY.I I O.Cl?. I I o.ox, I c 1.4:'.I C 0.01.I C 0.07.) I 2.77.1
I 0
0
INFECTIOUS SYHIAOM£9 I 0 0 D I
I t
0 1
1.4?.I
D
I
l
l.47.1
I\)
rv
0.0:'.I I 0. 07.1 ( o.ox1 0.07.1 ( G.O?.I
' ,0
Table 2(cont)
PATIENT COUNT CLIHICAl COl1PLAIHTS
RECOltBIHANT HEPATITIS 8 VACCIIIE
STUDY I 0795
TREATHENT
LOT HUlfflER CK564
DOSE 1 10 11CG
PATIENT CUSS: IIULTH CARE P£R!IONfEL
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES I 126 PATIENTSI - DOSE J I
1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I HUHBER
CLINICAL 1----------------------------------------------------------------------------I WITH
Cot1PUINT9 I 0 I 1 I 2 I J I 4 I 5 I ICOMPUIHTS
.................................................................. ·······-·· ........•...............................
I
INF LUWZA, NOS I 0 0 0 0 l 0 l
0.0)0 0.0)0 0.0)0 o.o:o 1.41.1 0.01.,
11USCULOSKELETAL
II '
I 2
' 2
' 2
I
0
I
l
' l
' l.4l'.I
:,
2 . no I 2.7)0 2. 77.1 I o.o:o I 1.41.1 4.UO
AATHAALGll IOTIIERI I 1 1
' 1 0 0
' l.4i0
0
(
1
1.4i0 ( 1.41.1 ( l.4i0 I o.o;o I 0.01.I 0.0:1.1 l.4)0
SHOULDER PAIN I l 1 1 0 0
' 0
' 1
1.4i0 I 1.4:0 I 1.47. I
I
I o.o:o
I • o.o;o
• a.o;o
• 1.41.1
OTHER I 0 0 0 0 1 l 1
o.o:o • o.o;o ( 0.07.1 I o.o;o
' l.lti'.I I 1.lii! I
I
I 1.4:'.I
DIGESTIVE SYSTEl1 I l 1 2 l 2 l J
l.lil'.I C l.4i0
' 2. 71.1 I l .lt1. I
• 2.710
• 1.41.) ( ♦ .17.1
DYSPEP9IA/HEAATIIUfH I 0 0 l l l l 1
O.OlO
• 0 . 07.) C l.4i0 I l . 4XI
' l.47.)
'
1.4)!)
• l.lt7.I
DIARRHEA I 0 0 l 0 l 0 2
I I
I
0.01.1
' O.OlO I 1.47.1 I o.o:o
• 1.41.1 I O.Ol'.I I Z.7l0
NAUSEA I l 1 0 1 l 0 2
I •
I
1.47.J I 1.ftlC J
• 0.07.1 t l.ftlO
• 1.lti!) I 1.07.1 I 2. 77.1
UAOGEHITAl SYST£H I l 0 0 0 0 0 1
I I 1.41.) I 0.07.) I 0.01.1 0.07.1 1.07.1 O.OiO 1.ltl'.1
I ' ' ' '
UAIHARY TRACT lHfECTIOH I l
l.lt7.J I
0
0.07.1 I
0
0.07.1 I
0
0.01.) I •
0.07. I
0
0.07.1
1
1.47.1
' '
PSfCHlA~IC/8EffAVIOffAL I 0
0.07.J I
0
•
0.07.)
l
•
0 .07. I
0
0.07.1
l
1.47.1
0
0
INS011HlA/OISTIJRBED SLEEP I 0
0.07.J
0
I
0
( 1.47.1
l
I
0 I
' 0
I
1
rv
ul
0
0.07.) t 0.07.I
' O.Oi!J
• 1.47.1
• O.Oi!I I I o.o;o I l .41.J
Table 2 (cont)
PATIENT COl.tfT CLINICAL COl1PLAINTS
RECotlBINAHT HEPATITIS B VACCINE
STUDY 0795
TR[ATl1ENT
LOT HUIIBER CK56't
OOSE 1 10 t1CG
PATIEIU CLASS: HEALTII CARE P£RSOtH:l
I TOTAL YACCINUS I 126 PATIENTSI - DOSE J I

1----------------------------------------------------------------------------I
I DAYS POST VACCIHATIOM
·
I NUN8ER
CLINICAL
CotlPUINT!I
1----------------------------------------------------------------------------•
I O I 1 I I! • 3 I 4 I 5 I WITH
ICOMPLAINTS
•••••••••••••••••••••••••••••••••••1••••••••••1••••••••••1•••••••••••••••••••••1••••••••••1•••••••••••••••••••••1••••••••••
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOtlS MITH COOPLAINTS • 19 I lJ I 8 I 3 I 3 I Z I I 22
I, u.n:1 I, 11 . ,x1 • , 10.ex1 I 1 't.1:O I, 4 . 1x1 I, t.7%1 I I I n.n1
-----------------------------------•----------1----------1----------1----------I----------I----------I----------I-----------
PERSOMS MtTH NO COt1PLAIMTS I 55 I "1 I 66 I 71 I 70 I 71 I I St
I I 74.JY.I • I 82.ftY.1 I I 89.2XI I I 95.97.I I I 95.9XI I I 97.JXI I I I 70.J%1
-----------------------------------1----------1----------1----------t----------1----------I----------I----------I-----------
PERSONS MITH NO DATA I 19 I 19 I 19 I 19 I 2D I 20 I I 19
I I 20.47.1 I I 20.4XI I I 20 . 4XI • I 20.47.1 I I 21.SXI I I 21.SXI I • I 20.4%1
0
~
N
""'
Table 3
PATIENT C~T CLINICAL CottPLAINT!I
RECONBINANT HEPATITIS B VACCIHE
STUDY 0795
TREATMENT
LOT IIUtlllER cun
DOSE I 10 t1CG
PATIENT CUSS: HEALTH CARE PERS(]NtlfL
I TOTAL VACCiltEES t 97 PATIENTS I - DOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST VlCCIHATIOH I tlJt18ER
CLINICAL 1----------------------------------------------------------------------------I WITH
COHPUINTS I O I l • 2 • l I 'I I 5 I IC011PUIHTS
••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I • I I I I •
REACTION, LOCAL I INJECT. !IITE I I 12 • 4 • 4 I 2 I t I t I I 15
I 1 12.s1.1 I , 4.2i1 I 1 4.2i1 I 1 2.1x1 I , 2.1Y.1 I I r.11.1 I I , 15.6Y.I
-----------------------------------1----------1----------1----------I----------I----------I----------I----------I-----------
PlIN I 8 I 1 I l I O I O I O I I II
a. 1i I I 1 1. ox I I 1 1. o;o I , o. 01. 1 I 1 • . oY.1 I I o. 01. 1 I I I e. JY. I
I I I I I I I
SORENESS I 2 I l I l I II I o I o I I l
2. uo I ( 1. o:o I I 1. 01. I I ( 0. OY. I I I I. OY. I I I II. 07. I I I ( l. lY. I
I I I I I I I
ERTTHEnA I REDNESS! I O I 1 I l I O I o I o I I 2
0.01.I I I l.OY.I I I l.OY.I I ( O.OY.I I I O.OY.I I l O.OY.I I I I t.lY.I
SWELLING I 1 I 1 I 0 I 0 I 0 I 0 I I 2
1.01.1 I c 1.01.1 I 4 0.01.1 I t 0.01.1 I t 0.01.1 I , 0.01.1 I I I 2.1:0
I I I I I I I
PAPULEl!II I 0 I 0 I 1 I 0 I 0 I 0 I I 1
( O.OY.J I t o.o;o I t 1.0;0 I I O.OY.I I I D.01. I I I o.o:o I l.OiO
PRUllTIS IITCHIHGl
LYHPHADENOPATHY, REGIONAL
I
I
0
O,OY.I
1
I
I
I (
I
0
O,OY.l
l
I
I
I (
I
l
l , Oi!I
l
I
I
I
I
I
l
1.01.1
l
I
I
I I
I
1
1.01.1
1
I
I
I c
•
1
1.0;0
1
I
I
I
I
.
II '
I
•
(
1
1.0:0
2
I I l,OY.I I l l.OY.I I I l.OY.I I I l,OY.I I I l.OY.I I t l.OY.I I I l 2,17.1
-----------------------------------1----------l----------l----------l----------•----------l----------l----------l-----------
srsnHIC I 5 I 10 I 5 • t I l I O I I 14
I I 5.2i!I I I lD.4:'.I I I 5.21.1 I I Z.IY.I I I l.OY.I I I 0.01.I I I 4 l't,6Y.I
----------------------------------------------------------------------------------------------------------------------------
I I I
WHOLE BOOY/GEHERAL I 5 I s I J I 2 I 0 I 0 I I 10
s.2i1 I t 5.27.1 I I J.lXI I I 2.1:'.I I I 0.07.I I( O.D1.1 I I I 10.41.1
I I I I I I I
CHILLS I 0
O.OY.I
I
I I
1
1.0Y.I
I
I I
0
0,01.I
I
I I
0 I
o.o;o I ,
0
0.117.1
I
II • II
o.o;o
I
I I
l
l.OY.I 0
I I I I I I I 0
SWEATING I 0
o. DY. I
I
I I
0
0.01.1
I
I I
1
l.OY.I
I
I I
•
O.OY.I
I
I I
0 I
o.o;o I , • I
a.ox, I
I
I I
1
1.01.1
rv
~
N
Table 3 (cont)
PATIENT CotMT CLINICAL Cot1PLAINT5
RECot'SINANT HEPATITIS B VACCINE
STUOY 0795
TREATl1EITT
LOT MJIIBEA Cl215
OOS! 10 Ht&
PATIENT CLASS HEALTH CARE PER~EL
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES I 97 PATIENTS) - OOSE 1 I
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I tu18ER
CLIHICAL
Cot1PLAIHTS I 0 I 1 I t I ] I ,.
l----------------------------------------------------------------------------1
I 5 I
NITH
ICOttPUJNTS
•••••••••••••••••••••••••••••••••••!••••••••••
I
•••••••••• ••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
I
FA TIGUE/NEAKtlESS I 2 t 1 I 1 0 0 6
z.i:o I z.uo ( l.0iO I I l.OiO I o.o;o I 0.0iO I 6.31.J
HEADACHE I l z 0
I
I 1 0 0 ,.
].11.1 I 2.uo ( O.OY.J I I 1.o;n I 0.01.J ( 0.0Y.I ( ,._ 21.'
I
LIGHTHEADED I 1 0 0 I 0 0 0 1
1.01.) I 0.01.1 ( 0.01.1 I I 0.0Y.I ( o.o:o ( O.0Y.t ( 1.01.1
I
ILLNESS, NOS I 1 :t 1 I 0 0 0
I c 1.01.I I Z.11.1 l.Oi!> o.o;,n 0.llO ( "
RESPIRATORY 0 1
' 1
' 1
I
l
O.0Y.t
0
I "· 21.1
1
( 0.0iO ( 1.0iO ( 1.01.1 ( 1.0Y.I ( l. 01.) ( 0.0:1.1 I 1.01.,
PHARYNGITIS I SORE THROAT I 0 1 1 I 0 0 1

( 0.01.1 ( l.OY.) ( 1.01.1 ( 1.0Y.I ( o. 07.) ( 0.0Y.I I 1.0XI
UPPER RESPIRATORY INFECT., NOS 0 0 0 0 1 0 1

( 0.0Y. I ( 0.01.1 I D.0Y.I I o.o;o 1.07.t I.OZ) ( 1.0:1.1
'
(
COUGH
(
0
0.0Y. I (
1
1.01.1 (
0
D.0Y.I (
1
l.0Y.J (
0
o.ox, ( •
0.0Y.t (
1
1.0;0
mscULOSKUETAL 0 0 1 0 0 D 1
( o.o;o ( I.OY. I ( LOY.I ( o. 07. t I o.ox, ( 0.01., ( 1. 07. J
Al!THRALGU, ttot_,AATICUUA 0 0 1 0 0 0 1
I 0.01.1 I I.0Y.I I l.01.1 I o.o;o I o.o;o I 0 .07. I ( I. D7. I
DIGESTIVE SYSTEn 0 J 1 1 0 0 ,.
0.OY.I ( J.llO I 1.0;0 I 1.0Y.I I 0.0Y.I I 0.0Y.l I ... 2;0
DYSPEPSIA/ff(ART8URN I 0
O.0Y.I I
1
1.0Y.l ( •
0.OY. I I
0
0.0Y.I I
0
o.o;o I
0
o.o;o I
l
1.0Y.I
0
0
rv
1.,,,1
OIAARNEA ~
I 0 0 0 I 0 0 l
0 .0Y.I I O.OY.I ( 0.0Y. I ( 1.0;0 I 0 . 07.J ( 0.0Y.t I 1.0:0
Table 3 (cont)
PATIENT C<XMT CLINICAL CottPLAINTS
RECOtl8INANT HEPATITIS B VACCINE
STOOY 0795
TREATMENT
LDT IIUtlBER ClU5
DOSE 10 11CG
PAtIENT CLASS HEAlTH CAIIE PERSotlllEl
I TOTAL VACCINEES C 97 PATIENTSI - DOSE I I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION . I .u18ER
CLINICAL
Cot1PUINTS
l----------------------------------------------------------------------------1
I O I 1 I 2 • 3 I '\ • 5 •
WITH
ltottPLAIITTS
•••••••••••••••••••••••••••••••••••1••••••••••1••••••••••1••••••••••••••••••••••••••••••••••••••••••••••••••••••1••••••••••
I I • I • • I •
tlAUSU I 0 • 2 • 1 • o • o • o I • 2
• ( 0.07.1 • ( 2.17.I I C 1.07.1 I C o.o::o I l o.o;o I l 0.07.) I I I 2.1:0
I • I I I I • I
PSYCHIATRIC/BEHAVIORAL I 0 I l I 0 I 0 I 0 I o I I 1
I I o.ox, • I l.07.t I l 0 . 07.1 I I 0.07.1 I C 0.07.t I C 0,07.1 I • C 1.07.1
I
DEPRESS!~ I o I• l
•
I O
•
• o •I o II o II •
I l
I C o.o::o I I 1.0;0 I I O.0XI I C D.07.J I I 0.07.1 • I 0.07.t I • I 1.0;0
-----------------------------------•----------l----------l----------1----------1----------1----------l----------•-----------
PERSatlS WITH C01PLAINTS I 15 I 13 I 9 I 4 I 3 I 2 I I 26
I, 1s.6XJ I c n.s;o I c 9.4XJ I, 4.2x1 I < 3 ,1;0 Ic 2.1x1 I •cu .1x1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSatls WITH NO tottPLAINTS I e1 • n I 111 I n I 93 I 'l<t I I 10
I C 114.'tXI I I 86.57.I I c 90.6Xt I C 95,0iO I I 96,9lO I I 97,9Xt I I I 72,97.J
-----------------------------------1----------l----------l----------1----------I----------I----------I----------I-----------
PERs01tS WITH NO DATA I l I l I l I l I 1 I l I I l
I C 1.07.t I C 1.07.I I l 1.0;0 I C 1.117.1 I l 1.07.t I I 1.07.t I I C 1,07.J
0
0
IV
u,I
~
Table 3 (cont)
PATIENT C~T CLINICAL COMPLAINTS
IIECOIIBINAHT HEPATITIS 8 VACCINE
STUDr 0795
TRUTllEHT
LOT tltff18ER Cl215
DOSE 10 IICG
PATIENT CUSS HEALTH CARE PERSO!ffl
I TOTAL VACClNEES I 97 PATIEMTSJ - DOSE 2 •

1----------------------------------------------------------------------------I
• DAYS POST VACCINATION • NUt18ER
CLINICAL
COIIPUINTS
•----------------------------------------------------------------------------1
• 0 • 1 I 2 • J I 4 • 5 I MITH
•cOMPUINTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••••••••••••••••••••••••I••••••••••
I I I • • I I
IIEACTION, LOCAL IINJECT. SITU • 3 I 1 • l I l I 1 I 0 I •• 4
I 1 3.67., I 1 1.27.1 I 1 1.ex, I 1 1.2x1 I 1 1.2x, I I o.ox, I I 1 ,.er.,
-----------------------------------•----------•----------1----------1----------•----------•----------I--------
PAIH f 2 I 1 • 1 I 1 f . 1 • 0 •
.-1-----------
I 3
I I 2.t•Y.I • I 1.27.t • I · 1.27.I I I 1.27.1 • I l.2iO I I 0.07.t • I I 3,6?.I
II •• • • II • II I•
PRUIITIS I ITCHING I D o I 1 I 1 1 I o 1
• I G.D7.I I I O.G7.I • I 1.27.t • I 1.27.1 I I 1,27.t I I o.ox, • • I 1.2?.I
OTHER II l I •
O
I
I O
I
I O I O I O
I
I • I
I •
1 ·
I c 1.zx, t I o.ox, I 1 0.07., I 1 0.07.t I 1 0.07.t I I o.ox1 I I 1 1.2:0
-----------------------------------t----------l----------l----------t----------l----------l----------l----------•-----------
srs1Etttc f J I 2 I 2 • 1 I 2 I 1 I I 7
I I 3.67.) I I t.ftlO I I 2.ftY.I I I l.2lO I I 2.47.1 I I 1.27.1 I I I 8 . 4Y.I
--------------------------------------------- .------------------------------------------------------------------------------
MiOLE BOOT/GENERAL I 2 I 2 1 0 0 1 5
2.1,7.1 I 1 2.47.) I 1.27.1 ( o.o:o I o.o:o I 1.27.1 I 6.07.)
SENSATION Of WARttTH, GENERAL l D 0 a 0 a 1

I 1.27.1 I o. 07.1 ( 0.07.1 I 0 .CIY.I I G.0iO I o.o:o I l.2il. I
FA TIGUE/WEAKtlE 59 l 1 1 a 0 a 2
I 1. 27.1 I l.2iO I 1. 27.1 I 0 .O?.I I 0.OiO I 0.07.) I 2.4il.l
HEADACHE a 0 0 a 0 1 1
I 0.07.1 I a.ox, ( 0.0)0 I 0.0XI I o.oio I 1.27.1 ( 1.2;0
LIGHTHEADED 0 1 a a 0 a 1
( o.o:o ( 1.2X) I o.o:o I 0.07.1 I o.o:o I ,.ax, I 1.ZXI
ILLNESS, NOS D 1 1 a a a 1
o.o;o I 1. 21.1 I 1.l!lO I 0.07.1 I 0.07.1 I I.OXI I 1.27.1
0
0
RESPIRATOll'I' I 0 0 0 1 2 1 3
1\1
0.07.1 ( o.o:o ( o.o:o I 1.27.1 I 2.47.1 I 1. 27.1 ( 'J.6?.I
..,,
u,I
Table 3 (cont)
PlTIEHT COUHT CLINICAL COHPLlINTS
RECOHBINAHJ HEPATITIS 8 VACCINE
STOOT 0795
TRUlttfNT
LOT 11Utl8ER CL:Zl5
DOSE 10 11CG
PATifHT CUSS HEALTH CARE PERSOHHEL
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES ( 97 PATIENTS, - DOSE Z I
l----------------------------------------------------------------------------1
I DOS POST VACCINlJIOH I t1Ut1BER
CLINICAL
C0l1PLAIHT9
1----------------------------------------------------------------------------I
I O I l I Z I 3 I It I 5 I
NITH
ICotlPLAINTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••I••••••••••
AtllmlGllIS I SORE lllROAT I I 0 0 0 O
•IZ II 1 3
o.o;o ( 0.0Y.I ( 0.0Y.I ( o.or., I I t.4i0 I ( 1.zr., ( 3.6;0
I I
UPPER RESPIRATORY INFECT. , NOS I 0 0 0 l I 0 I 0 l
0.0Y.I ( o.o;o ( 0.0Y.I C 1.ZY.I I ( o.o;o I C o.o;o ( l.:ZY.l
I I
COUGH IO o 0 ll ot 0 l
0.0Y.I I o.oz, I o.o:o I l.:ZlO I I o.o;o I I 0.IY.1 I 1.21.1
I
CARDIOVASCUllR I l O O O O • 0 1
1.UO I o.oz, ( D.0lO ( 0.DY.I I O.0lO I( 0.oz, ( 1.ZY.I
I
BRAOYCARDIA/8RlDYARRHYTffttU. I 1 0 0 0 o I O l
l.ZlO ( 0.0iO ( O.o:o ( 0.0Y.I C O.0lO I ( 0.0Y.I I l.2Y.I
I
lfJSCULOSKElETAl. I 1 0 0 0 O I O l
l.:ZY.I I 0.01., ( o.o;o ( 0.01.1 ( O.0Y.I I ( 0.0Y.I C l.:ZY.I
I
ARTHRALGU IOTHERI I 1 0 0 0 0 I O 1
I 1.21.1 I 0.0;:1 ( 0.01.1 ( o.0Y.I ( 0.0;:1 I ( o.o;o I 1.21.l
I
DIGESTIVE SYSTEl1 I l l 1 0 0 f O l
I l.:ZY.1 C 1.2:r.J I 1.UO I 0.0:1.1 I O.0Y.l I I 1.11., I 3.6Y.I
I
DIARRHEA I 1 0 l O G I O 2
l. 21.1 ( 0. o;o I 1. :ZY. I ( 0. or. I I 0. 0:1.1 I ( 0. IY. I I :Z. 4Y. I
I
HAU5EA I O l O O II I 9 l
I ( a.or., I I 1.:z;o C O.OY.I I 0.0iO I O.0iO I I a.ox, I l.2Y.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOIISWITH COIIPUINTS I 5 I 3 I J I Z I l I l I I 10
I 1 6.01.1 I c 3.6;.o I c 1.,1.1 I c 2.<+r.1 I , J.6iO I c 1.2Y.1 I I , iz.o;o
-----------------------------------l----------l----------1----------1----------1----------I----------I----------I----------- 0
PERSotlS MITH NO COtlPUINTS I 78 I 80 I 80 I 81 I 80 I 82 I I 7J 0
I , 94.oio I c 96.ttxi I r 96.,r.1 I 1 97.6iO I c 96.4Y.J I c 98.8?.I I I l ae.o;o rv
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
PERS0t1S MITH NO DATA I 2 I 2 I 2 I 2 I :z I , 2 I I 2 ""'
0-
I , 2.41.1 I c 2.1+1.1 I t 2.11:1.1 I l t.41.l I c 2.r.:o I c 2.<+Y.I I I I Z.4Y.I
Table J (cont)
REC0118INANT HEPATITIS B VACCINE
STUDY 0795
TREATtlEHT
LOT tlJltoER Cl:!15
DOSE 10 t1CG
rA TIEHT CLASS HEALTH CARE PERSONNEL
• TOTAL VACCIHEES I 94 PATIENTSI - DOSE J • ·

1----------------------------------------------------------------------------I
I DAYS POST VACCittATIOH I NU1BER
CLitUCAL
tot1PUINTS
1----------------------------·
I O I 1 I 2
------------------------------------------------1
I l I I I ICot1PUIHT9
4 5
WllH
••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I • • I I • I
REACTION. LOCAL !INJECT. SITl:I I 6 I II I II I 6 I 4 I l I I 11
• c 10.5,O I C 14.07.1 I c l't.OiO • I 10.57.1 I c 7.07.1 I c 5.3,O I • t 19.37.1
-----------------------------------,----------
PAIH I t ---------- ---------- ---------- ---------- ---------- ---------- -----------
• I ].57.1
5
I "
7.0,O (
3
11.11:1.1
l
( "
7.0:t. I
f,
I 5 . 3,0 I s.3;O I 10.5)(1
TEHO£RNESS
I
I l 2 l l 0 0 ,.
• C 5.liO ( 1.s:o I 1.87.1 I 1.87.1 C o.o:o C O. 07. I I 7.0lO
I
ER'l'THEHA IREDHESSI I l l l 0 0 0 2
1.87.) I 1.11;0 C 1 . 87.1 ( 0.0iO I 0 . 0)() ( 0.07.1 I J.57.1
WARHTH I l l l 0 0 I t
1.87.1 ( l.lliO C 1.87.1 C 0.07.1 C o.o;o ( 0. 17.1 ( J.57.1
SWELLIH6 I 1 l l 0 0 I 2
1.117. I I 1.11:0 I 1.87.1 I 0.07.1 C O.0iO C 0.1;0 I J.57.1
PRURITIS I ITCHIHIU I O I l I t I l I l I O I I 2
I I o.o;o • C 1.87.1 I I 3.57.1 I C 1.87.1 • C 1.87.J I ( 0.0iO I • I J.5iO
-----------------------------------1----------•----------l----------•----------•----------l----------l----------l-----------
srsmnc I J I t I l I 2 I 2 I 2 I I s
I I 5.37.I • I J.SiO I I l.87.1 I I 3.57.1 I I J , 5i:) I I 1.5;0 I I I 8.8iO
----------------------------------------------------------------------------------------------------------------------------
,-iotE SOOY/GENERAL 0 I l I o. I 0 I 0 0 I I l
• ( o.o:o I c 1.8iO • I o.or.1 I c O.OXI • ( o.or.1 ( 0.0:'.I I I I 1.87.I
I
• I I I
•
HEADACHE I 0 I 1
• 0 I D I D 0 I
• 1
I D.07.1 • I 1.11;0 I c o.o:o I I o.07.1 II 0. O?.I ( 11.0Y.I • I I l.87.)
I I I I I I
INFECTIOUS S'l'NDROtfES I l I 0 I 0 I l 1 l 2
1.11;0 I c 0.07.1 I c o . o:o I I 1.117. J •
I I 1.8?.) C 1.8:t.) • • •
• I 3.5iO
0
I I I I I I 0
INFLUENZA, NOS I l 0 I 0 I I I l l I I 2
•
1.11;0 I c O.Oi'!I • C 0.07.1 I C 1.111.J I c 1.8:f.) C 1.8:t.l I • I 1.s:o
N
VI
--4
Table 3 (cont)
RECotlBINANT NEPATITIS B VACCIIIE
!ITUOT I 07'15
TREATMENT
LOT NUIIBER Cl215
DOSE 10 t1CG
PATIENT CLASS: tlEALTll CARE PERSOHHEL
I TOTAL VACCINEES f 94 PlTIENTSI - DOSE J I

l----------------------------------------------------------------------------1
I DllS POST V&CCINATIOH I IUl3ER
CLINICAL 1----------------------------------------------------------------------------I
I o I 1 I 2 I 3 I ft I 5 I WITH
COIIPlllHTS
.......... ,......................................................................
ltot1PllINT9
···········-·······················
RESPIRATORY 2 I l 1 1 1 1 3
I 1.s::o I 1 1.a:o I 1.e:o I 1.e:o I 1.e::o I 1 .ex 1 I 5.JiO
I
RHINITIS 0 I 0 0 1 1 1 1
I o.o:o I c o.o::o f 0.0XJ f 1.a:o I l,l!i!I f l.8i0 I 1,l!i!I
I
LARYNGITIS 2 I 1 1 0 0 0 z
3,Si!J I f 1.8)(1 f 1.8:n I 0 . 0XJ I o.o:o I o.o:o I J.SY.I
I
DIGESTIVE SYSTEN l I l l 0 0 0 l
l.81.I I C 1.e::o I l.81.J C 0 .01.J C o.o:o ( 0.01.I ( 1.e:o
OTHER I 11 11 11 OI OI OI I l
1.81.1 I C l.~, I I 1.81.1 I f 0.01.I I C o.o;o I f 0.07.1 I I f 1.87.1
I I I I I I I
HtRVOUS SYSTEM I O I l I O I e I O f O I I 1
0.01.1 I I l.8i!) I I 0.0i!I I I 0.01.1 I I 0,01.J I f D.01.I I I f l.81.I
I I I I I I I
VERTIGO/OIUINE99 I O I 1 f O f O I O I O I I 1
I f 0.0)0 I I 1.e;o I I 0,0%1 I C o.o;o I I · O.OY.I f f D.0)0 I I f l.8Y.I
-----------------------------------1----------l----------t----------l----------l----------l----------l----------l-----------
PERSONS WITH COt1PUIHTS I 9 I 10 I 9 I 8 I 6 I 5 I I lit
I f 15.87.1 I C 17.57.1 I I 15,87.1 I I 14.0Y.I I I IO.SY.I I C 8.87.1 I I f 2ft.6Y.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsoNS WITH NO tONPUIHTs I 4& I 47 I lt8 I 49 I si I sz I I o
I c 81t.2x1 I I 82.51.1 I 1 ~.21.1 I c 96.0Y.I I c 89.51.1 I c 91.21.1 I I f 75.4:0
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH NO OAT& I O I O I O I O I O I O I I D
I , o.ox1 I c o.ox, I c o.ox1 I c o.oY.1 I c o.ox1 I c 0.01.1 I I I o.or.1
0
0
"'OIi
~
Table 4
PATIENT COlMT "AXl"--1 TEHPERATUAES
RECCHUNANT HEPATITIS B VACCitlE
STUDT 1795
TREATMENT
lOT NUteER CK564
OOSE 10 MCG
PATIENT CUSS HEALTH CARE PERSONNEL
I TOTAL VACCINEES I 148 PATJEHTSI - DOSE 1 I

1---------------------------------------------------------------------------------------I
I . DAYS POST VACCINATION I NIJff!ER
HAX TEMPERAT\RE
10£6 , . ORAL)
1---------------------------------------------------------------------------------------I
I O I l I 2 I 3 I " I S I I I ttAXWITH
TEMP
••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
< 99 e9
• 87.]lO I 90 I 911 I 100 I 101 I 96 I I ea
I t 91.67.1 I I 93.3%) I t 96.27.) I 000.07.1 I I 99 . 0,0 I I I 80.T/.I
I I I I I I I
99 - 9'.9 I 13 I a I 1 I 3 I D I l I I 19
12.77.1 I I 7.57.1 I I 6. 77.1 I I t. 97.1 I I 0. 07.I I I 1.01.1 I I I 17.<tY.I
I I I I I I I
100 - 100.9 I 0 I l I 0 I 0 I 0 I 0 I I 1
t.07.1 I t 0.9,0 I I o.o:o I c o.or.1 I c o.07.l I t o.o;o I I I 0.97.I
101 - 101. 9 I o I o I o I l I o I o I I l
I t 1.0:0 I t o.o:o I I o.o,o I t 1.or.1 I c o.07.l I t o.o;o I I I o.9Y.I
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TEt1PERATU!E TAKEN I 102 I 107 I 105 I 104 I 101 I 97 I I 109
I I 68.91.I I I 72.ll) I I 70.91.1 I I 70.3)0 I I 68.2,0 I I 65.Slf.J I I I 73.6,0
------------------------l----------l----------l----------l----------l----------1----------I---------------------I-----------
TEl1PERATURE HOT TAltEH I "6 I "l I "3 I ftft I 't7 I SI I . I 39
I I Jl.llO I I 27.71.1 I I 29.llO I I 29.77.1 I I 31.87.1 I I Yt.s:o I I I 26.47.1
0
0
"'-0
u,I
Table 4 (cont)
PATIENT COll4T HAXIt11J1 TEHPERAT\JRE9
RECOHBIHANT HEPATITIS B VACCIHt:
STOOY 1 11,s
TREATHEHT
LOT M.lt18ER CK564
DOSE 10 11CG
PATIENT CLASS HEALTH CARE PERSONNEL
I TOTAL YACCIHEE9 I 146 PATIEHTSI - OOSE 2 I

1---------------------------------------------------------------------------------------•
• DAYS POST VACCIHATIOH • HUHl!ER
HAX TEMPERATURE
IDEG f, ORAU
•---------------------------------------------------------------------------------------1
I I • l I 2 • J I 4 I S I I WITH
I HAX TEHP
······················-•··········•········•·1••······••1••········•········•·1••······••1••······••1••······••1••········
I • I I I I I I
< 99 I 64 I 70 I 71 • 69 • 611 I 63 I I 60
I I 117. 71.1 I I 9l. 3)0 I I 94. 77.1 • I 94. 57.1 • I 95. 87. J • I 94. 07.1 I I I 711. 9l0
I I I I I I I I
99 - 99. 9. • 9 I s I 4 I 4 I J I 4 I I 16
I I U.J?,) I I 6. 77.1 I I 5.37.1 I C S.57.1 I I 4.27.J I I 6.07.1 I I I 21.1:0
------------------------l----------l----------•----------l----------l----------1----------1---------------------l-----------
n:nPEHTWE TAKEH I 73 I 75 I 75 • 73 • 71 • 67 • • 76
I c &o.or.1 I I Sl.47.1 I c s1.47.I I , 50.01.1 I 1 ,11.61.1 I c 45.97.J I • , 52.11.1
------------------------l----------l----------•----------l----------•----------•----------•---------------------l-----------
n11PERATURE HOT TAKEN • 73 • 71 • 71 I 73 I 75 I 79 I I • 70
I I SO.OX) I I 411.61.I I I 411.61.J I I 50,01.1 I I Sl.4XJ I I 54.1:r.l I I I 47.9?.I
0
0
1\1
J::
0
Table 4 (cont)
PATIENT COlMT HAXIHl.t'I TEHPERATUAES
RECot18IHAMT HEPATITIS B VACCINE
STUDY : 0795
TREATNEITT
lOT Hllt113ER I tK56'4
DOSE : 10 NC&
PATIENT CLASS: HEALTH CARE PER~EL
I TOTAL VACCIHEE9 C 126 PATIENTSl - DOSE l I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I HlfflER
HAX TEHPERAT\JltE
I DE6 F, ORAL l
1-----------------------------
I O I 1 I Z
·
- --------------------------------------------------------1
I l I It I 5 I •
WITH
• IIAX TEHP
•••••••••••••••••••••••••••••••..•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••••••••••••••••••••••••I••••••••••
HORHAL I •
O. 01. l (
l
2.37.l (
1
Z.37.1 I
1
Z.3i0 (
1
Z .'41.1 (
1
Z.'41.l I
0
0,07.l
< ,., 36 37 1110 0 38 39 38
• 87.8lO I 84.1'0 I 90.91.I I 97.71.1 I 9D.SiO I 92.97.l I 79.27.l
99.9 3 z z z 6
99 -
•• I "
9.8i0 C 6.8lO C 4'.SlO C
0
t,OY.I C 4'.&iO C 4'.87. I I 1Z,5lO
I
100 - 100., I 1 z 0 0 l 0 3
Z.telO lt.SlO 0.01.1 0.01.1 Z .41.1 0.01.1 6.]iO
101 - 101. 9 0
C
0
C
1
' 0
C
0
C
0
C
0
• o.ou I 0.0lO C z. 31.1 C o.o:o C D.01.1 t 0.07.1 I o.o;o
102 - 1oz. 9 I I I l • 0 I O I 0 I O I • 1
I C O.OiO I I Z.37.l I I 0.0)0 I I e.01.1 I C e.01.1 I ( 0.01.1 I I ( z.11.1
------------------------1----------1----------l----------l----------l----------•----------•---------------------I-----------
TEHPERATURE TAKEII I U I "" I "" I "" I te2 I 42 • I 48
I I 32.5iO I I Yt.91.1 I I 3".91.I I C 3'4.97.1 I I 33.37.1 I I 33.37.1 • • I Je.un
------------------------l----------•----------l----------l----------l----------1----------1---------------------•-----------
TEHPERATURE HOT TAKEN I 85 I az I az I ez I e, I 8" I I 78
I c 67,51.1 I I 65.UO I C 65.11.1 I c 65.17.1 I c 66.71.1 I c 66.71.J • I c 61.9Y.I
0
0
rv
-
b
Table 5
PATIENT COUHT "AXll'AJ1 TE"PE~A~ES
RECOMBINANT HEPATITIS B VACCINE
STUDT 0795
TRUTMEHT
LOT HUtlBER Cl215
DOSE 1 10 nee;
PATUHT CLASS: HEALTH CAIi! PERSONHEL
---- ·-----------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIH£ES I 97 PATIENTS I - DOSE l I
l---------------------------------------------------------------------------------------1
• UA~S POST VACCIHATIOH I H'.nER
"AX TEMPERATURE
I DEG F, ORAL I
l---------------------------------------------------------------------------------------1
I D I 1 I I! I J • • • 5 • I
WITH
I HAX TEHP
••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••••••••••••••••••••••••••••••••••••••••••••••I••••••••••
I I I I I I I I
< 99 I es • 90 I ee I ,o • 89 • es I I eJ
If 92.41.t I I 93.8)0 II 91.7l0 If 95.71.1 I I 95.71.1 I
I 95.51.1 I II 86.5i0
I I I I I I I I
99 - ,,. 9 I 6 I , I 7 I . J I • I J I I 10
I t 6.s1.1 • f •.21.1 I , 1.1;0 I , 1.2x1 • 1 tt.1:0 • , J.tt:o I I c 10.•r.1
I • I • • I I I
100 - I oo., • l I Z I 1 I 1 I o • 1 I I J
I I 1 .11. I I I 2. llO I f 1. 01. I I I 1.11. I I I O. 01. I I I 1. 11. I • I I J .11.1
------------------------l----------t----------l----------l----------l----------l----------•---------------------I-----------
TE'1PERATURt: lAl([N I '2 I 96 I 96 I 94 I 9J I 119 • I 96
I c M .11x, t , 99. 01. , I , ••. o:o I 1 96. 91., I 1 95. 91. 1 • t 91. er. , • I c 99. o:o
------------------------I----------I----------I----------I----------J----------1----------1---------------------I-----------
TEMPERATIJRE HOT TMEH I 5 I l I l I J I • I 8 I I 1
• f s.2z1 I I 1.01.1 I C l.Ol!I • C 3.llO I I •.11.1 I I 8.2;0 I I I 1.01.1
0
0
IV
~
IV
Table 5 (cont)
PATIENT COUNT HAXItw.Jt TENPEAAT\JRES
REC01BIHAHT HEPATITIS 8 VACCINE
STUDY 0795
TAUTHENT
LOT HUN8ER CLUS
DOSE 10 11CG
PATIENT CUSS HEALTH CARE PER~l
-----------------------------------------------------------------------------------------------------------------~----------
I TOTAL VACCINEES t 97 PATIENTS, - DOSE 2 I
1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I ~ER
1---------------------------------------------------------------------------------------I
NAX lEHPEAAl\JRl
t DE& F• ORAU I O I 1 I 2 I 3 I ' I 5 f
........................•..........•..........•..........•..........•..........•..........•.......... I
, , NITK
.......... I .........
I
NAX TENP
.
< 99 I 71 I 7~ I 75 I 75 I n I 12 I I 67
93,4)0 I t 92.SY., I t 93,87.I I I
I .... 97.J I '1.2i0 I I 91.llO f I I 83.77.,
I I I I I I I
99 - 99.9 I 4 I s I 4 I 4 I 6 I 6 I I 10
s.Jxt I , ,.1z, I , s.ox, I r s.1z, I r 1.sio I , 1.,1.1 I 1 , 12.sxt
I I I I I I 1
100 - 100.9 I o I l I l I o I l I 1 I I 2
•. oio I , 1. 2z t I r 1. 2x, I r o. o:o I , 1. uo I 1 1. Jio I 1 1 t. sx 1
I I I I I I I
101 - 101.9 1 1 I o I o I o I • I o I I l
I , 1.JlO I r o.ozt I , o.oio I r o.o,o I r ,.oz, I t 0.01.1 I I c 1.2z,
------------------------l----------l----------t----------l----------l----------l----------1---------------------1-----------
TENPERATUAE TAl<EN I 76 I 80 I 80 I 79 I 80 I 79 I I 80
I t 1e.c.1.1 I t e2.s1., I I et.sz, I t e1. ..:H I t e2.s:o I t a1.ttu I I t H.s:o
------------------------l----------l----------l----------l----------l----------l----------1---------------------1-----------
TENPEAAT\JlE HOT TAI\EN I n I 11 I 11 I 1e I 11 I 1a I I 11
I t n.61., I t 17.57., I I 17.57.J I I 18.67.t I t 17.51.1 I t 18.61.J I I r 11.s:o
0
0
N
b
"'
Table 5 (cont)
PATIEHT COUHT HAXIMUtt TENPEAATURES

RECOl18IHAHT HEPATITIS 8 VACCINE
STUDY : 1795
TRUTHEHT
LOT NIJt18EA : Cl2lS
DOSE 10 11CG
PATIENT CLASS: HEALTH CARE PERSONNEL
I TOTAL VACCIHEES C ci4 PllIEHTSt - DOSE 3 I

1---------------------------------------------------------------------------------------•
• OAYS POST YACCJHATIOH I tu18ER
NAX TENPEAATUlE
I DEG f, OAll t
1---------------------------------------------------------------------------------------I
I O I 1 I 2 • J 1 ft • 5 I •
WITH
• HA)( TEHP
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l•••••••••••••••••••••I••••••••••
I I I I I • • I
u I
< 99 I
I
I
38
C 88.ltiO
•
I
I
'40 I ,.,. 1 39 I 39 •
C 85.liO • I 87.2iO • C 95.71.l • I 88.6)0 • I 86. 7X) I
I I I I I
I
• 38
C 80.97.1
99 - 99. 9 I 3 I 6 I 6 I 1 I :J I te I I 6
I c 1.0;0 I c u.e;o I 1 12.e;o • c 2.2;0 I c 6.&i!l I c 8.97.t • I c 12.ex1
I I I I · I I • I
100 - 100. 9 I 2 • 1 I o • 1 • 2 • t • I 3
I c 4.7i!l I c t.llO I I D.07.l I c 2.27.l I C 4.SXJ I I lt.tt7.l I • I 6.'4iO
------------------------1----------1----------•----------I----------I-
TENPERATURE TAKEN I '43 I 47 I 47 I 46 I
.--------1----------1---------------------I-----------
4'4 I 45 I I ft7
I C 45. 7i! J • C SD. 07. I I C 50. 07.1 I C 48. 9)0 I C 116. &i! I • C lt 7. 9X I I f C 50. 07. l
------------------------l----------l----------l----------l----------l----------l----------1---------------------1-----------
TEHPEAATURE NOT TA~EN I 51 • 47 I 47 • 48 I 50 I 49 I I 47
I c s,.'3?.J I c so.o;n • c so.07.J I c s1.uo I c 53.27.1 I c 52,1:r., I I c so.ox,
0
0
"'
~
C
0024'5
IAT-U..10
CIJNICAL EVALOATION OF A llECOMBrNANT HEPATITIS 8 VACCINE
F. Deinhardt•, W. Jllc, 0. Zoulek, B. Lcrbeer, and B. Wllske
Mu von PtttenkoCw·lrstltute, 1000 Munchen 2, W•tern Germany
Thirty healthy, younr volunteers rr" or any HBV markers were vaccinated with a reC!Ombinant
hepatltil B YacclM prepued by Merelc, Sharp at t>ohme, W•t Point, PA. Ten \C HBs>.1 were
administered Intramuscularly at time O, and OM month later. Set0e0nverslon rat• and reometric meao
00nccntratlons alter 1, .2 and 3 months w.-e compared with an ace- and sex-matched control croup
vaccinated with 20 \C or plasma derived vaccine (M trek Sharp & Dohme) (Table 1).
Table lz Comparison or Immune r•po,we alter recombinant vaccine and plasma derived
vaccine.
month anti•HBs C,eom. n,un)
11110
reeombinant plasma recombinant pluma
vaccine Y&C(!lftt vaccine vaccine
1 2T 44 I.I 15.2
1 TD ts 3'1.1 52.S
3 IT ts 21., 164.4
ln the recombinant vacelne pup, 31" or the total &nti•HBI at month 3 wu directed acalnst the
detwminant a or HBIAC, compared to 301' In the control croup. No lncreue In antibody titers against
candJda alblc'int wu found In recipients of the reeombll\ant vaccine 4 weelcJ a1ter the second Injection
u compared to prevaccinaUon levels. No aerlo• side errecca were observed In any or the vaccinated
indi viduala.' ·
Deinhardt F, J11g w, Zoulek 6, Lorbeer 8, W11sk• a. C11n1cal evaluation of 1

· recombinant hepat1t1s B vaccine. ln: Vyas 6N, D1enstag JL. Hoofnagle
JH. eds. v1r1l Hepat1t1s and Liver D1se1st. or11ndo:6~unt and Straton,
l984:H9.
002Qb
1174 TKllANaT,NOVVGU.2~984
~CAL EVALtJAnON OF A RECOMBINANT TAIU 1-IIX AJID AGI Dllfflll.'T10N MTHI no YACat.ATIO!,
HEPA1TI1S B VACCME GIOU,S•
T•II "-- MIit

1.1.0UIP
W.JU.G
M.Sol.WDT B. "111.JJtZ No A,eC,,) No A11lorl So .,,.,~,
G.Zo\TUk F.DIINIWDT ■-1111•..aillll I) J4•hJ•I 11 k·taM IS 21·ltl· ~
Mu - ,,. . . far-,..., lUlll/0 Mildn .\ · -·a.-,, ...._..,;,,~.,.._. (2l•M)
41 2'·hJ•7 n
(21•M) (25•11)
k·TaJ·O II 2S·taZ · >
.s.,,,._,,, Re=mbwm 11,pawil I ftCCUIC pnpand
(Jl•J2) (21•S2) <2'•U)
from awrm apraud in rem -siwn 10
30 hallhy JOWi& volwirem. ScrOCDIMl'lioll 11111 IDd 111ti-
v--.
Hls lffda
m■ched fo, •e
WIN mmpll'ld witJI dlaec ill • COCltrol poap
IDd eca no ud reccmd ~
bepeti1il I ncc:iDc. 4 Wtdll after tbl dlird imlmmilltioe
TIii • h:iow1 -,.ilia
I ftCdM - prcpa-cd by Merel
Sharp fl Dalla .-.n:h llharllorils (let 9WCJ 625). II COllliau
raultS were limiLv iD tbl cwo pvupa. la die .-billlllt o( pwilild HIIAa. ....,,. .... pradumd iD l'KOlllbinanl
nccine ,roup the immw NlpOGM dndoped mon slowly S .nili« 111d abMrbed • llllllliaium h)'dtosicll. I 1111 of W1Ccine
durin, dle •11 phlle and .lffllCD1111'1nion me llld maa _ _ . ,o,.olHIIAf. ,.__flCCiDr_lllolllbtypla(lac
anti•HI• lc¥cla were llipdy lower ill -..la; lbil probably 77Sl901•21 CF U2•2 McrdlSharplr Dlbme~ Subjccu ill tJw ltlldy
rellcr1 Ille or or
I lowtt dcllC ,-binlllf na:iDc ( 10 Ill .,_, nail'lcl JO 14 .r_..__,-=-..,_.,,, • 0,
CDCDpltCd ,ritb 2014 oftbl plama YICCiDc). SidNO'cu were I, ad 6 .-daa; lllabilCII ia 1111CMl1"ll.,_,nai,,d2014 ol'
1li&ht IDd IIIU°bod)' til,- 11&1111 w.U. •lbia,u WIN DOC pl- dlliw.d ftCl:iM • dis - ialemla. (Since tbc
mamed in RCipicms of tbc •KIDIDbiDam ncc:iDc. r t iullt ftl:CiM - - • willlfmlia llllly, 11111 Diil nb
PIPliA .... ..,.., ii - iaitially tlloupl to hc - ~
dim die plama ww:ciM.) IIGad 1111Dpia - • Ilk•• tbe dl7 of
lall'MllcdN die finl ~ ud dim aadlly. Subja:a wn Ilka to kctp
CUllU1''T kpacitil B YKQDCI SC cfl'IClm 1114 ..Cc.' •Ir,_. tlhDdf
ad! iD;.aieL
llmfll'II••
lllcl tidHll'cts f• 5 cla7' after
Howe,,1r, bsluM tilley •• pnpvld ma pillml o(b11111111
~•iris B viNII c:uricn, supply ii rauictld by die IIDOIIIII
of plaaml available and br tbc CDlt ofpurifyina the bepatitil B ~
1urf1a anti&c (HBIA&) io racier i& free from bepailia B HBIAI, Mli-lB&, 1114 •i-Hlc - · Nlltd by radioi_ll_
Yinas encl ocher poasiblc imcaiou qam. Tb111, co 1DCCC chc -.y widl ~ l y ll'flilablt kill ('Al'SIUA U', 'At'SAI',
worldwide Deed (Of bcplrihs B ftCCiDc, 11ft - or 'COi.Ai', Allllall Laboraarill). Aati-HI& _car,aiom in It'll
. ., alculltcl llJ die mcdlOcl otHolliDpr 1111.• lhl linl 'CHO
p,cpamiaa lff rcquind. Liedy, fttlon Clff)'in, the DNA
tcq\Mllc:,c for HBIA& wae prepared' and tbe amipll WII " ' - pnpar■iclll 1m 111ma ...sill, cliluliDo or 1:400.'
apreued ill tbc ,att s,,..._,- ,.,.,.,;,_ 1 Ywr cdls . _ _ S _.,... Md C al,._ Ule • - mriJmic
dllniiulls,1 atillDdill epiul C .,__ _ , ell'lllined ~ -
assemble tbc HlsA1 polypcpcida ilno ,-,ida IUllillr ro tbc , - i w ~ ia 26sullilm• cllJ0IIICl4 neb af1cr
22 nm panido found in bWIWI plllma; ,ast HlsA1, tbt-4 IDd tllircl illimiaafll..__, WICCiM. Saa'"''"
bawt'ftr, wililte hWIIIII HIIA& ii DOt l,IJCDl1bred. A nccim ~ r. asillodill epiaa die dn•lliAMI • of HB1A1 a
developed fi'om yasr HBaAa ailnullled mullody
production ill lllict, lriffl moatera, - ' cbimpamea; IDII
wbcn Ya:Cilllrc dlimplDIICI ..,, culJapd wnb bllllllD
bcperiria I Yirlll of cWfnm sabrypll, dlC)'.,.. CIOIBpllltly
procmed! We aow rqian die immllllimioll ot JO hakby
pnrioa!J dacrillecLt
.....
Scrom11ftrlioa me 111d man 1111i-HBs levels clurin1 1he
courv of'immlllliarion •c abowa in table II. 1nc immune
,oun1 ¥Vh&m_, with rJae fine laeplU&il 8 Y1CG11C produced rllJIOIIM in dlt rcombiuDt ncciDe poup •-u ltu
by recoaibi.uar DNA rclmoloff. pnmoWIClld charina the &rm monw chin in w plama
ffCdat poup, • tbl,11"11 by lower moc:onvusion rates and
lower IDClll lllli-Hls lfftla. Tlaac diff'erencn became non-
$4,6,iat aipiticuc after tbc woatcrdoac 111D011th h.-h11129out o(30
111bjecr1 (97"-) wwrt mi-His poaitift (control, 41 ou1 of 41)
JO haJt11y IDldical audrals and labarll-, ,...,. wwe ltudied with 11to1111Clric man anti-HS. lffelo(2U5 ll:/l(con1rol,
(17 rcmaic. 1> 11111c;- • ' 25:a:J -,r, rm111 21•>4). Sullicr• ia 4299 IUII). All anri-Hla-politm indiYidlllls in rhe
tJwma1rol src,upllad i.m ~ w u pbm ~ndna:iac
ill III arlilr •udr, 5 dlcJ _, 11111dlld "1 ... Md - • tbe 1tlllly rcombinam ftCCille IJ"MIP ud 111ti-HS. vah111 above 10
sro11p (t*ll 1). ldcrr 1'SCUl&iocl, Ill lllbilnl - • ....ift for
JtJII. 2 (6· 7') were low t■ponden (mti-Hls btlo..- I 00
HIIA&, lllli-Kla, ancl 1n&ibDdio lpilla lllpa1iul I can 1111ipll IUII), J (l°') were micrat4iae _roponcltrs (anti•HB,
(lftU· Hlcl, 1111d caeir __.,..,._ _ ""'' _ , - - (lllniM 101-1000 ltJ/1), and 22 (73• Mlil were normal 10 bash
and •Pl"•• ainolnnefer-,17 _,Cit IUII, -ps,i,,clr~ rwpoodcn (IDti-Hla paacr tblJI 10001\1/1). Similar values
J11g W, Schll1dt M, Zou1ek 6, Lorbeer 8, W1lske I, De1nh1rdt F. Cl1n1c1l

eva1u1t1on of I recOlllb1nant hepat1t1s I v1cc1ne. Lancet 1984; 2:1174-5.
00247
THEJ.ANaT, NOVEMIU.24, 1914 1175
TAIi.i 11-IMMIM IISPONIIS Al'TD VACQNA T10N 111bjecti im1111miMCI wilh I llllliler doR (51,11) ofconventional
s----c•1
.....,,.... An1i-Hlt (TVIQ" nccinc Oil& \V, Zathoval It., Schmidt M, Deizi.h.vdt F,
wapubliabcd>, aod llll1 ,en.a the - of uullcr CllOWUS of
-- --•
Ultipsa. Amipll cootcm of bolh NCU1bimn1 nccinc and
"-"
~
-=-
(II • JD) (••41)
._..... ......
,-...
........ ,t
plaml-dcriwd vaccine is daermined • HBsAa protein. Tbe
nccifta arc prvdut"ed IDcl trcatal diff'crmdy, bowevcr;'·'l
lheraott limilar procciD CDDtmc doll DOI DeC'ISUfily mean
I
,z
•s JlfllJ
• (77]
21 ('JO)
a r,.)J
,. ,.,.,
II(#)
,.,.,.,
Jf 1115)
'
2' .
,m,,
IS <O·OS
<O•O,
<O•O,
aimilar immUDOSCDicity. Tbc Jml and pwina dcrivtd
HBIAJ differed in raaivity ill ndioimanuno111ay tests; tht
• a2'""
ll (UJ
flJJ
IISJ
1111
Jt
Jf "
:ms
41 (IIOI
m
.
6J
a&J
u,t
<O•O,
<O•M
<O•O,
>O•O,
raetiffly oftbe HBaAs prochacltd iD ,all •-u only 20-5°°"
oftbt rcactiviry of plnmt-Clr;ved HBL-\1.• Thm, v.•clsht·
for•wci&m tilt immUDOltllic:iry or tbe recombinant ,,.c:cinc
0
'
Aai-Hl1il,-• IMa-,c_ill_,....,alJ.
scam to be 1111 dam daal of the plasma-derived vaccine.
ADocbcr apllDllioa for tbe lower immune response may be
t ............._ ... dm 10111 orrsombimnl ncciac waa pvm per lin1lc dose
TAILI 111-IIIWl.""'I UPOMIIS DI MALUAHDIIMAUSIAFTD mmpand witll 20 14 of plama-deriwd nc:ciDc. A hi1hcr
.......... dolc(20or 401C)oCilac recombilwlt nccmc wvv.ld probably
--...
T1l&D DIOCUI.A~
Ii" die 111111 rllUla • lhc plmu-4cmcd nccinc.
- •...... •
I
,. Despite &bl llipdy loWII' immwairy 1daiend with the
nmmbinw YICCinc, procaiota will probably be • 1ood u
Meis wilh dac CIDll'ftDtiollll 'IICCinc, iD tlaat all 29 1ubjeas with
S..--niaNt WIJ,-J 1111,,,. .
Alll>Hl1 (roll)t Ill <O·OS
dctecsable mi-His bad ..iue abcm lhc prouction lcvd or
10 IU/l. 11 ID 73"-, anti-HI• Inell after me third ncciaation
,...... were man &baa 1000 RJII; dala Illa bla lbown to r,11ran1cc
S..-Wnia~ IT/l7 (II. JSl2J(I. . pcnillme1 ofaa~HI• abo,w tbe pracctivc limit for 11 lcast
~HI, (Jt:ll)t :1212 -.0 >O•O,
3 flll'l- 14 ID ldclitiota, all aubiects wbo acromavencd bad
~-
•r._.,,..._..,
ti,....,.,1.,;.,u..,.......__ ....... ..,.11111...,.
were obtained ill die CDmroJ poup. AJtboup tbe immwie
wibodia apiDII lhc CDllllllOD clncrmimat • of HBs.a.1,
iDdicltiq a.-proccaioa qaiNt infCC1ioa1 with other
subtype of HBIA1. Side-cfrec11 .t'tcr tbe recombinant
ftCCiac were Dllliaible IDd clid DOC diff'et &om tbose
oblclffd aft• planm-dlriwd YICCiDc. nae 1bacnc:e ofa rise
rapome,UI lbe two vaccma wae similar lf\udle Ml CO\Ult ill mtibadia 11limi C allia111 indicate wt no aou•
or immulliuuoa, rapoma or mall 111d f'cmale IUbjecta fC:IClilll ,,_ umsaaa wen praau ill lh1 YKCnc.
dilrcred. In both ,roupa aD the WCIIIICD lll'OCODffned and &bl S't1a-MnU..SellrwatflfaptnncMial--•·
1eomeuic man anti-Hla Inell did 11111 dilfer lipificudy Ca. O ......................... J.Mu,r. PffluuCtt•IUIINt,
(3212 IU/1 \II 4640 IU/1). H4"l'fflr, ill mai. recaYiDs Pm t •sw.t•IDCIOM..... 2,T•CiinaaJ•
rccombimru nc:ciAe die IGOCDftvcnion rile . . 92' n
1009., and tbe pomctric mC1D uw-Hla . . 911 .,. J894
run (table w~
,__ a&nlD'CII
1, 0 . . . f, ( - , f t l - - - A • I ._ _ _. .. Cao In ltll; If:
PrdimilWy tau indiclle dllc ftc=lbium na:iac, lib
die pJumHcri91d nccuic, iDduca miboclia 111iu bodl
lhe • aad tbe i CDmpoamtl oC Hla amipn. Ali• monda ],
_., ............. _,,_.,......,. ............
l.\'-P,Go.,P,O.-.,M. ....... l,GeoamNN.....,'11 S••INI•
N - ,.,.__, 11 ► 11 .
J.V-P,..._A.._1r'J,.w....G.KdlD.~
...,..., _ _ _ _ _ _ _ _ , __,-... ,111•
. .- •ti
., lf~-,o
abo111 31-r. or me tou1 asi-Hla ,,. dinaed aaliml
daermiaar•. N_.,_,_._
U. .._.,_ __
f . MIAllll 1r'J, ..,_ 'lr'J. M-•
12. .-__, DL Molln
,._,-..1111, 1r1-to
.- il.
No impanut lidN!'ecu wee obMrffd after
immwaiutioG wilh &bl rfCWlhinm• na::iM. Miw local
aympcomsaudaaulllliem paira,ilc:bina, bunaiac,aclllisln
""1liq ar tbc illjectioa lile wn npanld aft• 24 ortbe 90
injcaiom. OD • ocaaioa did bocly 1mpcncun rile lbow
37·9•C.
1. Lc-R,J,laW",1-,L-M.n......P. P_ _ ,.. _ _ ,_
............ ,,..,, .......... ,11-1,.
. . _ . , 1191
ltU: f t l -
t . _._.. .._..Oil-._ .
rllO ,_.._ Joo••III: 1m- JI
I.T--,.T........1,·."-'lluL ....... - . - ...
-4
, ........ n._L.....,.D......,JL. .._.•..._•a,.:c,.. .,,
..._...__,__..,'-Ila
,._ - ~ - a . . . _ W', - NJ. II."' ,·.,,,
lat•v1t Pr11,.
..,.,_.c.,oJ,~
0( 26 111bject1 t•ttd, Ill bad mcibodia ll■DII C tUNrtl kT----C-..r1~•-r,1,__,,.,.,aru.
T•i■: i--M-,.r...._,., , 14-JI
on day O(tirra mnn l:IO to l:)20)and1irra did 11111 iDcrase • .Jill'lr',DoaiowC.0-. P. R '--AJ, ,____,,11vGJ .
after imml&Diutioll. ......_ a, 0...., lA. . . . _ I
wfan - • • 1Ha....., ,..,..._
_.,...
.,._,._ • ...,.,.,..._...,_..,..., ,.- ,·...,,t1,.u,
Duc...a.. It. 9-W',.,_CLZ-IA.lwt,y 11.~A.A,_,....,.,..._,u,.,.,.
.. ....,.,.,..._,_•.._,~,. .......... ,,__,, ,,11.
Tlaret doles or 101,11 rteombiamt ..,_ilia I \llmDC pn a.m-a
11roconvcnioo m• ud pomctric au aati-Hla Inds JI. C.
:-.,_
, ........ c - ................,...
, .....P,_ _ _ , _ , _ _, _..,,W ■..ia1r
_ tlat;z.elllol 1(
aimilar 10 I.boll iDctucitd b)' lhnc .... or 20 .,, , ...... , . _ ,.. , . ~tl► M .
derived nccine. Tht rllllla wen aJao comparable wilh I.boll IJ ........ ML~, II, M,..., 1r'J,MtLaaAA. •--•"I•·"''"'
--
obtained iD llr1e trials or coaYCDCiooal VICCiaa. ,.,,. a., ""-'■a L ...._. I. .. 11• . .
.............,, ...... ...,60....lrsn
el.,._... '-•""' .,,
al., .. , IJD-lt
ll.C.....•A.C:....,.P.... P.•11-,.__.n..--1 .. .,,..,...,.,,.,..
,._ ............. ,. :
Tile immune rapoDK to the recoaabiulll 'flcciac.
bowev1r, WU lcaa lltoGI duria1 &bl arly pblle ( l ◄ IDODllat)
in all subjcaa, and ill awa mean 1mi-HB1valu• were lower
...,,._
__
. .-
' - · ,.,_..._
• - la: .......... . ~NJ . ......... Jl,NI \ 'w•1• .. ••11111
·-~
14 J,lsY,a.-M.Z..-a,.,..,..._,, ,.._ _ _ ,.,._"'"•••••
in the recombinlnc sroup c,,ea after tbe mmplae coune or ....... I-Olau-...www,._.----. ..... Mt,-••l lhv•~ifJll1o••
Ullllll&Diulion. nae rlll&lu IR CDmparabl1 with r&lldinp ia
00248
Edward M. Scolnick. Arlene A. Mclean,

David J. West. Jules L. Dienstag.
23
Antibody and Clinical Responses Among Healthy
Recombinant DNA
Currently. all commercial hepatitis B vaccines are comprised of HBsAa purified

from the plasma of human carriers of the virus. However, the use of recombinant
DNA technoloay to effect synthesis of surface anti,en by a culture of microorpn•
isms is an attractive alternative to infected human plasma as a source of HBsA1
for vaccine. Good e1tprcssion of the ,enc for HBsAs has been effected in yeast
(I).
Recently, anti1en purified from fermentation cultures of a recombinant strain
of the yeast, Saccharomyc,s c,r,visia, containin1 the sene for the adw subtype
of HBsAa was rormulated into a vaccine through absorption on alum adjuvant.
Two methods were utilized for the purification or the HBsA1. lmmune affinity
chromatoeraphy uses specific anti,en-antibody bindina to effect purification, while
the second method, hydrophobic interaction chromatoaraphy followed by ael
exclusion chromatc,sraphy. depends upon the selection or water-immiscible mol-
The physical and chemical characteristics of vaccine made from HBsA1 pro-
duced in yeast are very similar to those of vaccine prepared with HBsA1 purified
from human plasma. Funhcrmore, the yeast recombinant hepatitis B vaccine has
been shown to be both immuno,enic and protective in animals (2).
We report here the clinical and antibody responses obtained in the fint three
human clinical studies of the yeast recombinant vaccine involvin1 a total or IOI
\IIIW. HEPATITIS and LIVER DISEASE Cop,,rigttt O 118' bv Grune• Stnnon

ISBN NOl9-117&-5 All riohll of l'9P'Oduclion in any form merved.
Scoln1ck EM. NcL11n AA. Wist DJ, D11nst1g JL. lilatk1ns E. Dt1nhardt F.
Antibody 1nd c11n1c1l rtsponses ..,ng healthy adults to I hep1t1t1s B
vacc1nl •d• by rtcOlllb1n1nt DNA. In: Vyas &N. D1enstag JL. Hoofn1gl1 JH,
eds. Viral Hepat1t1s and Liver D1s1ase. Orlando:&rune and Stratton, 1984:
315-11.
316 ~olnick.. Mclean. West. et al
vacc:inees. Participants were healthy, nonprecnant, adult volunteers. At entry.

subjects were neptive for all hepatitis B serologic markers, had a nonnat ALT
level. and had not received any other hepatitis B vaccine.
Participants in the studies received a 1.0-ml intramuscular injection of the
yeast recombinant hepatitis vaccine containin1 JO IA-& of HBsA& at O. l and 6
months. The vaccine used was from one of two lots. (Lot 93'4 prepared by the
immune affinity chromatosraphy method and Lot 972 prepared by the hydrophobic:
interaction chromatosraphy method.) Vaccinees were asked to record their tem-
perature daily for S days after each ittjection of vaccine and to repon any local or
systemic ructions that occurred durin1 that period.
B serolopc marten and ALT. In addition, a mioimmunoassay for the detection
of antibody to anli1ens in an· cxtnct of' yeast lackin1 the acne for HBsA1 was
The vaccine was well tolerated. 'There have been no serious adverse effects
attnbutable to vaccine and no evidence of hepatitis B inf'ection amona the vaccinees
(i.e., no elevation of ALT and no antipnemia). Local reactions consistina prin-
cipally of mild soreness at the irvection site. senerally lastina 1-2 days, have been
reported followina ~ of iruectioas with vaccine purifted by the immune
affinity chromatc,sraphy method (Lot 93'4) and 169(,..2'9' of inject.ions with vaccine
purified by the hydrophobic interaction chromato,rapby method. Systemic com-
plaints inc:ludin1 fati,ue, headache, elevated tempcratun (JOJ• F-1or F, oral),
pstrointestinal disturbance, symptoms of upper respiratory infection and nose-
bleed have been reponed followin14~339' of injections (Table 23.1). There have
been no sianfficant increases in antibody to anti1ens in yeast extract associated
with vaccination.
Table 23.1
Clinical Responses amon1 Healthy Adults to 10 ..., Doses of
Recombinant Hepatitis B Vaccine Administered at 0, I and ,
Months
Proponioa ('ii) or Vaccinees with Clinical Complaints
within, Days or Vaccination
Study# Vaccine Lot # Site Dose I ('ji) Dose 2(~) Dose 3 (~)
T79 934 Local 12/15 (IO) 11/U (73) 11/1.5 (73)
Systemic 5/15 (33) 3115 (20) 1/1.S (7)
972 Local 6'24Wl l/19 (16)
Systemic 1/24 (4) l/1~ (16)
792 9),4 Local 19121 (61) 11/21 (39)
Systemic 5121 (II) ~an•>
795 9),4 Loca.l Y,J(20) 6119 (32)
Systemic 5125 (20) 1/19 (5)
00250
HBV Vaccine Made by Recombinant DNA 317
Table 23.l
Scroconvenion Frequencies for Anti-HBs antOftl Healthy Adulu
Re1:eivin1 10 f,1,1 Doses of Recombinant Hepatitis B Vaccine at 0, I
and6 Months
Proportion (9') ofVaccinees with Antibody
Study# Vaccine Lot # I Mo. 2Mo. 3Mo. 6Mo. 7Mo.
779 &IS 1411.5 15/U 15/U

934
(40) (93) (100) (100) "'''
(100)
972 1n., 13/19 12/14
(29) (61) (16)
792 934 11/21 21/23 13/ll
(39) (91) (100)
795 934 l/30 21/30 19122
(27) (70) (16)
Antibody responses lO 10 1,1,1 doses of the yeut recombinant vaccine have

been comparable to those observed in previous studies with 20 l'C doses of vaccine
prepared from plasma-derived HBsA1. At I month. 2 7 ~ of the vaccinecs
were positive for anti-HBs. By 2 months, 68~939' of the vaccinees tlad anti-
HBs, and at 3 months 86%-1009' were antibody positive (Table 23.2). The third
dose of vaccine at 6 months has been pven to 15 persons in o ne of the studies.
resullin1 in a more than 25-fold increase in seometric mean titer.
REFERENCES
1. Valenzuela P, Medina A, Jluner WJ, tt al. Synmesis and assembly ol'bepatilis B virus
surface antipn particles in yeast. Nature 1912; 291:347-350.
2. M~Alur WJ, Buynu EB, Maiacner RZ.. et al. Human hepatitis B vaccine from
recombinant yaat. Nawre 1914; 307:171-IIO.
STUDY 798
00251
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,

Study 798
PURPOSE: To evaluate antibody and clinical responses to 5 mcg,

10 mcg, and 20 mcg doses of the vaccine among healthy
adult paramedics who are negative for hepatitis 8
virus serologic markers .
VACCINE: Yeast Recombinant Hepatitis 8 Vaccine

PRINCIPAL F. Blaine Hollinger, M.D.

INVESTIGATOR: Professor of Medicine, Virology and Epidemiology
Baylor College of Medicine
Department of Virology and Medicine
Texas Medical Center
Houston, TX 77030
SECONDARY Catherine Troisi, Ph.D.

INVESTIGATORS: Baylor College of Medicine
Houston, TX 77030
Dorothy Heiberg, R.N.
Baylor College of Medicine
Houston, TX 77030
STUDY LOCATION: Baylor College of Medicine

Houston, TX 77030
DATE INITIATED: Ap ri 1 11 , 1984
3091 I/1
1 /3/86 ·
00252
Study 798
STUDY POPULATION: The study population is comprised of 109 male

paramedical personnel in the Houston area who were
initially negative for HBsAg, anti-HBc and anti-HBs,
had a normal ALT level and had not previously received
STUDY PROCEDURE: Participants are entered into the study as members of

triplets, one at each dose level, matched on body
weight {within 9 lbs.).
El ig1ble participants receive an intramuscular
injection of vaccine at 0, 1, and 6 months. The
volume (·dose) of the injections received by an
individual is 1.0 ml (20 mcg HBsAg), 0.5 ml (10 mcg
HBsAg), or 0.25 ml (5 mcg HBsAg).
Vaccine recipients are asked to record their
A blood specimen (approximately 30 ml) is obtained
from each participant approximately four weeks before
vaccination and on the day of vaccination.
Post-vaccination blood samples are obtained at 1, 2,
3, 6, 8, 12, and 24 months. All samples are assayed
for HBsAg, ant 1-HBc, ant i-HBs, and ALT. Samp 1es with
an ant i-HBs titer >25 mlU/ml are tested to detenni ne
the proportions of anti-!_ and anti-sl activity.
Samples may be assayed for yeast antibody as required.

5 mcg Lot #974/C-K446 at 0, 1, and 6 months
1 . . Number Vaccinated:
Injection No.
Dose Level _l_ ___L _l_
5 mcg 36 36 36
10 mcg 37 37 37
20 mcg 36 35 35
30911/2
1/3/86
00253
Study 798
RESULTS (CONT.): 2. Serologic Results:

Serology data are available . at 7/8 months. for
36, 35, and 35 participants who received 5, 10.
and 20 mcg injections of vaccine , respectively.
The seroconvers 1on rates and GMTs at 7/8 months
are presented below.
GMT {IIIU/m 1)
Dose -- \ with Ant i-HBs - All - - Responders -
Levels S/N:::_2.1 IIIU/ml :::_ 10 vacclnees SIN :::. 2. \ mlU/11\ :::. 10
5 IIICg 97(35/36) 83(30/36) 72.9 82.2 136 .9

10 IIIC9 97(34/35) 97(35/36) 513 . 1 620.6 620.6
20 mcg 100(35/35) 91 (32/35) 733.0 733 .0 1193.3
Refer to Table l for anti-HBs responses and GMTs

at 12 months and for other time intervals.
Two subjects were found to be anti-HBs positive on
the day of the first injection of vaccine (10 mcg
dose). One of these vaccinees had a 3-fold rise
in anti-HBs at one month and a >4-fold rise at two
months. The other participant developed a >4-fold
rise in anti-HBs titer five months after the
second injection of vaccine.
Clinical follow-up data after each injection are
available for 33, 33, and 32 participants who
received 5, 10, and 20 mcg injections of vaccine.
complaints follow.
30911/3
1 /3/86
00254
Study 798
RESULTS (CONT.):
Type of Dose Freguency in% by Inject;on No.
Complaint Level l 2 3
Injection 5 mcg 14(5/35) 3(1/33) 9(3/34)
Site 10 mcg 11(4/37) 18(6/33) 19( 7/36)
20 mcg 25(9/36) 28(9/32) 21(7/34)
Systemic 5 mcg 34(12/35) 15(5/33) 18(6/34)
10 mcg 30(11/37) 15(5/33) 28(10/36)
20 mcg 33(12/36) 28(9/32) 21 ( 7/34)
Refer to Tables 2 through 4 for listings of

specific clinical complaints by dose level and
injection number. Maximum temperature data are
presented in Tables 5 through 7.
Reactions reported to the OoBRR

A 32-year old male subject had an elevated ALT level
at the t;me of his third injection of vaccine. Two
weeks after the th;rd inject;on of vaccine, the
subject was symptomatic for anorexia and vomiting. He
was icteric, had dark urine ·and elevated bilirubin and
ALT levels. He was negative for anti-HAY, HBsAg, and
anti-HBc. He was diagnosed as having non A non B
hepatitis. This illness was not considered related to
the vaccine.
PUBLICATIONS: Hollinger FB, Sanchez Y, Troisi C, Dreesman GR,

Melnick JL. Inmunogenicity and reactogenicity of
new hepatitis B vaccines. Hepatology 1984; 4:1027
(Abstract).
Hollinger FB, Troisi CL, Pepe PE. Anti-HBs responses
to vaccination with a human hepatitis B vaccine
made by recombinant DNA technology in yeast. J
Infect Dis 1986; 1:156-9.
30911/4
1/3/86
Tab1e I
Antibody Responses Mong He.lthy Mills Following V•ccination "ith

s. 10.or201111::g Injections of Yust Recamlnant Hepititls a V•cclne
lot 1914/C-K446 at O. I, ..id 6 ftonths In Study 1798
~g 10 -=1 20 acg
I 11Hh Antl-ffls GIii i!!lUl•l 2 I "' th Anti -Mts Gfll l•llJ/al} '"Ith Antl~s GIii l•lU/•12
,,_ ■Ill/al All
Resoo11ders
alUl•J
Resoonders
■JU/al 1t1U/■I
Resoonders
alU/111
(llos . ) S/~2.1 ~ 10
aIU/aJ
V.-cc\nees S/~2.1 ~ 10 5/~2.I ~ 10 ""
V•cclnees S/~2.1 ~ 10 S/~2.1 ~ 10 ""
vaccinees S/~2.1 ~ 10
II 6 0.1 6.4 21.0 29 8.6 2.2 6.1 34.0 29 II 1.5 8.1 12.9
(4/36) (2/36) ( 10/35) (3/35) (10135) (4/35)
2 22 14 1.6 18.3 60. 1 14 '40 8.1 14.2 63.3 83 34 10. f 14.8 94.6
(8/36) (5/36) (26/35) ( 14135) (29/35) ( 12135)
3 44 11 1.9 5.8 26.0 86 31 10.1 11.9 61.6 89 SJ 14.3 16.4 38.1

(16/]6) (6/]6) (30/35) (13135) (31/35) (20/35)
6 61 28 2.9 J .S 21.2 94 63 16.0 18. I 38.3 91 19 30.0 .0. 3 SJ.6

(22/]6) ( 10/36) (33/35) (22135) (31/34) (21/34)
J/8 91 18 S1.O 51.9 113.6 91 91 381.0 415.8 415.8 100 89 539.0 539.0 1021.S
(35/]6) (28136) (34/35) (34135) (35/35) (31/35)
12 83 41 12.1 11.6 55. 1 91 8& 14.S 90.4 130.1 91 86 184 ,6 . 211 .4 310.9
(30/]6) ( 11/36) (34/35) (30/35) (34/35) (30/35)
0
0
"'
tJt
VI
30991/2
1/3/96
Table 2
RECONBIHAHT HEPATITIS B VACCitlE
STUDY 0798
TREATttENT
LOT IUl8ER CK446
DOSE 5 ttCG
PATIENT CUSS HEALTH CARE PEASO!flEl
• TOTAL VACCIIIEES I 36 PATIENTSI - DOSE l I

•----------------------------------------------------------------------------1
• DAYS POST VACCitlATIOH I NUl1BER
CLINICAL
CONPUIHTS
1--------------------------------------······------------------------····--··1
I D I 1 I t • 3 I ft I 5 I
WITH
IC011PLAIHTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••I•••••••••••••••••••••
RUCTIOH, LOCAL UNJECT. SITE)
II o\ •
I l
II D •
• D
•• D I• D
II •• S
I I 11,47.1 I I t.9ZI I I O.DZI • I D.07.1 • I D.07.1 I I D.07.1 I I I 14.JZI
-----------------------------------•----------l----------l----------•----------1----------1----------1----------I-----------
PAIH • 1 • l I O • 0 I O I O I I 2
I I 2.97.1 • I 2.91.J I I O.OZI I I 0,07.1 I I O.OZI I I O.OY.I I I I 5.7ZI
I • I • I I I I
SORENESS • 2 I D • D • 0 I o I O I • 2
I C 5.77.1 I I 0.07.I I I O.OZI • I 0.07.1 I I O. OY.I I I 0.07.1 I • I S.7%1
I I I I • • I •
HUH8HESS I 1 I • I O I o I o I o I I 1
I I 2.9%) • I 0.07.1 I I 0.07.1 I I a.oz, I I O.DY.I I I 0.07.) I I I t.97.1
-----------------------------------1----------•----------l----------l----------l----------l----------l----------l-----------
sysnttit I 8 I l I J I O I O I O I I 12
I C 22.97.J • I 2.97.) I I 6.61.1 I I 0.07.) I I D.OY.I I I 0.07.I I I ( 34.3%1
WHOLE BOUY/GENERAL 8 0 0 D 0 0 II
( 22.9'1.J ( D.07.1 C 0.07.1 I O.OZI ( O.OY.I ( D.OZI I 22.91.1
FLUSH 1 0 D 0 0 0 1
( t.9i0 ( 0.07.1 ( o.o:o I 0.07.1 ( o.oio ( 0.0?. I t.97.1
FATJGUE/W£Al<NESS 2 D 0 0 0 D 2
( 5 . T/.1 ( 0.07.1 ( O. DY.I I 0.07.1 ( D.O?.I C 0.0?. I 5. 7Y.I
HEADACHE 5 0 0 0 0 0 5
I 1ft. 3?. I ( o.o;o ( 0.0?.I I o.o;o I D.D?.I I 0.0?.I lft.liO
IHTE&ltlENTART SYSTEM l 0 0 0 0 0 l
I 2.97.1 ( 0.0?.J ( O.OY. I I 0,07.1 ( 0.07.1 I 0.0?. I t.9%1
ttACULAR RASH
I
l
2. 97.1 C
0
O.OZI C
0
0.0% I I
0
o.o;o (
0
0.07.) I
•
0.07.1 (
1
t. ,x1 0
0
DIGESTIVE SYSTEtl 1
2,97.1 (
1
2.9Y.I (
J
8.6%1 I
0
O.OY.I I
0
0.0%) I
•
0.07.l
5
I 14.JY.I
IV
"'
0-
Table 2 (cont)
AECot18IIIANT HEPATil IS B VACCitlE
STUOY 079&
TREATMENT
LOT NUIIBEA CK446
DOSE 5 MCG
PAUENT CUSS HEALTH CARE PERS(NIEL
I TOTAL VACCINEES f 36 PATIEHTSI - DOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST YACCIHATIOU I tfJt1BEA
CLINICAL
CotlPLAltfTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I 3 I 4 I 5 I WITH
ICOHPLAINTS
••••••••••••••••••••••••••••••••••• ••••••••••••••••••••• ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
ASDOttltlAL PAJHS/CRAHPS 0 I
o.o;o I c o.o;o
0
(
t
s. 77.1 (
0
0 .0Y. I ( •
0.0Y. I f
0
0 . 0)0 f
2
5. T/.1
I
DUIIIIHU 0 I 1 2 0 0 0 J
o.o,o I c 2. 9%1 ( 5. 7Y.I f o.o;o ( o. 0Y. I ( o.o:o I 8,6%1
I
NAUSEA l I 0 0 0 0 0 1
2.9;0 I c 0.0)0 ( O.0Y.I I 0.0)0 I 0.0Y.I ( O.0Y.I ( 2 . 9iO
I
HERVOU5 SYST(H 1 I 0 0 0 0 0 1
2.9lO I• 0.0Y. I I O.0Y.I ( 0.0Y.I ( 0.0Y.I ( 0.07.1 I 2.9Y.I
YEATIGO/DIZZINESS I l I 0 I 0 I o I 0 I O I I 1
2.9Y.I o.o;o I I O.0Y.I I I 0.0Y.I I ( O.0Y.I I I O.OY.I I
I f I I 2.9iO
I I I I I I I
ORGANS OF SPECIAL SENSE I l I 0 I 0 I 0 I O I O I I l
2.97.1 I I a.o;o I f O.0Y.I I ( 0.07.I I I o.o;o I ( O.OY.I I I I 2.9%)
I I I I I I I
En PAIN I 1 I o I o I o I a I o I I 1
I f 2. 97.1 I f a. 07.1 I c o. 07. I I f o. 07.1 I ( o. 07.1 I I O. 07.1 I I I 2. 97.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSotlS NITtl COt1PUINTS I 11 I 2 I 3 I O I O I O I I 16
I c 31.47.1 I c s. 77.1 I c 8.67.1 I c o.o;o I c o.o;o I • o.ox, I I I tt5. 77.1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
PEIISOIIS WITH tlO COffl'UIHTS I 24 I JJ I 32 I JS I O I O I I 19
I I 611.6)0 I I 9lt.37.) I C 91.4Y.I I (100.07.I I I 0.07.1 I f O.0Y.I I I I 54.:SY.I
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
PEAsot1s WITH HO DA TA I 1 I 1 I 1 I 1 I o I o I I 1
I I 2.117.J I I 2.117.1 I I 2.8:o I I 2 . 117.1 I I O.0lO I I O.0ll I I I t.8i0
0
0
l'\J
111
.....
Table 2 (cont)
PATIENT COUNT CLIHICAL COHPLAIHTS
RECOl18IHAHT HEPATITIS B VACCillE
STUDY I 0798
TREATtlEHT
LOT NUlll!ER CK446
DOSE I 5 11CG
PATIEITT cuss·: HEALTH CARE PERSOMfEL
I TOTAL VACCINEES C 16 PATJEHTSI - DOSE 2 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATIOH . I tU1BER
CLIHICAL
COttPUIHTS
1----------------------------------------------------------------------------•
I O I 1 • 2 I l • ., • S •
MITH
•cOHPUIHTS
••••••••••••••••••••••1t11••••••••••••••••••••••l••••••••••••••••••••••••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
REACTION, LOCAL UHJECT. SITEJ II 1 II O I• O I• O
•• 0
•• 0
•• •• 1
I f 3.07.1 I I 0,07.) I I 0.07.1 I C 0.07.1 • f 0.07.1 • I G.07.1 I I f ].07.)
-----------------------------------1----------l----------l----------l----------l----------l----------1----------l-----------
sOPmEss I 1 I o I o I a • o • a I I 1
I , 1.ox1 I c o.or., I , o.ox, I 1 0.01.1 I I a.ox, I c 1.ox1 I I l 1.ox1
---------. -------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
srsnH1c I 5 I tt I 2 I 1 I a I o I I 5
• C 15.27.1 I I 12.17.J I c 6,17.1 I C l.OXI I C 0.07.1 I C t.07.1 I I l 15.27.1
WHOLE BOOY/GEHERAL I 2 2 2 1 0 a It
6.17.1 I 6 . 17.) I 6.1:0 I ].07.1 I 0.07.1 I t.07.1 I 12.17.J
HAUISE 0 0 1 0 0 0 1
• 0.07.1 I 0.07.1 I J.OiO I O.Ol!I I 0.07.1 I e .07.1 I J.07.1
HEADACHE I 2
6.llO I
2
6,llO
1
C J.07.1 I
1
1.0;0 C
0
,.o:o ( •
,.or., C
3
9.17.1
RESPIRATORY I l
3 . 07.1 I
1
3.07.I I
0
I.DY.I C
0
o.o:o C
0
o.o:o C
•
I.DY.I
l
C 3.07.1
PHARYNGITIS ISORE THROATI I l
1.0:0 I
1
3 . 07.) I
0
0.07.1 I
0
0.07.1 C
0
0.07.1 I •
0.07.1 I
1
3.07.1
UPPER RESPIRATORY IHFECT., NOS I 1

l.OiO I
a
0.07.1 I
0
0.07.1 ( •
,.ox, I
0
o.o:o (
0
1.17.1 (
1
1.0:0
taJSCUlOSftELETAL I 2
6 .JX I I
1
1 . 0:0 I
0
o.o:o (
0
0.07.I I •
O.OiO I
a
o.o:o I
2
6.J7.I
t11'ALGIA J l a 0 0 a J
• 3.07.1 I 3.07.1 ( 0.07.1 I 0.07.1 I O.OY.I ( O.OY.I I 3.07.1 0
0
NECK PAIN I 1 0 a 0 ·o
0.07.)
0
o.o;o
1
1.0;0
IV
\11
3.07.I C O.OY.J C t.07.1 I O.OlO I I C (JI
Table 2 (cont)
PATil:NT COUNT CLINICAL COHPLAINTS
RECot18Jl~HT HEPATITIS B VACCJIIE
STUDY I 0798
lREATt1EHT
LOT I-IJtlBER Cl<4'46
DOSE S t1CG
• TOTAL VACCIHEES C 16 PATIENTS I - DOSE 2 •

l----------------------------------------------------------------------------1
• OAYS POST VACCINATION • HlMER
CLINICAL •---------------------------·---------·····----•·-----·------------------·---• MITH
COMPLAINTS • 0 I 1 I 2 • l I 4 I 5 • •c0t1PLAJHTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••I••••••••••••••••••••••••••••••••
OffG,.HS OF SPECIAL SENSE II 1 II l I• O I• O
•I O
II O I• I• 1
I I J.01.1 I I J.01.1 I I 0.07.) I C 0.07.) I I 0.07.) • I D.01.) I I I 3.01/.)
EARACHE II · 1 II 1
I
I O
•
I O
I
I O
•
I O
I
I I
I 1
I I J.01.I I I J.07.1 I I 0.07.) I I 0.07.) I I 0.07.1 I C 0.07.1 I I I J.01/.I
-----------------------------------1----------l----------l----------l----------l---·-·-·-·1----------I----------I-----------
PERSONS WITH Cot1PUINT9 I 6 I lt I 2 I l I O I O I I 6
I I 18.21.1 I I 12.17.1 I I 6.17.1 I C J.07.) I I 0.07.1 I I 0.01.1 I I C 18.21.)
-----------------------------------1----------l----------l----------l----------t----------l----------l----------l-----------
PERsONs WITH NO CotlPUIHTS I 27 I 29 I J1 I 32 • 1 I O I I 27
I I Bl.BY.I I I 87.91.1 I I 9J.97.I I I 97.07.) I (100.07.1 I I 0.01.1 I I I 91.81/.1
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
PERSOts WITH HO DATA • l I J I J I J I O I O • I J
• C a.JY.I • I 8.J;'.I • C 8.37.1 I I 8.J;o • I o.o;o • I 0.0;'.I • • I 8.37.1
0
0
N
I.II
-.0
Table 2 (cont)
PATIENT COU,IT CLINICAL COHPLAINTS
RECOIIBINAHT HEPATITIS 8 VACCUIE
STUDY 9798
TREATHENT
LOT NUll8ER Ck44ft
DOSE 5 t1CG
PATIEtlT CUSS HEALTH CARE PERSONNEL
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINE ES C 36 PATIENTS I - DOSE 3 I
1----------------------------------------------------------------------------I
I DAYS POST VlCCIUlTIDN I 1-UiBER
CLINICAL
C0NPLAINTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I J I 4 I 5 I
WITH
ICOHPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
RUCTION, LOCAL UNJECT, SITEI I 2 I 1 I o I 0 I o I 0 I I 3
I C 5 . 9%1 I C 2.9%1 I I 0.0%1 I I 0.0%1 I I 0.07.1 I ( a.ax, I I I 8.8%1
-----------------------------------1----------I----------
PAIN ON IIIJECTION I 1 I O
----------
O
----------
O
----------
O
----------1----------1-----------
o I I l
I I 2 , 9%1 I C 0.0%1 I 0.0Y.I I O.0Y.I I 0.0Y.I ( 0.0Y.I I I I 2 . 9%1
I I
PAIN I 1 I o o o a o I I 1
I c 2.,x1 I c o.o;o c o.ox1 c o.ox1 c 11.0;.1 c o.ox1 I I c 2.9?.1
.I I I I
SORENESS I 0 I 1 o o O O I I l
I I II. 0% I I I 2 . 9% I I O. 0% I I O. 0% I I O. o:o I 0. 0Y. I I I I 2. 9lO
I I I I
PARESTHESlA I l I O a 0 0 O I I 1
I I 2.9%1 11 0.0;.1 · I 0.0%1 I 0.07.1 I o.o:o I e.o:o I 11 Z.9Y.I
-----------------------------------l----------l----------l----------l----------l--·-------1----------l----------l-----------
sYsTE11Ic I 3 I J I J I O I O I O I I 6
I I 8.8%1 I C 8.8%1 I I 11.IIY.I I I 0 , 0%1 I I 0.07.1 I I 0.0lO I I I 17.6%1
----------------------------------- ----------------------------------------------------------------------------------------
I
WHOLE BODY/GENERAL ] 1 l I 0 0 0 4
I 8.8%1 I 2.97.1 I 2. 97.1 I I O.0iO I II .07. I ( 11 . 0%1 I 11.lliO
I
FEVER ITENP. HOT REPORTEOI 0 0 l I 0 0 0 l
I 0.0iO ( o.o:o I 2.9%1 I I 0.07.1 I 11.07.1 ( o.o;o I Z.97.1
I
FATIGUE/WEAKNESS 2 l 0 I 0 0 0 2
I 5.9%1 I 2.91.1
• II .DY. I I I 0.0)(1 I 0. 0Y. I I 0.0%1 I s. 97.1
I
HEADACHE l 0 0 I 0 0 0 1
I 2.9%1 ( 0.0%1 I a. DY. I I
I
I 0.0%1 ( 0.0%1
• 0.0Y. I I t. 97.1
RESPIRATORY
•
G.0%1 I
1
Z .9)(1 I
1 I
2.9)(1 I I
0
0.0)(1 I
0
a.ox, (
0
0.0)(1 I
l
2. 9Y.I 0
0
I IV
RHINITIS I 0 l l I 0 0 0 1 O"
0 . 0%1 I 2. 97.1 I z. 9)( I I I O. 0Y.I I 0.0Y.I I o.o;o I 2. 9Y.I C)
Table 2 (cont)
PATIENT COUNT ClINtCll Cot1PlAIHTS
IIECOHBINAtlT HEPATITIS 8 VACCINE
STUDY 0798
TRUTNENT
LOT NUt1BEII CK446
DOSE 5 tlCG
PATIEHT CUSS HEALTH CARE PERSONNEL
I TOTAL VACCINEE9 I 36 PATIENTS I - DOSE J I

Il----------------------------------------------------------------------------1
DAYS POST VACCINATION I t1Ut18ER
CLINICAL l----------------------------------------------------------------------------1 WITH
Cot1PlAIHT9 I O I 1 I 2 I J I It I 5 I ICOt1PUINT9
••••••••••••••••••••••••••••••••••• ········••1••······••1••·······•1••··················•1••······••1••······••1••········
I I I I I I I
DIGESTIVE SYSTEH 0 I 1 I 0 I 0 I 0 I 0 I I l
0.0iO I I 2,9;0 I 1 0.01.1 I 1 0.07.1 I I 0.07.1 I1 0.07.1 I I I 2, 97.I
I I I I I I I
OTHER 0 I 1 I 0 I 0 I 0 I 0 I I 1
0.OlO I I 2,9;0 I 1 0.01.1 I 1 0.07.1 I 1 0.07.t I1 O.OlO I I I 2,97.)
I I I I I I
UROGENITAL 9lSTEH 0 I 0 I 1 I 0 I 0 I 0 I I l
o.o:o I 1 0.0iO I I 2,9;:1 I I 0.01.1 I 1 0.01.1 I 1 0.01.1 I I I t.97.)
OTHER I DI DI 11 DI OI OI I 1
I l 0.01.1 I l 0.01.1 I l 2.97.1 I l 0 . 01.t I I 0.07.1 I l o.07.1 I I I 2.97.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERS~ WITH CottPLAlHTS I 4 I o\ I J I o I o I O I I 8
I l 11.87.1 I 1 11.ex1 I l 8,87.t I I o.ox1 I l 0,07.1 I I o.ox1 I I 1 2J . s1.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEASOHS WITH NO CottPUINTS I JO I JO I JI I 34 I o I o I I 26
I I 88.27.) I I 88.2)0 I l 91.27.1 I ll00.07.) I l 0,07.) I l O. 0lO I I I 76.SiO
-----------------------------------1----------1----------I----------I----------I----------I----------I----------I-----------
PEASOHS WITH NO DATA I l I l I 1 I l I O I o I I l
I I 2. 97. I I f 2. 97.1 I I 2 • 97. I I I 2. 97. I I I 0. 07. I I I O. 07. I I I I 2 . 97. I
0
0
n,
-
0-
Table 3
PATIENT C~T CLINICAL C0t1PLAIHTS
RECOIIBINAtfT HEPATITIS 8 VACCINE
STUOY 0798
TREATMENT
LOT IIIJIIBER CK446
DOSE 10 MCG
PATIENT CLASS HEALTH CARE PERSOHHEL
I TOTAL YACCINEES l 37 PATIENTS I - DOSE l I

1----------------------------------------------------------------------------I
I OATS POST VACCIIIATION I NUtlBER
l----------------------------------------------------------------------------1
CLINICAL
COIIPLAIHTS
................................... I
, O
..........
I
I l
,
..........
I
I 2
.......... ,
I
I
3
.......... I
,
I
4
.......... I 5
,
..........
I
I
, WITH
.......... ICOMPUIITTS
..........
I
,
I
,
I
REACTION, LOCAL UHJECT. SITU I J I O I 2 I l I O I O I I 4
I l 8,1%1 I C 0.07.1 I l 5.4%1 I l 2.7½1 I C 0.0½1 I ( O.Oll I I I 10.8½1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sORENESS I 2 I o I 2 I 1 I o I o I I 4
I 1 5 . 4%1 I I o.or.1 I 1 5.47.1 I 1 2.1r.1 I I o.or.1 I , o.or.1 I I , 10.8r.1
I I I I I I I I
PRURITIS I ITCHING I I l I O I O I 0 I 0 I t I I 1
I I 2.7½1 I I 0.0½1 I ( 0.0½1 I l 0.0½1 I ( o.or.1 I I 0.0½1 I I ( 2.7½1
I I I I I I I I
PARESTHESIA I 1 I O I o I o I o I o I I l
I , 2. 77. 1 I c o. o;o I , o. ox I I c o. or. 1 I c o. o:o I , o. or. 1 I I c 2. n 1
-----------------------------------1I ·---------1----------1----------1----------l----------l
svsTEMIC 7 I 5 I J I l I O I
----------l----------l-----------
D I I 11
I l 18.97.1 I I lJ.57.1 I I 8.17.1 I C 2.77.1 I l 0.0½1 I l O,OXI I I l 29.77.1
latOLE BODT/GEIIERAL 5 4 J 1 0 0 I 8
l 13.5½ I I 10.8½1 I 8.liO ( 2.7½1 ( o.o;o ( o.o:o I I 21.6½1
I
FATIGUE/WEAKNESS 3 4 2 l 0 0 I 6
( 11.lY.1 l 10.8½1 C 5.ft%1 I 2. 77.J I o.o;o I o.o;o I 16,2½1
tlAUISE
I
1
2.7%1 I
1
2.7i0 I
0
O.OiO ( •
0.0%1 I
0
0.0½1 I
0
0.0%1 I
1
2. 77.1
HUOACHE 2 0 1 0 0 o 3
I 5.47.1 I 8.07.1 ( Z.7½1 I 0.0½1 ( o.o:o ( 0.0%1 I 8.li()
INTEGIJtlEHTART SYSTEM 1 0 0 0 0 o 1
( 2. 77.1 I 0.0½1 I 0.0XI ( o.or.1 I 0.0%1 I t .ox1 I 2.7%1
RASH, NOS
(
l
2. 7½1 (
0
t.OY.I (
0
0.0½1 (
•
0.0½1 I
o
0.0½1 I
0
0.0%1 (
1
z.no 0
0
IV
RESPIRATORY I l
2.7½1 (
0
o.o:o I
0
O.DXI C
0
o.o:o (
o
0.0½1 I •
0.0½1 (
1
2, 7½1
0-
1\1
Table 3 (cont)
PATIENT COUil CLINICAL COl1PLAINTS
RECot1BIHANf HEPATITIS B \IACCIIIE
STUDY 0798
TREATt1ENT
LOT IIUHBU CK446
DOSE 10 tCG
PATIENT CLASS: HEALTH CARE PERSONfEL

Il----------------------------------------------------------------------------1
OATS POST VACCIIIATION I NUt18ER
CLINICAL
COl1PUIHTS
1----------------------------------------------------------------------------I
ICOMPLAINTS
·······~··························· ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
UPPER AESPIAATORT INFECT., NOS l 0 0 0 0 0 l
t. 7XI I 0.0:r.1 ( O.OY.I ( O.OY.I I 0.0:r.1 I 11.0Y.I ( 2.7i!I
ttUStULOSKElETAL l 0 D 0 0 0 1
I 2.7:iO I 0.01.1 ( II.DY.I ( O.OY.I ( 0.0:r.1 I O.OY.I ( 2.7il.l
NYAlCIA l 0 D 0 0 0 1
2.7l0 ( 0.0:r.1 ( 0. DY.I ( O.OY.I ( O.OY.I ( 0.0:r.1 ( t. 17.1
PSTCHIATAIC/BEHAVIORAL
•
O.OY.I (
1
2. 71.) (
D
0. DY.) (
0
O. OY. I (
0
o.o:r., (
0
O.OY.I (
1
2.7¼)
I
JHSot1Nll/OJSTURBED SLEEP I D I 1 I D I O I O I O I I 1
I c o. OY. 1 I c t. 11. , I c o. OY. t I c o. OY. 1 I I o. 0:1.1 I I o. o:r. 1 I I 1 2. n 1
----------- ·-----------------------1----------1--
PERSONS WITH tOt1PlAJNTS I 10 I
--------l----------l----------1----------1----------1----------I-----------
5 I 5 I 2 I O I O I I 14
I I 27.0XI I I 13 . 5¼) I I U.51.1 I C S.41.t I c 0.0;:1 I c 0.01.1 I I I 37.8il.l
-----------------------------------1----------l----------l----------l----------l----------l----------1----------I-----------
PEASOHS WITH NO COMPUJHTS I 27 I 32 I 3Z I 35 I O I O I I n
I c n.oY.1 I , 86.s;o I , 86.s:r.1 I c 94.67.I I c o.o;o I , ,.ox, I I c 62.2:r.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEASONS WITH NO DA TA I O I O I O I O I O I O I I o
I I O. 01. I I f O. OX I I C O. 01. I I C O. OX I I I O. O¼ I I C I. OX I I I C O. Oil. I
0
0
!\J
0-
......
Table 3 (co1it)
PATIENT CCXJfT CLINICAL CottPLAINTS

RECOHBIHAHT HEPATITIS 8 VACCINE
STUOl 079&
TRU111EHT
LOT IUIBER CK446
OOSE lD 11CG
• TOTAL YACC lHEES I 37 PA TIEHTS I - DOSE 2 •

•----------------------------------------------------------------------------•
• DAYS POST VACClHAllOH • HJl1BER
CLINICAL
COMPUIHlS •-----------------------------------------------------------------
I O I 1 I 2 I 3 I 4 I 5
-----------•
I MITH
ICOMPUlHTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
• • I I I I I •
REACTION, LOCAL UHJECT. SITE:I I 4 • 0 I 1 . I O I 1 I O I • 6
I c 12 . 1:0 I c o.o;o I c :s.o:o I c o.o;o I uoo.0,:1 I c 0.0,:1 I • t 1e.2;O
-----------------------------------l----------l----------l----------l----------l----------l----------l----------•-----------
s011Et1Ess I 3 • 0 I l I O I O I D I I 4
I I 9.llO • t 0.0l'!I I C 3.0ZI I t 0.Dl'!I I C D.0l'!I I C 0.0l'!I I I I 12.11.1
I I I I I I I I
TEl-l>ERtlESS • 1 I O I o I D I 1 I o I • 2
• t 3.01.1 I I 0.0l'!I I C 0.07.) I I o.0l'!I I 1100.0l'!I I C O.Dl'!I I • I 6.17.1
I • I I I I I I
PRUUTIS I ITCHING I I 1 I a I O I O I O I o I • 1
I C 3.01.I I c 0.01.1 I I o.ox, I c 0.01.1 I c 0.0,O I t 0.01.1 I • I 3.0iO
-----------------------------------l----------l----------l----------l----------l----------l----------l----------•-----------
sysn111c • 2 I 3 I 2 • 3 • o I o I • s
I t 6.li!I I c 9.11.1 I I 6.11.1 I t 9.11.1 I I 0.01.1 I I 0.01.1 I • I 15.2iO
WHOLE BODY/GENERAL 1 I I I I
• 3.01.1 I• I
3
, • 11.1
2
I 1 6.11.1 I 1
3
9.11.1 I t
0
•
0.01.1 • C
0
0.01.1 I• • t 12.1;0"
I I I I I
FATIGUE/WEAKNESS I • I• t I I I
0
o.o:o • ( • 3
9.11.1 I I 6.17.1 •I 1 3
9.11.1 I I
0
0.07.1 • I
0
o.o;o I• I I 12.liO"
I I I
HEADACHE 1 • 0 I 0 • 0 I 0 • 0 •
I I l
•• I 3.0)0 • I • 0.0,:1 • ( 0,01!1 •• I o.o,:, • ( •
0.01!) • C o.o,:, • I < 3,0iO
I I I I I I I
DIGESTIVE SYSTEl1 I l I 1 I 0 I 0 0 I• 0 I I t
C 3.07.1 • ( 1.0:0 I c 0.07.) • I 0.0)(1 • I • o.ox, I C 0.07.1 • I < 6.li!I
DIARRHEA D l 0 0 . 0 0 1
C O. 07.1 J.0lO 0.07.1 o.o;o • o.o:o I 0.07.1 3.07.1
I
NAUSEA
C
1•
3.01.1 • I
o•
0.01.I I I
,.
0.07.1 I C
o•
o.ox, • I
o•I
0.07.1 I
DI
o.o:o I
I
I I
1
3.0lO
0
-----------------------------------•----------•----------l----------•----------t----------t----------1----------1-----------
PEASOHS MITH COHPUINTS I 6 • J • 3 • 3 I l I Cl I I 11
~
N
I I l& . 27.1 • ( 9.11.1 I C 9.17.1 I C 9.liO I 1100.0l!I I I 0.07.1 I • I 33.]iO 0-
c
Table 3 (cont)
PATIENT COUHT ClIHICAL Cot1PLAINTS
RECotl8IHAHT HEPATITIS B VACCINE
STUO'f 0798
TREATt1EHT
LOT .UIBER CK446
DOSE lD t1CG
PATIENT CLASS HEALTH CARE PER~EL
I . TOTAL VACCitlEES 1 l7 PATIENTS I - DOSE IZ I

l----------------------------------------------------------------------------1
I OATS POST VACCINATION I ~ER
CLINICAL
C0!1PLAINTS
l----------------------------------------------------------------------------1
I O I l I IZ I J I 4 I 5 I
WITH
ICortPUJHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
PERS0t1s MITH NO COHPLAIHTS I 27 I lO I JO I 30 I O I O I I 22
I I 81. 8)0 I 1 90 • 9Y. I I 1 90. 9Y. I I 1 90. 9Y. I I 1 0. OY. I I I O. O?. I I I I 66 • 7Y. I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEIISOHs WITH NO DATA I 4 I 4 I 4 I 4 I O I O I I 4.
I l 10 . 8?.I I t 10.87.1 I t l0.8ZI I 1 10.8¼1 I t 0.0:i:1 I I o.oio I I t 10.e:1.1
0
c::>
N
O"
\Jt
Table 3 (cont)
PATIENT COlMT CLINICAL COttPLAINTS
RECOtfBIHANT HEPATITIS 8 VACCJl◄ E
STUDY 0798
TI!EATrtENT
LOT HlltlBER CK446
DOSE 10 ttCG
PUUHT CLASS HEALTH CARE PEASottlEL
I TOTAL VACCIIIEES I 37 PATIENTS I - OOSE l I

1-------------------------------------------------------------------------
I DAWS POST VACCINATION
__ I, t-AJHBER
CLINICAL
COIIPUINTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I l I 4 I S I
MITH
I COMPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••••••••••••••••••••••••l••••••••••I•••••••••••••••••••••
I • I I I I I I
RUCTION, LOCAL IIHJECT, SITEJ I S I 3 I l • 0 I O I O I I 7
I I 13.97.J I I 8.lZJ I I 2.9ZJ I I o.oZJ I f O.OZJ I I O.OZJ I I f 19.47.1
-----------------------------------,---------- ---------- ---------- ---------- ---------- ---------- ---------- -----------
PAIH OH INJECTION I l
2.8ZI (
0
•
o.o;o
0
(
0
0.07.1
0
I Q.OZI
l
I O.OZI ( 0.0)0 I 2.8)0
PAIN I
I I
l
2.8?.J ( •
o.o;o f
a
O. DY.I I
0
0.07.1 I
a
O.OY.I I
0
0.07.1 I
1
2.87.1
I
SORENESS I 2 3 1 0 0 0 4
5.67.J ( 8,liO f 2. 9Y. I I o.o;o I O.OY.I f 0.0?. I I 11,lY.I
1 1· a 0 0 0 2
lEtlOU!NlSS
• 2.8:0 ( 2.e:o ( 0.0?.I I o.o:o ( o.o;o I 0. 0Y. I f S.6XI
I
PARESTHESIA I 1 I O I O I O I O • O I I l
I I 2.8Y.I I I 0.07.1 I I t.07.1 I I o.oz1 I I 0.07.1 • f 0.0?.I I I f 2.8:!I
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
svsn:rtic I 6 I s I l I 2 I o I o I I 10
I I 16.T/.I I I ll.97.J I I 8.67.I I I 5.77.1 I I 0 . 07.1 I I 0.07.1 I I I t7.87.I
----------------------------------------------------------------------------------------------------------------------------
I
WHOLE BOOY/GEHERAL I 5 1 1 I 0 0 I 0 6
ll.9i0 ( 2 .87.1 I 2.9i0 I I 0.0?.I I 0.0?.J • I 0.0?.I I U.71.1
I I
fATI6UE/W£A~HESS I 0 0 1 I 0 0 I 0 l
O.OiO I 0.01.J I 2. 91. I I I 0.0?.J I o.o:o I I o.o:o f Z,8?.J
I I
NEAOACHE I 3 l 0 I 0 0 I 0 3
8.37.J ( !.8i0 I 0.07.1 I 1 0,07.I ( o.o:o I c 0.0)(1 ( 8.3)(1
I I
llGffTHEADEO I l 0 0 I 0 0 I 0 l
2.87.1 ( 0.0?.I I o. O)( I I I 0 . 0?.I ( D.07.1 I I 0.07.1 ( 2.81/.I 0
I I 0
ACHINESS I
(
l
2.87.1 (
0
o.o;o ( •
o.oz1
I
I 1
0
0.07.1 (
0
0.07.J
I
I I
0
0.07.1 I
1
2.87.I
N
"'
0-,
Table 3 (cont)
PATIENT COUNT CLINICAL COl1PLAINTS
AECOHBINANT HEPATITIS B VACClllE
STUDY 0798
TRUTtlEHT
LOT Hl.Jt18ER CK446
DOSE 10 t1CG
PATIEHT CLASS HEAL TH CARE PERSOfltEL
----------------------------------------------------------------------------------------------------------------------------
I TOTAL YACtlHEES I 37 PATIENTS) - DOSE 3 I
1----------------------------------------------------------------------------I
CLINICAL 1--------------------------------------------------------·-------------------I WITH
COMPLAINTS I 0 I 1 I 2 I 3 I 4 I 5 I ICOMPLAINTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
INTE6Ut1EHTART SYSTEtl 0 l 0 0 0 D l
o.o;o t.ax, O.OXJ
t1ACULAA RASH
' 0
' l
' 0
I 0.0?.I
0
' 0.0?.I
0
'
O.OXJ
0
'
2.8?.I
l
I o.o;o t.ax, o.ox, o.ox, o.ox,
PAURITIS/ITCHIHG 0
' l
' 0
I
0
I
0
I 0,0?.J C 2,8XJ
0 1
I O.OXI z.ax, ,.ox, ( 0.0?.I ( o.o;o 0.0?.I 2.8?.I
RESPIRATORY l
C
0
' 0 1 0
C
0
C
t
I 2,8?.I o.ox, I o.ax, I 2.9)0 I O.OXI 0.0)0 5.6XI
RHINITI!I 0
C
0 0 l 0
C
0
' 1
C o.o::o o.ox, O.OXI I 2 , 9)0 ( o.ox, 0.0:1.1 2.8)0
' C (
PHAAYHGITIS CSORE THROAT I l 0

' 0 0 0 0 1
2.8XI O.OXI I t.OXI o.o:o I O.OXI 2.8)!1
' '
( I 0.0?.I (
,-,SCULOSKELETAL 0 l l 1 0 0 2
o.o::o 2 .BY.I 2,91.1 2.9XI O.OXI
' ' I I I C O.OXI
' 5.6XI
ARTIIAALGIA IOTHERI
'
0
O.OXI C
0
o.ox, I
0
O.OY.I
'
1
2,9:'.I . 0
0 .OY.I I
0
O.OXI
'
1
2.8:'.I
BACK PAIN 0 0 l 0 0 0 1
I O.OXI O.OXI I Z.9XI ( O.OXI I O.OY.I 0.0:1.1 I
HECK PAIN 0
' 1 0 0 0
' 0
2.8:'.I
1
o.o:o 2.a;o a.ox, I 0,0)0 o.o;o o.ox,
SHOULOEA PAIN
' 0
' l
' 0 0
I
0
' 0
( 2.8?.I
1
0.0)() 2.8XI O.OXI o.o;o C a.ox, o.ox, t.ax,
' C
C ( (
C
OIGESTIYE STSTEN I l 2 0 0 0 0 3 0
2.8XI ( 5.6XI ( O.OXI ( o.o:o C o.ox, I o.ox, C l.]XI N
0-
NAUSEA I l l 0 0 0 0 2
.....
2.8:0 2.8)0 o.o;o 0.0)0 0.0:1.1 o.o:o I 5.6XI
'
( C C C
Table· 3 (cont)
PATIENT C~T CLINICAL Cot1PLAINTS
AECot18INANT HEPATITIS B VACCINE
STUDY D798
TREATNENT
LOT tUBEI! Cl<446
DOSE 10 t1CG
PATIENT CLASS HEALTH CARE PERS~EL
I TOTAL VACCIHEES C 17 PATIENTS I - DOSE J I

l----------------------------------------------------------------------------1
• DAYS POST VACCINATION • HUl18EA
1----------------------------------------------------------------------------I
CLINICAL
COMPLAINTS •
•
0 •
•
l • 2
•
• l
, I 4
, I 5 I
, ,
WITH
.CDHPUINTS
......................•............•..........•..........•.......... •......... ..........•.......... .......... ..........
I I • I I
01l1EA • 0 I l I O I O I O I O I • 1
I c o.or.1 I 1 2.er.1 I c o.or.1 I c o.or.1 I c o.or.1 I c o.or.1 • • c 2.er.1
I I I I I I I I
PSYCHIATRIC/BEHAVIORAL I O I 1 I 1 I 1 I O I O I I l
I , o.or.1 I c 2.er.1 I c 2,9r.1 I c 2.,r.1 I , o.or.1 I c o.ox1 I I c 2.er.1
I I I I I I I I
IHS<MIIA/OISTUIIBED SLEEP I O I 1 I 1 I 1 I O I O I I l
I I o.or.1 I c 2.e;,.1 • c 2.9r.1 I c 2.,r.1 I , o.or.1 I c o.or.1 I I , 2.er.1
-----------------------------------1----------l----------l----------l----------l----------l----------•----------I-----------
PERSotls MITH cor1PUINTS I , I e I 4 I 2 I o I o I I 12
I I 2s.o:1.1 I I 22.2Y.) • I 11.4%) I I s.nl I I 0.0)() • I o.or., I I I lJ.]iO
-----------------------------------•----------l----------l----------l----------l----------1----------1----------1-----------
PEASONS MITH NO CotlPLAINTS I 27 • 28 • ll • ll I O I o • I 24
• I 75.0lO I I 77.8l0 I I 88 .6%1 • C '>4. J)(I I I 0.0%) I ( 0.0%) I I I 66. 7)()
-----------------------------------1----------I---
PERSOIIS WITH HO DATA I 1 I
.------l----------1----------1----------1----------I----------I-----------
1 I 2 I 2 I O I O I I l
I I 2.r/.1 I I 2.77.J I c S.4XI I c 5.4%1 I I o.or.1 I c o.or.1 I I c 2.7XI
0
0
.N
a-
(JI
Table 4
PATIEIIT COUNT CLINICAL COMPLAINTS
RECotlBINANT HEPATITIS B YACCI14E
STUDY 0798
Tl!UTHENT
LOT IUBER CK446
DOSE 20 ttCG
PATUNT CUSS HEALTH CARE PER!IONNEL
I TOTAL YACCIIIEES I 36 PATIENTS I - OOSE l I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUtfBER
CLINICAL
COtlPUltlTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I J I 4 I 5 I
WITH
IC011PLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
RUCTION, LOCAL <INJECT. SlTEI I 8 I 2 I 1 I 0 I O I O I I 9
I I 22.2ZI I C 5.6ZI I C 2.8XI I I O.OXI I I O.OZJ I I O.OZJ I I I 25.0XJ
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sORENtss I e I 2 I o I o I o I o I I 9
I I 22.2ZI I I 5.6XI I I D.OXI I I O.OZI I I O.OZJ I I O.OZJ I I f 25.0XJ
I I I I I I I I
STIFFNl:SS/TIGHTNt:SS I l I O I O I O I O I O I I 1
I I 2.81.1 I I O.OZI I I O.OXI I I 0.01.1 I I 0.07.J I I O.OXI I I f 2.81.1
I I I I I I I I
ECCHYHOSIS I D I 1 I 1 I O I O I O I I 1
I I D.OX) I I 2.8XI I I t.8)0 I I O. DXI I I O.OXI I I o.or., I I I 2,81.1
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
svsn111c I 5 I 5 I 5 I 4 I O I O I I 12
I I U.97.1 I I l3.9XI I I 13.97.1 I I 11.lXJ I I O.OXI I I O.OXJ I I I JJ.JXI
lffOLE llODY/GENERAl I 4 3 t 2 0 I 0 I I 8
I 11.llO I 8. 37.1 I S.67.l I 5.6)!1 I O.OXI I I O.OXI I I I 22 , 27.J
I I I
FEYER ITEMP. NOT REPORTED! I 1 0 0 D 0 I 0 I I 1
o.o;o o.ox, I I o.o:o I I 2.81.1
'
2.8i0 ( ( O.OZI O.OXI ( I
II '
FATIGUE/WEAKNESS I 2 1 0 0 0 0 3
I 5.61.1 I 2.e;o I o.o:o I ( 8 . 31.)
HEADACHE
I
I
I
1 1 1
O.Ol!I
1
I O.Ol!I
0
O.Ol!I
0
' l
2.8i0 I ( 2.8i0 O.OiO I
ACHINESS I 0
2.ez1
1
2.8ZI
1
I
1
' 0
I D.Ol!I
D
8.3XI
l
I I 0.07.l I 2.8i0 I 2.81.1 I 2.IS?.I I O.OXI ( O.Ol!I I 2.8XI
I
llfTE~ENTART SYSTEH I 1 0 0 1 0 0 2
2.8?.I ( O.OXI ( 0.0)0 I t.8XI I O.OiO I 0.07.1 I 5.67.1 0
0
IV
PRURITIS/ITCHING I D 0 0 1 0 D 1 0-
I D.OXI I o.or.1 I o . o;o I t.8XI I o.o:o I O.DZI ( 2 . 87.I ,0
Table 4 (cont)
RECONOIHAHT HEPATITIS B VACCINE
STUOY 0798
lR[ATHENT
LOT HUIIBER Cl<446
DOSE 20 tlCG
PATIENT CUSS IIUL lH CARI! PERSONNE l
I TOTAL VACCIIIEES I 36 PATIENTS I - DOSE l I

1----------------------------------------------------------------------------I
I DAYS POST VACCltlAlION I NUH8ER
CLINICAL l----------------------------------------------------------------------------1 WITH
..........................•........ ,I ..........
o
,I .......... ,I .......... ,I .......... ,I .......... ,I......•...
s
,I...•......,lcottPUIHTS
COl1PLAINTS 1 2 J 4
......... .
RASH, HOS 1 0 0 0 0 0 1
2.8iO 0.0iO 0.0%1 0.OY.I I 0.0Y.I O.0Y.I 2 . 11:0
RESPIRATORY 0 0 2 l 0 D 2
o.o;o o.o;o 5.61.1 2.8iO I 0.0iO O.0Y.I 5.6)(1
PHARYNGITIS ISORE THROAT) 0 0 l 0 0 0 1

0.0iO 0.0Y.I 2.87.1 0 . 0Y.I I 0.0%1 o.o:o 2.8)(1
UPPER RESPIRATORY INFECT. , HOS 0 0 0 l 0 0 l

0.0iO 0.0%1 0.07.1 2.8Y.I I 0.0%1 0.0iO 2 ,8)(1
COUGH 0 0 l 0 0 0 l
0.0%1 t.0%1 2.8)0 0.D%1 I O.OY.l o.o;o 2.8Y.I
Kr.lCULOSl<EltTAL 0 0 1 l 0 0 1
0.0%1 o.o;o 2.87.1 2.8Y.I I 0.0Y.I 0.0Y.I 2 . 8Y.l
BACK PAIN 0 0 l l 0 0 1
0.0%1 0.0iO 2.8)0 2.87.l I 0.0%1 O.0Y.I 2 . 8Y.I
DIGESTIVE SYSTEH 1 2 l l D 0 4
2.8%1 5.6iO 2.87.1 2.87.1 I O.0Y.I O.0Y.I 11 . llO
DYSPEPSIA/HEART~H 0 l 1 0 0 0 1
0.0%1 2.8)0 2.87.1 0 . 0Y.l I O.0iO O.0Y.I 2.8Y.I
DIARRHEA l l 0 0 0 0 2
2.8%1 2.8i0 O.OY.I 0 . DY. I I O. 01. I 0.0%1 5.6Y.I
NAUSEA l 0 0 l D 0 2
l?.8%1 o.o;o 0.07.1 2.87.1 0.D7.l o.o;o I 5.6iO 0
0
NERVOUS SYSTEH l
2.8%1
0
0.OY.I
0
0.07.1 •
O.0Y.I
0
o.o;o
0
0.07.1
1
2.8Y.I
_..,
N
0
VERTIGO/DIZZINESS l
2.8Y.I
0
0.0)0
0
0.OY.I •
0. 0Y.I
0
0 , 0)0
0
0 .DY.I
l
2.8iO
Table 4 (cont)
RECOHBINAIIT HEPATITIS 8 V"CCIIIE
STUDY 07'18
TRUTNENT
LOT NUtlBER CK446
DOSE 20 t1CG
PATIENT CUSSI HEALTH CARE PERSM4EL
I TOTAL VACCJltEES t 36 PATIEHTS I - DOSE l I

1----------------------------------------------------------------------------I
I DAYS POST VACCIN"TIOII I NUN8ER
CLINICAL
COHPLAIHTS
l----------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I 5 I
MITH
ICotlPUIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------1----------l----------l----------l----------l----------l----------l-----~----I-----------
PERSONS MITH COIIPUIHTS I 10 I 7 I 6 I 4 I O I O I I 17
I I 27.8½J I I 19.4?.I I I 16.7½1 I I 11.l?.I I I O.OXI I I 0.0½1 I I I 47.2½1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS MITH HO CottPUIHTS I 26 I 29 I 30 I 32 I O I O I I l9
I I 72 . 27.1 I I 80.6?.) I I 83.37.1 I I 88 . 9?.I I I o.o;o I I O.OXI I I ( s2.e;o
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS MITH IIO DATA I o I o I o I 0 I 0 I o I I o
I I D.OXI I I D.OXI I I 0.07.1 I I D.OXI I I O.OXI I I 0.07.1 I I I O.Or.l
0
0
..,N
-
Table 4 (cont)
PATIENT COUNT CLINICAL Cot1PUIHTS
RECOtlllltlANT HEPATITIS B VACCIIIE
STUDY 0798
TRUT11ENT
LOT mt'BER CK446
DOSE 20 l1CG
PATIENT CUS!I HEAL TH CARE P[RSONHEL
I TOTAL VACCIIIHS C JS PATIENTS) - DOSE 2 I

l----------------------------------------------------------------------------1
CLINICAL
COttPUINTS
1----------------------------------------------------------------------------f
I O • 1 • 2 • l I 4 I s I
MITH
IC011PUINTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••••••••••I••••••••••
• I I I I I I I
REACTION, LOCAL UHJECT. SITU • 8 • 1 I 2 I O I O I O • I 9
• I 25.0iO • I 3.liO • C 6.3%) I C O.OY.I I C O.OiO I I o.o;o • I C 28.lY.I
-----------------------------------1----------•----------•----------•----------l----------l----------•----------I-----------
PAIN I 2 I O I O • 0 I O f I • I 2
I c 6.J?.) I I o.or., I c 0.0%1 I c o.ox1 I c o.ox, I c a.ox, • I c 6.:sx1
• I I I I I • I
SOAENESS I 6 I 1 I 1 I O I O • 0 • • 6
• I 18 . 8l!I • I J.UO I C l.UO • C O.Ol!I I C O.OY.I • I O.Ol!I I • C 18.8Y.I
I • I • I • I I
TENIERHESS I o I o I 1 I o I o I o I • l
I t G.OY.I I C O.OY.) I C 3.1)0 I I o.o:o I I 0.1)0 I I o.o:o I I I 1.1:0
---------
sysn111c
·-------------------------l----------f----------•----------l----------l----------l----------l----------•-----------
I l f 2 I J I 2 I O I D I I 9
I C 9.4l!I I I 6.Jl!I I C 9.4%) I I 6.ll!I I C O.OY.I I C o.Ol!I I I I 28 . lY.I
MtOLE BODY/GENERAL l 1 0 0 0 D 4
9 .4)! I I 3.1)!) ( _o.o:o C O. Ol!I ( O.OY.I ( O.Ol!) I 12.SY.)
fATIGUE/WEAKHESS 1 0 0 0 0 0 1
l.lY.) I 0.0)!) ( o.o:o ( O.Ol!I ( O. OY. l f O.OY.) I 1.1:0
ltEAOACHE 2 l 0 0 0 0 l
6.JiO I 3.1?.) C O.OiO C o.o;o I O.OY.I C O.OY.I ( 9.4XI
INTEGtliENTARY SYSTEN 0 0 1 1 0 0 2
0.0?.I I 0.0)0 C 3.1)!1 ( 3. ll!I ( o.o:o ( O.OY.I C 6.:SXI
RASH , NOS 0 0 0 1 0 0 l
0 .O?. I ( 0.0?.) ( 0.0)!) C 3.ll!I I o. 07.1 C 0.0)0 I 3.lY.1
OTHER 0
1.0)!) (
0
0.0)!) C
l
J.UO C
•
O.O?.I • C
I 0
0. 07.l C
0
o.o;o (
l
J.ll!I 0
0
RESPIRATORY 0 0 l 1 • 0 0 2
rv
....,
0.0lO I o.o:o ( 3.ll!l ( 3.ll!I I C• O.Ol!I ( O.Ol!I ( 6.3?.I N
Table 4 (cont)
PATIENT COUNT CLINICAL CONPLAlNTS
AECOl'EIIIAHT HEPATITIS B VACCIIIE
STUDY 0798
TREUl1ENT
LOT NU118ER CK446
DOSE 20 t1CG
PATIENT CLASS: HEALTH CARE PEASOtl'fEL
I TOTAL VACCitlEES C 35 PATIENTS I - DOSE 2 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUNSEA
CLINICAL
COl1PUIHT'S
l----------------------------------------------------------------------------1
I O I 1 I 2 I 3 I It I 5 I
WITH
IC011PLAIHTS
••••••••••••••••••••••••••••••••••• ••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I
AHitfITIS
•
o.0Y.I
I
I c
0
0.0%1
I
IC
l
J.lY.1
I
I c
0
0.0iO
I
I I
0 I
o.o;o I c
0
o.ox1
I
I
I
I c
l
3.lY.I
I I I I I I I
PHARYNGITIS f SORE THROAT I
•
•• 0Y.I
I
I(
0
O.0iO
I
I (
0
o.ox1
I
I c
l
3.liO
I
I I
0
0.OY.I
I
If
0
11.0Y.I
I
I
I
I l
l
J.lY.I
I I I I I I I
ttJSCULOSKELET AL 0 I 1 I 1 I 0 I 0 I 0 I I 1
o.o:o I c 3.lY.1 Ic 3.lY.I I ( 0.0Y.I I( o.o:o I, 0.0Y.I I
I' J . 1)(1
ARTHAALGIA, NOHOAATICUUA I O I 1 I 1 I O I O I O I I 1
I ' 0.0Y.I I I J.lY.I I ( J.lY.I I ( D,0)(I I I 0.0Y.I I ( 0.DY.I I I ( J.lY.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----- ·----1-----------
PERsoos WITH COl1PLAJNTS I 9 I '3 I 5 I 2 I O I D I I 15
I C 28.lY.1 I I 9.4Y.I I C 15.6Y.I I C 6.3Y.I I C 0.0Y.I I C 0.0Y.I I I C 46.9%1
-----------------------------------1----------l----------l----------l----------l----------1----------I----------I-----------
PEASONS WITH NO Cot1PLAINTS I 2l I 29 I 27 I 30 I O I 0 I I 17
I , 11.,i, I 1 90.6Y.I I c e1t.t•Y.I I , 9J.e;;o I c o.o;o I , e.oi1 I I c sJ.1Y.1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
PERSOOS WITH NO DATA I 3 I 3 I J I 3 I O I 0 I I 3
I c e.&Y.I I , e.6Y.I I c e.6Y.I I , e.6Y.I I c o.o;o I , o.o;o I I c a.6XI
0
0
....,
N
~
Table 4 (cont)
PATIENT COUNT CLINICAL Cot1PLAIHTS
RECOHBINAHT HEPATITIS B VACCINE
STUDY 0798
TREATHENT
LOT tlJttBER CK446
DOSE 20 tlCG
PAUEHT CLASS HEALTH CARE PERSONNEL
I TOTAL VACCINE ES I 35 PATIENTS I - DOSE 3 I

l----------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I .u1BER
CLINICAL
tOOPUIHTS
1----------------------------------------------------------------------------I
I O I 1 I 2 I l I It I 5 I
MITH
ICOMPLAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
RUCTION, LOCAL IINJECT. SITEI I 5 I 2 I 1 I 1 I O I o I I 7
I I 14. 77.) I l 5.9;1,) I ( 2.91.) I I 2.9;() I I 0.0X) I I o.o:o I I l 20.6Y.I
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
soREHEss I 4 I 2 I l I 1 I D I O I I 6
I l ll,8XI I , 5.97.1 I I 2.97.1 I 1 2,97.1 I I 0.07.I I I o.o:o I I I 17.6iO
I I I I I I I I
NDOULE FDRHATIOH I l I o I o I o I o I D I I l
I I Z.9:1.) I I 0,0)0 I ( 0.07.1 I l D.OX) I l 0.07.1 I l D.DlO I I I 2.97.I
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
SYSTEHIC I 5 I 4 I D I O I O I D I I 7
I I 14 . 71.1 I l 11,87.1 I l O.OXI I l O,0XI I I 0.0XI I I D,DXI I I l 20,6%1
----------------------------------------------------------------------------------------------------------------------------
I
II I
WHOLE BODY/GENERAL I J J D 0 0 D 6
I 8 . 87.) I 1.17.1 0.0)0 I D,OXI I 0.0Y.I I O. OXI 17.6)0
' I
I
SWEATING I
(
D
o.o:o
l
2.9XI I
0
o.o:o I
0
0.07.1 I
•
0 . 07.1 (
0
o.o;o II
1
2 . 9)!1
FATIGUE/WEU<HESS I l
' 0 D 0 0 0
I
I l
2.97.I t.O?.I I O,OiO I O.0lO 0.0?.I I 2.97.I
' ' 0.DXI (
HALAi-SE I 0
O.0XI
l
2.9XI I
0
O.OXI I
0
0,0XI I •
0.07.) I
0
0.0XI I
1
2.9)0
HEADACHE I 1
' 1 0 0 0 0 2
2,9)0 I 2. 91.) I O,0XI I O.OXI I 0.01.1 I O.OXI ( 5.91.)
ACHitfESS I
I
l
2.9)!) ( •
,.ox, 0
0.117.1
0
0.OXI
0
o. 07.1 (
0
0.07.)
1
2.9)0
'
(
CHEST TI&HTNESS I 0 1 0
' 0 0 0
' 1 0
o.o;n ( Z .91.1 o.o:o 0,0)O ( o. 07.1 ( 0.07.J ( 2. 97.I
' '
( ;:,
IHTEG'-'1EHTARY SYSTEH I l
2,97.1
0
,.o;o
0
o. o:o
0
o.o::o
0
0.0)0
0
0.0)0 I
1
2.97.1
"'.c:o
--4
' ' ' ' ' '

Table 4 (cont)
RECOHBIHANT HEPATITIS 8 VACCINE
STI.QY 0798
TRUTnEHT
LOT NUIIBER CK4ft6
DOSE 20 ltCG
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I 35 PlTIEtlTSI - OOSE 3 I
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUt18ER
CLINICAL
CottPLAIHTS
l----------------------------------------------------------------------------1
I O I l I 2 I 3 I ft I 5 I WITH
IC011PUJHTS
•••••••••••••••••••••••••••••••••••l••••••••••I•••••••••• •••••••••• ••••••••••l••••••••••I•••••••••• ••••••••••I••••••••••
I I I I I
URTICARU/lflVES I 1 I O O O I O I O I 1
2. 9)0 I I O. OY. I I O. OX I I O, OY. I I ( 0. OX I I I O. 07. I I I 2 . 9Y. I
I I I
KJSCULOSKELETAL I l O O O I O o I l
I 2. 9i0 ( 0. OY. I I O. OX I I II. OY.l I I O. OY. I I O. OY. I I I 2. 'I?. I
I I
NECK STIFFlfESS I 1 O O o I O O I 1
t.9ZI ( 0.0,0 ( O.OZI I O.o:o I I O.OlO I 0.0,0 I I 2.9i0
I
DIGESTIVE SY!ITEH I O 2 o O O o I t
O.DZI ( 5.9Y.I ( 0 . 0,0 I o.o;o I 0,0)0 ( 0.0%1 I I S.9Y.I
I
DIARRHEA I O t O O O O I t
o.o;o C 5.9)0 I 0.0½1 I O.DY.I I O.OY.I I 0.0)0 I I S.9Y.I
I
NAUSEA I II 1 0 0 0 0 I 1
( O.OY.I C 2.9Y.I I 0.0)0 I 11.0Y.I I O.OY.I ( o.o;o I I 2.9Y.I
I
VONITING I O 1 0 0 0 0 I 1
I ( O• DX I I 2. 9Y. I I O. OX I ( 0. OX I I O. OY. I I O• DX I I ( 2. 'liO
-----------------------------------l----------t----------l----------l----------l----------l----------l----------l-----------
P£RsONs WITH COMPUIHT!I I a I 6 I 1 I 1 I o I o I I 10
I I u . sr.1 I 1 11.61.1 I , 2.n1 I , t.•::r.1 I c 0.0:1.1 I I o.o:o I 1 1 n.1tr.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONs w1m HO cottPUINTS I 26 I 211 I 33 I 33 I o I o I I 24
I ( 76. SY. I I I 112. 4)0 I I 97. uo I I 97. lY.1 I I O• OY. I I I D. ox I I I I 70 . 67. I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONs WITH 110 DATA I 1 I 1 I 1 I 1 I o I o I I 1
I I 2.9Y.I I I 2.97.1 I I 2.97.1 I I 2.9Y.I I I O. DY.I I I D.DXI I I I 2.9½1
0
0
...,
:v
1.11
Table 5
PATIENT CotMT HAXIHLl'I TEHPERATURES
RECOtlBINANT HEPATITIS 8 VACCINE
STIJOl 0798
TRElTHEHT
LOT ll.JllllER CK446
DOSE 5 '1CG
PATUHT CUSS HEALTH CARE PERSONNEL
• TOTAL VlCCINEES ( 36 PATIEHTSI - DOSE 1 I

•---------------------------------------------------------------------------------------1
• DAYS POST VACCIHATIOH I tu1BU
HlX TEHPERATURE
I DEG f, ORAL I
f---------------------------------------------------------------------------------------1
• 0 • 1 • t I 3 I 4 I 5 • I
WITH
I HAX TEHP
••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••••••••••••••••••••••••l•••••••••••••••••••••r••••••••••
< 99
•• 30
•I 32
•I 3ft
•I 34
•• D
II D
II II 28
'17. l?. l I 1 97. uo I I u. o;: 1 I I o. DX, I
I 1 88. 2:0 I , '11. 4;0 I , I 1 80. o;: 1
I I I I • I I I
99 - 99. 9 I 4 I 3 I 1 I 1 I D I o I I 7
I I U.8lO I 1 8.61.1 • c z.q:o I 1 2.,:0 I 1 0.0;:1 I I o.u;:1 I I , 20.0;:1
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEHPERATURE TAKEN I 14 I ➔s I n I 1s I D • o I I 1s
I 1 94.4?.I t 1 97.21.1 I c 91.2;0 I 1 91.2:0 I c o.a;:1 I 1 0.0;:1 I I , 91.2;0
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TEl1PERATURE NOT TAKEN I 2 I 1 I 1 I 1 I 16 I 16 I I 1
I I 5.6?.I I I 2.&;!I I I 2.87.1 I I 2.8:0 I UDO.DY.I I 11D0.D1.1 I I I z.a;o
0
0
N
.....
0-
Table 5 (cont)
PATIENT COUNT HAXItlUlt TEMPERATURES
RECOHBINAHT HEPATITIS B VACCUIE
STU>Y 0798
TREATtlEtn
LOT HUtlBER Cl<446
DOSE 5 t1CG
PATIENT CUSS HEALTH CARE P(RSOHNEL
I TOTAL VACCIHUS I 36 PATIEHTS I - DOSE 2 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I NUt1BER
HlX TEMPERAT\JRE
I DEG f, ORALI
l---------------------------------------------------------------------------------------1
I O I 1 I 2 I 3 I 4 I 5 I I
WITH
I t1AX lEHP
••••••••••••••••••••••••I•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• ••••••••••I••••••••••••••••••••
NORMAL I 1 1 l l D O 1
J.3'0 I :S.2,0 I J.4Y.I I :S.1%1 I 0.0Y.I I O. 0l:I I 3.17.1
< 9'J I 25 211 26 27 l o 23

83.llO I 90.JY.I I 89, 7%1 I 81t.4%1 Cl00.0Y.I I 0.07.1 C 71.97.1
99 - 99. 9 I 2 1 2 4 o o 6
6.77.) I 3.2Y.) I 6 . 9)0 I 12.51.) I a.DY.I I o.o;o I Ul.8i0
100 - 100. 9 I l O D O O O 1
3.3%1 I 0.0i!t I 0.0%) I 0.0Y.I I 0.0Y.I I O.Oi!I C J.17.t
101 - 101. 9 I l l O D D o 1
I C :S.li!t C l.27.I I I 0 . 07.t C O.0Y.t I 0.DY.I I I 0 . OY.I I l 1 . 1:0
------------------------l----------l----------l----------l----------l----------l----------1---------------------1-----------
nHPERATURE TAl<EH I 30 I 31 I 29 I 32 I l I O I I 32
I 1 83.liO I c 86.lY.t I c eo.,z1 I , ea.,x1 I , 2.ex, I I o.o:o I I I ee.,i,
------------------------1----------1----------l----------l----------l----------l----------l---------------------l-----------
nnPERATURE NOT TAKEN I 6 I s I 7 I 4 I 35 I 36 I I 4
I I 16 . 7iO I I l3.9Y.t I I 19.4%1 I I 11.lY.t I I 97. 2Y.I I 1100.0;0 I I I 11.lY.t
0
0
...,"'...,
Table 5 (cont)
PATIENT COUHT HAXIl1Utt TEMPERATURES
IUC011BIHANT HEPATITIS 8 VACCIIIE
SlU>'f 0798
TRtAntENT
LOT t-MIBER C1<446
DOSE 5 tlCG
PATIENT CLASS: HEALTH CARE PfRSOHN£l
I TOTAL VACCINEES I 36 PATIENTS, - DOSE 3 I

l---------------------------------------------------------------------------------------1
I DAl'S POST VACCJHATIOH I tlUNBER
11AX TEHPERATUR! 1---------------------------------------------------------------------------------------I WITH
I DE6 f, ORAU I O I l I 2 I 3 I 4 I 5 I I I HAX TEHP
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••I•••••••••• •••••••••• ••••••••••l••••••••••I••••••••••
I
NORMAL • 6 I 6 I 6 6 I D O I 6
18.87.1 I I 18.87.l I I 18. 27. I I 18.8i0 I I O.DiO I 0. 07.l I I 18.2;0
I I I I
< 99 I n I 23 I 25 25 I o o I 21
71.97.1 I I 71.97.1 I I 75.87.) I 78.UO I t o.o:o I 0.07.) I t t.1.67.)
I I I I
99 - 99.9 I 3 I 2 I 2 1 I o o I 5_
- 9.47.1 I I 6,37.) I I 6.17.) I 3.17.1 I I O.Oll I o.o;o I I 1s.2:o
I I I I
100 - 100. 9 I O I 1 I O D I D O I 1
I I 0.07.) I I 3.11.) I I o.o,o I o.o;o I I D.07.1 I I 0.07.) I I 3.07.)
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEHPUATUIU' TAKEN I ]2 I 32 I JJ I 32 I O I O I I 33
I I 88. 9)0 I ( 88. 97. l I I 91. 77. t I ( 88. 97., I I O. 07. I I I 0. 07.1 I I I 91 • 77. I
------------------------1----------1----------I----------I----------I----------I----------I----- . -------------- 1-----------
TEHPERATURE NOT TAKEN I 4 I 4 I 3 I 4 I 36 I 36 I I 3
I I 11.17.1 I I 11.17.1 I I 8.3:o I I 11 . 17.t I 1100.01.1 I 1100.01., I I I 8.1;0
0
0
N
......
OD
Table 6
PATIENT COUNT MAXI~ TEMPERATURES
RECOtlBINANT HEPATITIS B VACCINE
STUOY 07911
TREATMENT
LOT IM1BER CK446 .
DOSE 1D t1C6
PATIENT CUSS HEALTH CARE PERSOMIEL
I TOTAL VACCINEES I 37 PATIENTSI - DOSE l I

l---------------------------------------------------------------------------------------1
f DAYS POST VACCIHATIOH I tlUMBER
nax TEHPERATURE
I DEG F, ORAL I
1---------------------------------------------------------------------------------------•
I O I 1 I 2 I l I It I 5 I I • HAXWITH
TEMP
••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 I 211 I 33 I 11 I 12 I o I o I I 26
I , 11.a;o I , 91.1x1 I , a,.1x1 I , 9't.lio • , o.or.1 I , o.ox1 I I , 12.2;0
I I I I I I I I
99 - 99.9 I a • 3 I s I 2 I o I o I I 10
I , 22.2x1 I , a.1,0 • , 13.97.1 I , s.97.J I , o.o:o I , o.or.1 I I , 21.a;n
------------------------1----------1----------l----------1----------I----------I----------I---------------------I-----------
TENPERATURE TAKEN I 36 I 36 • 36 I 34
I c n .1;0 I c 97. ll! t I c 97. 1io I , n .
•
,x , I c
O I O I
o. ox I I c o. or. 1 I
I 36
I 1 97. 1x,
------------------------l----------1----------l----------l----------l----------l----------l---------------------1-----------
TEt1PERlTURE HOT TAKEN I l I 1 I 1 I 3 I 37 I 37 I I 1
I I 2. 7i0 I C 2. 7l0 I I 2. Tl.I I I 8.liO I U00.07.1 I 1100 . 07.1 I I I 2 . 71.1
0
0
"'
~
,0
Table 6 (cont)
PATIENT COUNT NAXIl1Utt TENPERATURES
REC0t18IHAHT HEPATITIS 8 VACCINE
STOOY l 0798
TRUTNEHT
LOT Hllt1BER CK446
DOSE 10 NC&
PATIENT CLASS: HEALTH CARE PfRSM'El

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH • NUM8ER
HAX TEMPERATURE
IDEG f, ORALI
l---------------------------------------------------------------------------------------1
I o I 1 I 2 I J I It I 5 I I I HAXMITH
TEHP
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l••••••••••I••••••••••
I I I I I I I I '
< 99 I n I 21t I u I u I • I o I I 22
I , eo.e:o I 1 9,.oio I 1 117.s:o I , ae.9;O I I o.o:o I , o.o:o I I , 75.9:!I
I I I I I I I I
99 - 99. 9 I s I 1 I J I J I • I o I I 7
I 1 1,.21.1 I I tt.oio I 1 12.s:o I 1 11.1i1 I I o.o:o I , o.o:o I I 1 21t.uo
------------------------l----------1----------l----------1----------t----------l----------l---------------------l-----------
T£NPERATIJ!E TAKEN I 26 I 25 I 2't I 27 I I I O I I 29
I I 70.31.1 I I 67.61.1 I I (,ft.91.I I I 73.01.1 I I 11.11.1 I I 0.01.1 I • I 78.4:!I
------------------------l----------1----------l----------l----------l----------1----------1---------------------1-----------
lfHPERlTURE HOT Tll<EH I 11 I 12 • 13 I 111 I 37 I J7 I I a
I I 29.71.I I I 32.41.1 • I 35,liO I I 27.0JO I CI00.01.1 I noo.o:o I I I 2l.6l0
0
0
N
':»
0
Table 6 (cont)
PATIENT COUNT NAXIltJtt TENPERATlRES
RECotlBIHAHT HEPATITIS B VACCitlE
STUDY 0798
TRUTnENT
LOT HUt1BER CK446
DOSE 10 11CG
PATIEtlT CUSS HEALTH CARE PER~El
I TOlAL VACCIHEES I 37 PATIENTS) - DOSE 3 I

l---------------------------------------------------------------------------------------1
I DATS POST YACCIHATIOH I HUttBER
NAX TEHPERATURf
I DEG f, ORAL I
l---------------------------------------------------------------------------------------1
I O I 1 I 2 • l • 4 • 5 I I I NAXMITH
TEMP
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•-••••••••••••••••••I•••••••••••••••••••••
NORNAL I l I l I l I 1 0 I 0 I I l
I c 2.9:O I c 2.9?.I I C 3.0?.) I c 3, 0?.I I• I o.o;n I c o.o;o I I C t.9?.t
I I I I I I I I
< 99 I 27 I 31 I 30 I 28 I 0 I 0 I I 23
79.4XI I C 91.tlO I C 90,9l!I I C 84.&lO I I o.o;o I c 0.0;:i:1 I I C 67.6?.I
I I I I I I I
99 - 99 . 9 I 5 I t I 2 I 4 I 0 I D I I 9
c 14. 7:'.I I C 5.9Y.I I I 6.ll!I I C 12.1:'.I I I 0.0l!I • C o.o;o I I C 26.5l!I
100 - 100. 9 I l I o I o • I I O I o I I 1
I C 2 . 9lO I I 0.01.I I I 0.01.1 I I 0.01.1 I I 0.0l!I I I D.DZI I I I 2.tl!I
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TENPERATURE TAKEN I 34 I 34 I 33 I 33 I O I O I I lit
I I 91.9?.I I I 9l.9ZI I I 89.2l!I I I 89.21.1 I I D.o:o I c D.01.1 I I I 91.9XI
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TEHPERA1URE HOT TAKEH I 3 I 3 I 4 I 4 I 37 I 37 I I l
I I 8.1:'.I I I 8.1?.> I I 10.8lO I I 10.a;o I 1100.Dl!I I 1100.0lO I I C 8.lXI
0
0
N
-
OIi
Table 7
PATIENT COUNT HAXll?Jlt TEHPEAATURES
RECot18INANT HEPATITIS B VACCINE
STUDY 0798
TREATMENT
LOT t!Ut'IIER Ck446
DOSE 2D ttCG
PATIENT CUSS HEALTH CARE PERSOMtEL
I TOTAL VACCINEES C 36 PATIENTS) - DOSE 1 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I NU118EA
nAX TEHPERATURE
1DEG F, ow AL I
1---------------------------------------------------------------------------------------I
I o I 1 • 2 I 3 I " I s I • I nAxWITH
nnP
••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l••••••••••I••••••••••••••••••••••••••••••••
I I I I I I I I
< '19 I 29 I 34 I 33 I n I o I o I I 28
I t eo.6:0 I t ~.47.1 I C ~.37.1 I t 'f't,37.1 I t o.o;o I I o.o;o I I I 77.8,0
I I I I I I I I
9'1 - 99. 9 I 6 I 2 I 1 I z I o I o I I 6
I I 16. 77. l I I 5. 67.) I I 2. 9)0 I C 5. 7Y. I I C O. 07. I I I O. 07. I I I I 16. 71. l
I I I I I I I I
100 - 1oo. 9 I 1 • o I l • o I o I o I I 2
I I 2,87.1 IC 0.07.1. C !.97.) IC 0,07.1 I C 0.01.1 I I 0.01.1 I I I 5,67.I
------------------------l----------l----------•----------l----------l----------1----------1---------------------l-----------
unPERATURE TAKEN I 36 • l6 I 35 I 35 • 0 I O I I 36
I uoo .o:o • 1100.01.1 • C 97.21.l I C 97.21.1 • C 0.07.1 I I 0.07.) I I 1100.01.1
------------------------l----------1----------I----------I----------I----------I----------I---------------------I-----------
TE11PERA~E HOT TAKEN I O I 0 I l I 1 I 36 I 36 I I 0
I c 0.01.1 I c 0.07.1 I, 2.81.1 I c 2.8:t.1 I 1100.ox, I 1100.01.1 I I c 0.01.1
0
0
rv
0,
rv
Table 7 (cont)
PATIENT COUNT HAXIttUtf TENPERATURES
STUDY 0798
TREAfflEHT
LOT MH!ER Ct<446
DOSE 20 MC&
PATIE'HT qASS HEALTH CARE PERSONNEL
I TOTAL VACCIN£ES 4 35 PATIEHTSI - DOSE 2 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION • NUl18ER
tlAX TEHPERATURE
I DEG F, ORAL I
1---------------------------------------------------------------------------------------•
I O • 1 I t I J I 4 I 5 I I I ttAXWITH
TEHP
-••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
I • I I I I I I
< 99 I u I 21 I 28 I 26 I o I o I I 26
I• 9J .1x1 I• 96.4lo I I n.J:o I• 89.no I• o.o:o I I o.o:o I I• eJ . 9:o
I I I I I I I I
99 - 99. 9 I 2 I l I l I 2 I o I o I I 1t
I( 6.97.1 II J.67.1 I I J.J7.I II 6.97.1 II 0.07.1 I I 0.07.) I II 12.97.1
I I I I I I I I
100 - 100. 9 I a I o I l I 1 I o I o I I l
II 0.01., II 0,07.1 I I J.JXI II J.47.1 II o.ox1 I I 0.07.1 I II J.27.1
------------------------l----------l----------l----------l----------1----------l----------l---------------------1-----------
TEl1PERUIJIE TAl<EH I 29 I 28 I 30 I 29 I O I O I • :n
I I 82.97.) I I 80.07.1 I I 85.77.1 I I 82.9)0 I I 0.07.1 • I O.OlO I I I 88.67.I
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TE11PERATl-"E HOT TAl<EH I 6 I 7 I 5 I 6 I 35 I 35 I • 4
I I 11.11.1 I I 20.ox1 I I 14.37.I I I 17.17.1 I uoo.ox1 I 1100.01.1 I I I 11,47.1
0
0
N
OD
~
Table 7 (cont)
PATIENT COUNT NAXIt,Jtt lENPERlTURES
RECot18INANT HEPATITIS B VACCINE
STUDY 0798
TREATNENT
LOT NUl1BU I CK446
DOSE 20 ttCG
PATIENT CLASS: HEALTH CARE PER!IOMfEL
I TOTAL VACCINEES f JS PATIENTS! - DOSE J I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I laJHBER
f---------------------------------------------------------------------------------------1
11AX T[t1P[RlllJRE
ID[Bf,ORlll ID I l
.............................................. I Z I
, l I, I 5 • I
MITH
INAXTEl1P
..........•..........•..........•..........•..........•.......... .......... ,
I
NIJlll1ll • ll
'J.ttiO • f
ll l
J.ZY.I I C 'J.tY.I C
11
3.lY.I I I
o•I
D.OY.I I
OI
O.OiO I
I
I C
l
1.1;0
I I I I I I
< 99 I 2, I 10 I 29 30 I o I o I I 26
82.81.1 I f 96.l!ll!I I I 93.SY.I I 9l.8i0 I I D.O?.t I f O.OY.t I I I 111.llO
I I I I I I
99 - 99. 9 I J I o I 1 l I o I o I I tt
10.lY.I I I D.Dl!I I I 'J.2'0 I J . llO I I 0.0%1 I I D.OXJ I I I U.SXI
I I I I I I
100 • 100. 9 I l I O I O D I D I II I I l
I I ].4i0 I I O.Ol!) I I O.OlO I O.Di'.I I I o.o:o I I 11.0XI I I C J.lXJ
------------------------t----------1----------l----------1----------l----------1----------1---------------------I-----------
TE11PERATURE TAKEN I 29 I 31 I JI I U I o I D I I l2
I I 112.9)0 I I 81!1.6Y.J I I 1!18.6)0 I I 91.4)!1 I I 0.0?.t I I D.D?.I I I C 91.4?.I
------------------------t----------l----------l----------l----------l----------1----------1-----------------·---l-----------
tuwERATURt HOT TAKEN I 6 I It I , I 1 I JS I JS I I 1
I I 17.lr.l I I ll."0 I I ll.ttl!J I I 8.6Y.I I 1100.DiO I 1100.11;0 I I I 8.6i0
0
0
IV
0:,
C
00285
THE IOURNA.L OF INfECTtOUS DISEASES • VOL. ISl, NO , I • JANUA.RY 1916

Cl 1916 by The Uni"ff<it~ or Chica10. All ri,hu reserved. 0022. Jl99/16l5301-0026SOI .OO
Anti-HBs Responses to Vaccination with a Human Hepatitis B Vaccine

Made by Recombinant DNA Technology in \'east
In the United StateS, 1he currently licensed vaccine against ,-accinees at low risk of exposure to this disease). many
hepatitis B virus (HEPTAVAX-B9; Merck Sharp & Dohmc, member5 of groups at rislc of contracting hepatitis B have
West Point, Pa) consists of hepatitis B surface antigen been rtluctan1 to accept this vaccine.
(HBsA1) that is purified from the plasma of chronically BecallSC or these problems, alternate sources of vaccine
infected humans. Antibodies 10 the croup a determinant arc bein1 developed. Among the first to become available
of this complex antigen effectively neutralize the various Cor human trials was a 25,000-lO,OOO molecular weight
s1.b1ypes of hepatitis B virus (HBV). as shown in a num- HBsAg polypeptide deri\'Cd by disruptinc the intact 22-nm
ber or con:rolled clinical trials (1-3). Despi1e overwhelm- HBsAg panicle with a nonionic dctercent {6). lmmu1101c•
ing evidence that documents the emcacy of this vaccine, nicity of this product was superior to that of the human
widespread acceptance by those who are 11 sreatest risk HBsAg source from which it was prepared, especially dur-
of contracting hepatitis B has been less than expected be· ing the ini1ial stases of antibody de\-clopment. More re-
cause of a number ofunrelated faaon. The plasma-<lerilled cendy a number of other vaccines that do not depend on
vaccine is expensive to pn:pa~ A number of physical and human plasma as their source or HBsA1 have been pro-
chemical inactivation steps arc used in purification. and duced (7). These include chemically synthesized peptides
extensive safety tes1in1s arc mandated by the Food and from SC¥Cral antigenic domains or the HBV, products of
Drue Administration in laboratory animals. cell cultures. recombinant DNA technology, and live vaccinia virus
and chimpanzees before the product can be marketed. In rccombinanu containin1 the HBsA1 ICM.
addition, there are of necessity ba1ch-to-b11ch variations In this paper we repon one-year follow-up data on the
in human source material. These problems would have immunogenicity and reactogenicity or a non1lycosylatecl
been surmountable in the marketing of this vaccine were HBsAg hepatitis B vac:tine, subtype adw, made by recom-
it not for two recent events that made potential vaccine binant DNA technology (Merck). The vaccine, prepared
candidates overly cautious about accepting this new prod• in the yeast Saccharomyces u"visiat {strain 215~2-3)
uct: the inc:ruscd incidence of Ouillain-Barre syndrome {8, 9) was administered in three different doses (S, JO, and
that followed administration of the swine innuenza vac- 20 Jill to an adult at-risk population.
cine in 1976 and the emeraence of AIDS in the homofQ•
ual population. The lauer problem was panicularly n:le•
vanl because HEPTAVAX-B is a plasma~erived product Subjects ■ nd Medlocls
obtained from HBsA1-posi1ive individuals. some of whom After screenin1 3S9 EmerJency Medical Service person-
are in high-rislc croups for AIDS. This raised the question nel i~ HouSton, !OS adult men (median qe, 29 ,ears; ranee,
whether AIDS might be transmitted 10 recipienu of this 22-40), determined by R.IA or enzyme immunoassay 10
vaccine. Unfonun11ely, despite numerous studies (<C. SJ that be frtt or any seromarken or hepatitis B inCcction (Ab-
eventually have refuted this hypothesis (on the basis of bott Laboratories.. Nonh Chicaso. Ill), were admitted to
the susoeptibility of reuoviruses to inactivation by the phys- the study. All had antibody tO HBsAa (anti-HBs) sample•
ical and chemical steps used in producins the vaccine and to-ne11tivc-mean (SIN) ratit's <1.4, lew:ls of antibody to
by the ~ck of 1:1.Scs of AIDs or antibody scroconversions hepatitis B core antigen (anti-HBc) <39"8 inhibition, and
to human T lymphotropic: virw type Ill obRrlled among HBsA1 SIN ratios <1.2. The$e values are subswuially be·
low the cutoff le¥ds endorsed by the manufacturers. In
addition, each participant was ftqUired to ~ scrum Inds
R«eived ror publication 21 May 1985, and in re¥ised rorm or liver enzyme (alanine aminotransferase (ALT] and
9 July 19U. uparuue aminouansferue (AST]) <SO IU/liter, as deter•
This work _ , supponcd by a 1ran1 rrom Merck & Company, mined by the Beclcman Syslml TR enzyme autoanalyzcr
Ws Point, Pennsylvania. Compuuuional usiaance was p,o,,ided (Beckman Instruments, Palo Alto, ~if). Panicipants we«
by the CLINFO Project, rundcd by aranl RR.COHO from lhe Di- in 1ood health at the time of enrollment, had not been
vision or Raearc:11 11.aoutta or the Nauoaal or
lnaiitu1CS Kcalth. previously vaccinated against hepatitis B. and had si1ned
~ tllant Dorothy Hcibers ror her cxpen usil&lna in follow· informed consent n:lcucs. The study was approved by the
in1 the subjects and perronni111 the analyses; the EIIICl1fflCY Med•
Baylor College of Medicine Human lnwesti,a1ions Com•
ical Service division or the Houston Fire l)q,artmcnt fOf' 1hcir
mittec.
consiruaive suuestions and enthusiastic suppon or the project;
a.nd Esperanza Tarallo and S1c,,cn .Rao ror 1hcir cxcellen1 techni- The JOS voluntccn wert weisht matched within 4.S kg
cal &SJistance. f9a) into three 1roups of JS. Each member of each 1roup
Please addrcu requests for reprints to Of. F. IL Hollinacr, receilled 5. 10, or 20 111 of an alum-adsorbed, DNA recom-
Dcpamnent or Viroloay ancl Epielcmioloay, Baylor Collqe or binant hepa1itis B VKCine (lot no. 914/CK-446) con1ain•
Mf!diciiie. One Baylor Plaza, Houuon, Tua, 770)0. ing 20 fig or HBsA1/ml. The vaccine wu purified from
15'
0021H,
Concis~ Comm,micatio,u 157
yeast extract by physical and chcmical methods. Hydro- Table J. Seroconversion rates of anti-HBs by time and
phobic-interaction chromatography followed by gel- dose .
exclusion chromatography was the major procedure used Time (months)
to prepare the purified antisen. The removal of yeast com-
ponenlS was demonstrated in vi1ro by immunologic Dose 2 3 I 12
methods and in vivo by anaphylactic testing in guinea pip. 5 (11 • lS) 8.6 34.3t cs .1t 62.91 97.1 au:
To deli\ler 1he inoculum, ~,: used 0.S-ml syrin1cs for the 10 (11 • 35) 28 .6 80.0 94.3 • 9C.3 97.1 97 . 1
S or JO I'& doses and 1.0-ml syringes for the 20 i,g dose. 20 (11 • 35) U.6 12.9 81.6 9C.3 100.0 100.0
All doses were administered by the same person. The vac-
NOTE. Rcsulu arc pcrccnta1a or subjects who were posi-
cine was thorou1hly resuspended before use and inocu-
tive at the noted time. Dosa arc in 14.
lated im in the deltoid re1ion with a one-inch, 23-sauge
• Vaccine was administered at months 0, I. and 6.
needle at months 0, l, and 6. Blood samples were obtained t P < .002. S III compared with JO or 20 "'·
11 one, two, three. six, eight, and 12 months after the ini- l Four ~ ..-ho were poaitivc for anti-HB1 at ciJht months
tial inoculation (100'1. panicipation). A prcvaccination became scronqative at 12 momh1, whereas the one person who
oral temperature was obtained. and patticipanu ~ asked had IIOI responded by month I scroconYCrtcd.
to take and record their temperature with the same
calibrated thermometer 4 hr after inoculation and each
morning for the nc.u three days. They were also asked to
record any local or systemic symptoms eitpcrienced dur- or in fcction· v.-ith HBV during the study. Ten (9.S.,,) volun-
in& this time. Respanses ~ recci~ by mail from~ teers had aminotransftrUe levels >.50 JU/liter on one or
of the panicipants. more oc:casions CM:r the one-yur follow-up period. This
All blood samples were proccued within 24 hr and as- me is similar to that obser.-ed in a previous study IIOJ.
sayed for liver enzymes. The unit of measurement for anti- Muscle trauma caused by exccssiYe physical aaivity was
HBs was mlU/ml and was determined by the method of felt to be the cause of the enzyme elevations in three of
Hollinger ct aJ. {I0J. On the basis of the statistical analy- these t~n panicipants; this hypothesis was based on an AST
sis of at least 1,000 normal human sera, a value ,i.0.7 value that was hi&her than the ALT value and on cre1tine
m IU/ml on replicate samples was considered evidence of phosphokinasc levels of 47,S02, 844, and S33 IU/liter. A
the presence or anti-HBs for determination of scrocon- fourth \/Oluntcer sustained a lacerated Ii~ followin& an
version rates. This anorr lc\<el was ~S SD above the mean auto accident that occurred two weeks before the blood
value for the negative control samples. All samples taken specimen that showed elevated enzyme levels was taken.
at three and ri&ht months wen also tested for anli-HBc and three other men were takin& medications that have
and HBsAg 10 rule out unsusJ)CCled infection with HBV been repancd to cause liver damace. In the other three
thal mi1ht have occurred durinc the course of the study. (2.9"9) YOluntccn, &he enzyme le\lels had returned to nor-
Slatistical aleulations included Student's I test, McNe- mal when their blood was retested one week later. There
:r
mar's test, analysis of variance, and Duncan's multiple was nothing in their histories 10 explain these abnormal-
range test 1111. ities.
Serocon-wersion rates and 1cometric mean antibody re-
sponses for 111 panicipanu arc shown by dose and time
Results in tables I and 2. Seroconvenion ratCS " " signmc:antly
lower in the S"'I'& dose croup than in the 10- or 20-,.1 dose
No local or systemic reactions of a serious n11ure were
obsened by the \'OIUntecn. After the rU'Sl inoculatioa, 141ft
of the vaccinc:cs expcricnc:cd mild discomfort at the si1e
of injection; this fisurc was 121ft after the second and third Table 2. Geometric mean levels of anti-HBs (111I U/ml)
inoculations. Temperature elevations >I.SF above an in- by time and dose.
dividual's baseline ~I were recorded in 3.Btr., 9.31ft, and Time (months)
3.4'1a of the panicipanu after each of the three injections,
n:spcctivcly. Only rour oral iemperatures uceeded 100 F, Dose 1• 2 3 ,. I 12
the hishest of which was 101.2 F. Amons the systemic: ruc- s (11 • 351 o.1t OJl o.,i 2.ot 45.7l 10.ot
tions recorded after the initial inoc:ulation, headaches 10 (11 - 351 0.3 5.1 6.9 14.0 JIU 76.of
(10.Slfl), diarrhea or abdominal c:omplainu (9-''lt), and 20 (11 • 35) 0.4 7.3 9.C 26.4 S19.5 114.6
raiicuc (7.61ft) were noted most frequently. Rata declined NOTE. Doses arc aiwcn in 111.
substantially after the second and third injections. Such • Vaccine wu admini$tercd 11 mondu 0, I, and 6.
loc:il and systemic reactions are similar to those ob5Crved t P < .02. s l'I compared with 10 or 20 14.
among recipients of placebos in other studies (I0J. l P < .001, 5 Ill a,mparcd with 10 or 20 1'1·
None of the panicipanu showed scrolo1ical evidence I P • .03 , 10 l'I compattd with 20 1'1-
002R7
IS8 Conc:i~ Communications
groups ac two, three, and six months arter the initial in• participating in previous vaccine studies that used 40 1.1&
oculation (P < .002). By eight months all bu1 two of the or an HBsAg plasma-derived vaccine (10) and 20 or 40
participants had produced specific antibodies. One of these Jill of HEPTAVAX·B (9a), and the results were compared
two volunteers, who received S µg of vaccine, did develop by analysis of variance. No si1nifican1 differences in the
specific anti-HBs at a low level (1.3 m!U/ml) 12 months rate of decline were found between these four groups
following his ini1ial inoculation. Therefore, the total when equivalent levels of peak anti-HBs responses were
seroconvcrsion rate for the S-µg group through 12 months evaluated.
v.-as 1ooo;,, even though four other vaccinees who were posi- When geometric mean levels of anti-HBs at eight
tive at ei1ht months were negative: at 12 months; this yielded months were c:ompared for two different plasma-derived
a point prevalance rate of 88.60Jo (table I). vaccines, values ranged from 2,980 to 3,322 mlU/ml for
Geometric mean concentrations of anti-HBs were con- 40µgofvaccine to 1,975 mlU/ml for 20µgof HBsA1 [9a,
siderably lower in the group receiving.S ,-.g of yeast-derived 10) vs. 46 (S µg), 389 (10 ,-ig), and 520(2011g) mlU/ml for
HBsAg than in the 10- or 20-,lg dose groups after the first the yeast-derived product. These findings lead us to con•
month (P < .001; table 2). Similar differences were ob• elude that the lower antibody levels detected in adults
served when weight-matched croup members were com• receivinc the yeast-derived vaccine may be related to the
pared, most notably at six and eight months. No statisti• immunogenicity of the product. It is notewonhy that Dan•
ally significant differences were seen between the 10- and dolos et al. [13) reponed similar discrepancies in anti-HBs
20-1.1g groups during the first eiaht months in terms of levels between yeast• and plasma-derived vaccines, in which
seroconvcrsion rates or geometric mean levels or antibody. equivalent doses of antigen could be compared, although
At each bleeding iruerval, however, geometric mean lcv• immune responses were significantly lower with our lot
els of anti-HBs in the 10.µg group were lower than those of recombinant vaccine. Sinc:e a butyl agarose method was
seen in the 20-,,g vaccinees, and a P value of .03 was ob- used to remove contaminatina yeast antigens from the fi.
tained at 12 months (table 2). nal product in both of these studies, it is unlikely that this
could account for the reduced immunogenicity found in
our study. Two other studies (12, 14) did not permit equiva-
Discussioa lent time and dost comparisons between the two types of
vaccines. Variations between lots, dissimilarities in the lipid
The reasons for the significantly larger differences in im- content of the antigen produced in the yeast as compared
mune response seen between the S-..& aroup and the other with plasma-derived antiaen, reduced anti&enicity when
two groups in our study are not readily apparent. Lo1-to- compared with human HBsAg, and the fact that the yeast•
lot variation is not a fac:tor since the same lot of vaccine derived HBsAg is not glycosylated [7, SJ may be factors
was used to inoculate all three groups. The only known responsible for the relatively lower anti-HBs response seen
variable is the volume of inoculum administered. Thus, with the yeast-derived product. Funhcr field trials in differ-
the lower doses of vaccine not only contained less HBsAg, ent at-risk groups seem appropriate before a specific adult
but the total amount of alum administered was also re• dose of this vaccine is recommended. Nevertheless, several
duced even though the protein-to-alum ratio mnained con- small trials in humans have shown that the vaccine is safe.
stant among the three doses. Whether a finite amount of and we anticipate that durable levels of protection should
alum is essential for an optimal response cannot be ascer- be achieved ir sufficient immunogen is incorporated in the
tained in this study, but levels of alum should not vary vaccine.
significantly between batches of vaccine that use identi-
F. B. HOUJNGEll, C. L. Tl.otst, P. E. PEPE
cal doses or vaccine. It is interesting that similar muted Ikpartmtnts of Mtdicint, and Virolov
responses were not seen in another study that compared and Epidtmiolou. Baylor Colltft of
S ,-.g and 10 µg of yeast-derived HBsAg, although a two- Mtdicint; and rht City of Houston Emtfftncy
fold difference in the geometric mean levels of antibody
was reported (12). Since the RIA activity of equimolar
prcpantions of purified ycut HBsAg has been rq,oned
to vary by as much as 2.5 times (8), this mi1ht account
for the interstudy differences obse~d at critical thresh-
old levels.
.,_
Mttiical and Trvuma &rvias, Houston, Tuas
I. Szrnuness W. St-ns CE, Harley EJ, Zana EA, Oleszke WR,

As expected, a decline in anti-HBs concentration was William DC, Sadonky R, Morrison JM, Kellner A. Hep-
atitis B vaccine: demonstration of efficacy in :i controlled
observed in 96'7. o( 1he subjectS between the ei1hth and
clinical trial in a hiah•risk population in 1hc United States.
12th months. To examine the slope of this response mo~
N Ensl J Med 1911()-,JOJ:133-'1
compleiely, we determined the natural logarithms of the 2. Francis DP, Hadler SC, Thompson SE, Mayyrd JE, Ostrow
differences in tht anti-HBs levels after dividing by the num• 00, Allman N, Braff EH, o·Malley P, Hlwkins D, Jud•
~r of months between observations for each subject in son FN, Penley K, Nylund T, Christie O, Mcycn F, Moore
the three dose 1roups. Similar data wrT'C obtained for adults JN Jr, Gardner A. Ooco IL. Miller JH. R.eynolds OH, Mur-
00288
Concisr Commutticotions 159
phy BL, Schable CA, Clari:: BT, Curran JW, Redeker AG. 9. Scolniclt EM, Mel.can AA, Wesi OJ, McAlcer WJ, Miller
The p~ntion or hepatitis B with Y8c:cine: rcpon or the W J. Buynal:: EB. Clinical rval1111ion in healthy adults or
Centers for Disease Contr0I multi-ccn1er efficacy 1rial a hepatitis B vaccine made by -ombinant DH-A. JAMA
amons homOSttual men. Ann lniem Med 1912;97:362-6 1,a,;251:2112-,
3. Purcell RH, Gcrin JL Hepatitis B vaccines: a ua1us rq,on. 9a. Troisi CL. Heibcrs DA, Hollincer RB. Normal immune re-
In: Vyas QN, Cohen SN, Schmid ll. eds. Viral hepatitis. sponse 10 hepatitis 8 vaccine in paticnu with Down's syn•
Philadelphia: The Frantlin lns1i1u1e Pms. 1971:•91-SOS drome. JAMA, 1916 (m press)
c. S1~ns CE, Taylor PE, Rubinstein P, Tins RcY, Bodner AJ, 10. Hollinacr FB. Adam E, Hcibcrc 0, Mdnick JL. RcspolllC
Sarnsadharan MG, Gallo ltC. Safety of the hepatitis B 10 hq,atitis B vaccine in a younc aduh population. ra.:
vaccine. New Ens! J Med 19U;JILJ7s-4 Sanvncu W, Alter JH, Ma)'ll&l'd JE, eds. Viral bcpatitiL
5. Poiesi B, Tomar R, Ldlr B, Moore J. Hepatitis B vaccine: Philaddpbia: The Franklin lastilute Pms, 1911;451-66
evidence confirmins lack of AIDS 1ransmiuiC11L MMWR, II. Snedecor G, Cochran W. Swistical methods. Ames, Iowa:
198';33:615-7 • - State Uniwasny Press. 1967
6. Hollinacr FB. Sanchci Y, Troisi C, Dreesman QR, Melnick 12. Davidson M, KniCJIWI S. lnimunopnicity of recombinant
JL. llcspon1e to a HBsAO/odw polypeptide vaccine in a 11211 hepatitis B ¥KCinc. Lancet 1915;1:IOl-9
)Oun1 adult population fabsuact no. IA.SJ. In: Vyas G, 13. Oandolos E. Roumeliotou-Karayanais A, llic:hanlsoft SC.
Dicnslac J, Hoofna11t J, eds. V-nl hepatitis Uld liwer" dis- Papae...n1elou G. Safciy 1111d immunoscaicity of a nc:0111-
- Orlanda, Fla: Grvne and SUauoa, 198':6S6 binant hepatitis B vaa:inc. J Med Virol 1915;J7:57-62
7. Purmt RH, Gc:rin JL. Prospccu rorsecoa4aDdthird ccncr- 14. Jill W, Schmidt M, Zoulek Q, Lorbecr B. W-llskc B, Dein-
ation hepatitis B ...ccines. Hcpa10l01Y 1~;5:IS9-63 hardt F. Clinical evaJuuion of a recombinan1 hepatitis B
I. McAleer WJ, Buynat EB. Maiaeucr RZ. Wampler DE. Miller . ¥accinc. Lancet 191◄;2:il74-5
WJ, Hilleman MR. Human hcpat.itis B wc:cinc from
recombinant yusL Nature 191<C;J07:l71-IO
THE JOUkNAL OF INFECTIOUS DISEASES • VOL Ul, NO. I • JANUAllY 1916

C, 1916 lly The Uaiwcnity of Chicap. All ripu ,_..._ oaJl·lffl/1615301-4Gl'ISOI.CIO
The Epidemioloc of Cloitridium difficile with Use or a Typia& Scheme:

Nosocomiat Acquisition and Cross-Infection Amon& lmmunocompromised Palieats
Gastrointestinal disturbance, panic:ularly diarrhea, is one austcn of antibiotic-auocialed colitis haw: been norcd
of the commones1 side errec:u of the use or antibiotia. (3), and early animal studies sugcsted that envlronme11•
Up to 20'7,-25.,. or antibiotic-usoc:iated diarrhea occurs taJ contamination and aoss-infcaion sni&ht be imponant
in conjunction with a fecal isolate or CJostrldhlm diffrcilr in the ciioloey of outbraks or anu1>i0tic-usociated diar-
[JJ. This organism is the major came of pseudomcmbra- rhea 14). However, convincing eYidence for the cross-
nous colitis and antibiotic-associated colitis bu1 is also car- infective potential or C difficiJ,, as wdl as its demonstra•
ried in the cas1rointc:StinaJ tract or 2"9-4"9 of the normal tion as a predominantly nosocomial infection, has been
adult population and can be isolated from the feces of prevented due to lack or a reliable typing scheme for this
30-,._75-,. of asymptomatic neonates (2). 01J&Dism (5).
Various typing schemes ~ been 111uested (6-10).
R.a:ei"l:d for publication 23 April 1915, and in IT¥ised form Amons these, Tabllqchali et at (I) reported a well-defmed
S Au1ust 1915. scheme ror typing this orsanism on the basis of 1he incor-
This work wu supponcd by the Medical Jtaan:h Council. poration of r•SJmcthioninc: into badCrial proteins ud
Or. Heard was funded by• Georse Alwyn lleNardl lunary. Dr. ha¥t described to date nine distinct groups within tbc
Holland was funded by AIII-ICd Mictobiolos1 S)'llans Ltd. C difficile species (A-E. W-Z), as danonsuatcd by the
This 11udy would DOI haw: ·been possible without the help or radiolabelcd pro1cin profile obtained by ts1inc SOS-PACE
1hc SiNrs and nursin1 suff on Annie Zwlz. Dalziel, Ganoe!. and followed by autoradiography. We have applied this tech•
Stanmon wards in collcain1 lhe clinical specimen&. We thank
niquc ro iJolatcs obtained from a prospective six-month
them and Dn. T. A. Lister, P. F. Wric)ey, J. Galtoa, J. Wus, IC.
study or immunocompromised and general medical pa-
Briuen, and E. C. Huskiuon and Prof~ J. Malpu, M. Beatr,
and J. Dickinson for allolrina us to study their patictllJ.
tients in an attempt to assess the carriage and acquisition
Plcaac addn:sl requau ror rcpriau 10 Dr. S. Tabaqchali, Ocpan- or C dif/it:i~ among hospital patients. The errect of iso-
men1 or Medical MicrobiolosY, St. B a n ~ ' , Hospical, \Vest lation and containment procedun:s on the spread of
Smilhrirld, London, EC IA 7BE. C di/Jinlr was Ibo Studied.
~-n::rl'Y NO ~CI'IY a J,iDi EPUITIS B
~ - D BQUicerc- :r $e!-'X'bc-, C ~ s Prc:srco-
&rd ,n. Keln's:i• Baylor C.Oll..;e of '5edic:ine. Bccston, 'IX.
An &BMq/&dlt f0l}-peptide CP!'J vac:c:ine ard • ceca.bi-
Mnt aGI. vaccine pc-cdJced in )'eUt QoSll ace being eval-
uate-\. 'the PP ftCCW liU pcrr:ued from 22-ffa EBahJ par-
ticles, padc.ac;ed in • aicell&.c foni Aid &lU!D-«CSOd:ied.
'the at&cting nt.ed&l CNIB/40J contained 300 ~ Jt!A
eq.Jivalant en.its C?.!IJl bas«! on & SEPrAW..'<-!1 st.n:!ar:d of
100 Ba&l,,g Pm. 3 lots ccnt.&irun9 5, 1, ard O.l HBsA.g P.!U
were ~red to 2 inc.ct putic:le ftCCines. V~ina ,...
edlun..i.steced at o, 1, ard , sent.ls to 52 wight-Ntc:bed
&d.uts. P::sn:,rs~ Lo:&l &rd qstaic ruc:tioas ws:e ~
sic;nific:ant. '1'he anti-5Ba seccaxMtrsion rate at 4 WINlts
foe t.'ie 5 Jt!:1 rP vac:r:ilw Cjroup (90\I .,.,. CCIMidecAbly
better than 1::-.at MCt vith BEPtAW.X-B. IJy 12 welts, &ll
vaccine r.c:ipients in the 1 Md 5 P.!X1 P!' vaccine 9rOJ~
had sec000nwrted versus 50\ of the 0.2 Rm 9rQJP (p<D.021
'lolhich reached 100\ aeroconwrsicn by n,nth 7. 'l'hrcuc;hcut
follo,.,up, c;eaietric: man (GM) &nti-iiBS lewl.S <AIItJlmll in
the 5 Rm PP 9rcup vece si9r1ificenUy hishet than in the
other PP vaccine c;tOJEB. At 1 IOl'lth. the Q< &nti-£Ba le-.rel
foe tt-.e S R!IJ PP 9rcup WU 8.!I, WieCHS the 300 I'm NIH/40
. vaccine grcup had • at antibc:dy l~l of 5.2. By 3
n:inths, · the respective anti-!!BS lewls w,e 202 w 90,
· risl.ll9 to 1910 &rd 3450 by 7 110nths. '1be 1 &m n vaccine
pccd.ac:ed antiEBa respcnMS =np.r&ble to t.'ie 100 JtW
HEP1':>.VJ,X-B vao::ine. 'lNa, the f0lypplide vac::inea, vith
Qatanti&lly lo.we RU BB&Arg rHctivity, • pcoducad
superior anti-Hes cespcnses wherl c:arpted vith 22--nll BBa.\g
vaccines. 1bese studies canl.inl cue previcua findings in
~ that critie&l &ntiqe.'\ic deter:min&nt.1 ue
&UOCi&ted vlth these pclypetides, uw5 they provide • link
to future vaccine atuclies u i.ng synthetic: l!BMrJ
NCronolec:ul••· 'lbe rapid &nti-RBa respcnae th&~ follo.is
t.he Wtiu lno:ub.t.ion 1U99fft.S that auch &n ~ n
11i1y be benefic:iu 1n postezpcsur• prophyl.&ltia wc:c the
e.cly ~velopiwnt of ir.unity is Adv.nt.lc;e~. Prel~
inary data thcOJ¢ , 10ntha &lso vill be presented on the
i.n:unoqeruci:y ot 3 d0&es (5, 10, ard 20 n:9J ot &n l!BS,\q
vaccille lade by' reccr.ouwnt Ct._ tec:Mology 1n yeast OS>l.
Hollinger FB. Slnchez Y. Tro1s1 c. Dre1s•n &R. Melnick Jl. Innunologen1c1ty

and reactc,ven1c1ty of new htpat1t1s B v1ccin1s. Hepato]oqy 1984: 4:1027
(Abstract).
....
0
CX)
►
0
:::)
I-
v,
PROGRAM : Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,
Study 801

vaccine a1110ng health care personnel who are negative
for hepatitis 8 virus serologic markers.
VACCINE: Yeast Recombinant Hepatitis 8 vaccine

PRINCIPAL Edward J . Sept1mus, M.D.

INVESTIGATOR: Suite 740
7777 Southwest Freeway
Houston, TX 77074
STUDY LOCATION: Suite 740

7777 Southwest Freeway
Houston, TX 77074
DATE INITIATED: February 16, 1984
DAT£ COMPLETED: In progress

personnel of either sex (excluding pregnant woman),
who are negative for HBsAg, anti-HBc and ant1-H8s,
have a normal ALT level and had not previously
received any hepatitis B vaccine.
PROCEDURE: Eligible participants receive a 1.0 ml (10 mg HBsAg)

intramuscular injection of vaccine at 0, 1 and 6
months. Vaccine recipients are asked to record their
temperature da1 ly for five days after each injection
24441/871/1
1/3/86
002q1
Study 801
PROCEDURE: (Cont.) A blood specimen (10-15 ml) is obtained from each

participant approximately two weeks- before the first
vaccination. Post-vaccination blood samples are
obtained at 1, 2, 3, 6, 8, 12 and 24 1110nths. The
samples are assayed for HBsAg, anti-HBc, anti-HBs,
yeast antibody and Al T. Samples with anti-HBs titers
> 25 mlU/1111 are tested for the proportions of anti-a
and anti-t activity. -

Injection No.
22 21 21
at 7/8 110nths. 100% (21/21) of the vaccinees
seroconverted (S/N ~2. 1) and deve 1oped protective
levels of ant1-HBs (mlU/ml >10) at that t1nie.
The GMT at 7/8 110nths was - 280.8 mIU/1111 (al 1
vaccinees and responders by either cutoff).
months, 86% (18/21) were positive for anti-HBs
(111IU/ml ~10). The GMT for all vaccinees at that
time was 139.7 mIU/ml, while it was 256.0 mIU/ml
for those with a titer of mIU/ml ~10.
See Table l for anti-HBs responses for other time
intervals.
frequencies of complaints follow.
24441/871/2
1/3/86
Study 801
RESULTS (CONT.):
Frequency in S by Injection No.
In! 1 2 3
Injection 14(3/22) 10(2/21) 29(6/21)
Site
Systemic 32(7/22) 29( 6/21) 43(9/21)

complaints by injection number. Maximum temperature
data are provided 1n Table 3.
There were no serious or alaming adverse reactions
attributable to vaccination.
ALT Elevations
ALT 1eve 1s 2-7 t 1mes the upper 1eve l of nonna 1 were
observed in post-vaccination blood samples taken fr0111
three subjects. All elevations were transient and
returned to normal. None of those participants were
seropositive for HBsAg or anti-HBC. The ALT
elevations 1n two of the subjects were attributed to
infectious 110nonucleosis and cholecystitis. The third
case was asY91Pt01111t1c.
Reactions reported to the OoBRR
A 26-year old female became aware that she was
pregnant after receiving one injection of vaccine.
She experienced a spontaneous abortion at 18 weeks
after fetal death in .Y!!!:.2• No microscopic
examination was completed on the fetus. The
investigator stated the fetal death and abortion were
probably not/possibly related to vaccination.
24441/871/3
1/3/8&
Table 1
ANTIBODY RESPONSES FOllOWING VACCINATJOtl WITH RECotlBINANT HEPATITIS B VACCINE
STUDY 0801
POPUUTION HEALTH CARE PERSOlltlEL
DOSE 10 t1CG
LOT CK444
REGIMEN 0, l, ANO 6 HOIITIIS
lHllIAL SEROLOGY NEGATIVE
I Y. WITH ANTI-HBS I GtlT I MIU/HU I

Il--------------------------------------- l-----------------------------------------------------1
I I RESPOIIDEIIS I
TIHE l--------------------------------- ------1-----------------I-----------------------------------I
CtfOtlTHS I I S/N >= 2. l I t1IU/t1L >:: 10 I All VACCIUEES I SIH >:: 2 .1 I NIU/Ml >:: 10 I
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••w•••••••••••••••••••••••••••••••••••••••
1 MOIITH I 25% 15/201 I 10)( 12/201 I 0 .8 I 10.1 I 47.l
I I I I I
2 MOtnHS I 81% 117/211 I 52)( fll/211 · I 10.5 I 24.4 I 53.9
I I I I I
3 l10NTIIS I 84% (16/191 I 63Y. 112/191 I 18.8 I 37.1 I 74.l
I I I I I
6 MOHTHS I 89% 1171191 I 79Y. 115/191 I 37.1 I f,0.3 I 82.1
I I I I I
7/8 t10tl1H9 I 100% 121/211 I lOOY. CU/UI I 280.8 I 280.8 I 280.8
I I I I I
12 l'IOHlltS I lOOY. 121/211 I 86)! 118/Zl I I 139 . 7 I 1:59.7 I 256.0
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
0
0
IV
-0
~
Table 2
PATIENT COUIT CLINICAL COHPLAIHTS
RECOl1BIHANT HEPATITIS 8 VACCINE
STUDY 0801
TREATl1EHT
LOT Hllt18ER CK'tft"'
DOSE 10 ltCG
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VlCCINEES I 22 PATIENTS! - DOSE 1 I
1-------------------------------------------------
I DAYS POST VACCINATION
. -------------------------1I t«.lt'eER
CLINICAL
COt1PLAIHTS
1----------------------------------------------------------------------------I
I O I l I Z I 3 I ft I 5 I WITH
lt0t1PLAIHT9
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-I I I I I I I I
REACTION, LOCAL !INJECT. SITEI I t I 2 I 1 I 1 I O I O I I 3
I 1 9.lio I 1 9,11., I 1 't.sr.1 I I r+.s;o I I o.or.1 I I o.or.1 I I I u.,r.1
-----------------------------------1----------I----------I----------I----------I----------I----------I--
SORENESs I 2 I o I o I o I o I o I
.-------1-----------
I z
I 1 9.1;0 I I o.o;o I , 1.oY.1 I I o.or.1 I , o.or.1 I ·r o.or.1 I I 1 9.1r.1
I I I I I I I I
lEMJEAHESS I O I 2 I 1 I 1 I o I o I I 2
I , o.o;o I 1 9.uo I 1 ... sr.1 I 1 <t.sr.1 I , o.ox, 1 1 o.or.1 I 1 1 •.1r.1
I I I I I I I I
MARl1TH I 11 ol ol 01 01 01 I 1
I I ... SY.I I I 0.01.1 I I 0.0%1 I I 0.01.1 I I O.OY.I I I 0.0%1 I I I ... SY.I
-----------------------------------l----------1----------l----------l----------l----------l----------l----------l-----------
svsn111c I 4 I 2 I s I 2 I z I z I I 7
I I l8.21.1 I 1 ,.11.1 I , 22. 11.1 I 1 9.1r.1 I 1 9.11.1 I 1 ,.1r.1 I I 1 11.e:o
WHOLE BOOT/GENERAL I t
"
18.2)0 (
l
4.s;o "
( Ul.2XI I 9.UO (
1
". 57. l I
1
... s:o
6
I 1!7 , 31.1
f ATIGUE/NEAl<tfESS 1
... SiO I
D
o.o;o I
2
9.11.1 I
2
9.17.1 •
O. IY.I
0
o.or.1 "
I 18,2?.I
' ' I
NALAISE
I
1
ft.SY.I (
D
o.o,o (
D
o. or., I •
0.0%1 I
0
O.OY. I (
0
0,0%1 I
1
lt.5%1
£DENA, FACE 1 0 0 0 0 0 1
I ... SY.I I 0.07.1 I 0.07.1 I O.DY.I I 0,0%1 ( O,OiO I 4,5%1
HEADACHE 3 l 1 1 l l I
I 13.67.1 ( ... SY.I I 4.5%1 I 4.57.1 I ... s:o I 4.SiO I "
I 18,27.1
I
lCHIHESS I l 0 I 1 0 0 0 I 2
I I 4.57.1 I o. 07.1 II 4.5%1 I o.o;o I 0 .07.I I o.or.1 I ( 9.liO
0
0
I I I N
1HfECTIOU9 SlMJROHES I
I I
0
o.o;o (
D
I.D:iO
I
I I
0
o.o;o •
o.o;o I
l
lt.5%1
0
o.o:o
I
I
l
1e.s;o
-0
~
'
(
'
able 2 (cont)
PATIENT COUNT CLINICAL CONPLAINTS
RECOttBINANT HEPATITIS B VACCINE
STUOY 0501
lREATt1EHT
LOT HUIIBER CM't't
DOSE 10 t1CG
PATIENT CUSS H!AllH CARE PEA~EL
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I 22 PAlIENlSI - DOSE l I
l----------------------------------------------------------------------------1
I OATS POST VACCINATION I tu18EA
CLINICAL
COHPLAlNT9 I 0 I l I 2 I 3 I ,.
l----------------------------------------------------------------------------1
I 5 I
WITH
ICOHPUINTS
•••••••••••••••••••••••••••••••••••l••••••••••I•••••••••• •••••••••• •••••••••• •••••••••• ••••••••••l••••••••••I••••••••••
I
t10HONUCLE0515, IMfECTIOUS I 0 0 0 0 l 0 I l
I I o.o::o I ,.ox, t O.OiO I 0.0?.I I ft .57.1 I 0.07.1 I lt.57.t
I
RESPIRATORY I
I I
2
9.17.t (
•
0.07.1 I
0
o.o:o (
0
O.OY.I I
0
0.07. I I
l
It.SY. I I
2
9.UO
I
RHINITIS I 2 0 0 0 0 0 2
I I 9.17.1 I 0.07.1 I o . o:o I 0.0?.I I 11.07.1 I 0.07.t I 9.17.1
I
DYSPNEA (SHOAT Of BREATHt I 0 0 0 0 0 1 l
O.Olt I 0.0%1 I 0.0)0 I O.Olt I 0.07.t I lt.57. I I lt.57. t
ftJSCULOSKELETAL I l 0 - 0 I 0 0 0 l
lt.57.t I 0.0%1 I O.Olt I I O.Olt 0.0lO I o.o;o
ARTHRAL&JA IOTHEAI I l 0 0
I
I 0
' 0 0
I It• SY. J
l
It .57. t 0.07.1 I
DIGESTIVE SYSTEM 0
I
l
' o.oz1
1
I
I
r 1.07.1
1
I O.OiO
2
I O.OlO
2
I It. SY. I
,.
I o.o;o I lt.57.1 It.SY.I ... 57.1 I
OYSPEPSIAIJIEART8URN 0 0
' l
' 0
9.UO
0
I 9.1:0
0
I 18.27.t
1
I 0.07.t I 0.0;,:1 lt.S;,: I 0.07.1 O.OiO o.o;o It. 57. t
' I I I I
DIARRHEA
I
0
O.OlO
0
0.07.t
1
te.s;o • 0
0.0)(1
0 1
It. 57. t
'
( I.DY. I o.o;o
' I
' I
HAUSU
I
0
O.OY.t I
l
It. 57.1 ( •
0.07.1 I
•
0.0Y.l I I
1
lt.5Y.I I
l
It.SY.I I
2
9.1:0
I
AB00'1EH DISTENDED 0 0 0 l I 1 1 1
0.07.1 I o.o;o I o.o;o I 't.57.l I I 4 . 5)0 I 't.57.1 I 1t.s::o
I 0
OTHER I 0 0 I 0 0 I 1 0 1 0
0.07.t I I ' 0.0)0 I O.OY.I I I It . SU o.o:o lt.5)0 N
O.OY.t
I I ' ' -4
ORGANS OF SPECIAL SENSE I 0
0 . 0.7.t I
0
o.ox1
I
I c
1
... SiO (
0
1.ox1
I
I c
0
o.o;o I
0
o.o:o
1
4.57.J
"'
'
Table 2 (cont)
PATIENT COUNT CLINICAL Cot1PLAllfTS
RECott81NAHT HEPATITIS B VACCINE
STUDY 0801
TRUTHEHT
LOT NUIIBER CK1t4"
DOSE 10 t1C6
PATIEHJ CUSS HEALTH CARE PERsotlfEL
I TOTAL VACCINEU C 22 PATIENTS) - DOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST VACCIIIUIOH I HUt1BER
CLINICAL
COl1PLA111TS
l----------------------------------------------------------------------------1
I O I 1 I 2 I J I It I 5 I
WITH
ICot1PLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
EARACHE I O I O I l I O I O I O I I l
I1 0.0;:1 Ic 0.0;:1 Ic 1t.sr.1 I c o.or.1 Ic o.or., Ic o.or.1 I Ic 4.57.1
I I I I I I I I
HEARING JHPAIRNEHJ I· 0 I O I l I O I O I O I I l
II 0.0?.I IC 0.07.1 IC 4.SY.I I I o.o:o I( O.OY.I I( 0.01.1 I I( 4.SY.I
-----------------------------------1----------l----------l----------t----------t----------l----------l----------l-----------
PERsoos MITH cottPLAINTS I s I " I 6 I 'l I 2 I 2 I I e
I I 22.71.1 I I 18.27.1 I C 27.3?.I I I 13 .6?.I I I 9.lY.I I I 9.11.J I I ( 36.47.1
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
PERsOtl9 MITH NO Cot1PlllNTS I 17 I 18 I 16 I 19 I 20 I l!O I I 14
I I 77. 3:1. I I C 81. 87.) I I 72. 77.1 I C 86 • 4Y. J I C 90. 9Y. I I I 90. 9;: J I I C 63. 6i0
-----------------------------------1----------l----------l----------t----------l----------l----------l----------l-----------
PERSOHS WITH NO DATA I o I o I o I o I o I o I I o
I I 0.01.) I C o.o:u I C o.o:o I I 0.07.1 I C o.O?.I I I 0.0;:1 I I I 0.01.1
0
0
N
0
0-
Table 2 (cont)
PATIENT COUNT CLINICAL Cot1PLAJNTS
RECOt181NAHT HEPATITIS 8 VACCINE
STUDT 01101
lAUTMEHT
LOT IU18ER CK441t
DOSE 10 MCG
PATIENT CLASS HEALTH CARE PEASOM1£L
I
---------------------------------------------------------------------------------
TOTAL VACCitlEES I 21 PATIENTS) - DOSE 2 •
1----------------------------------------------------------------------------•
I DAYS POST VACCINATION • HlnER
CLINICAL
COl1PLAIHTS
1---------------------------------------------------------------------------I
I O • l • 2 I 3 • 4 I 5 I
MITH
ICOt1PlAIHTS
••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••••••••••••••••••••••••l••••••••••I•••••••••••••••••••••
I • I I I I I I
IIUCTION, LOCAL !INJECT. SITU I O • 2 • 0 I O I O I O I I 2
• I 0.01.1 I C 9.S?.I I I 0.0%1 I I 0.0%1 I I 0.0?.I • I 0.01.1 I I I 9.5?.I
-----------------------------------1----------l----------l----------l----------l----------•----------l----------l-----------
sMENEss I o • 1 I o I o I o I o I I 1
I c 0.01.1 • c 4.81.1 I c 0.01.1 I c 0.01.1 I 1 0.01.1 I 1 0.01.1 I I I 4,111.1
I • I I I I I I
PRUIUTIS CITCHING I I O I 1 I o I o • o • O I I l
I c o.oio I , 1t.e:o I I o.o:o • t 0.01.1 • 1 o.or.1 • t 0 . 01.1 I I , 1t.e1.1
-----------------------------------1----------l----------1----------•----------•-----
snnntc I l • 4 I 3 • 1 I
·----•----------•----------t-----------
2 I l I I 6
I, 14.11.1 • , 19 . o:o I, 14 . 3%1 I, <t.er.1 I, 9.s;o I, 4.81.1 I •1 28.6%1
WHOLE BOOY/GEHERAL I 2 4 ] 1. l l I 5
II 9.5%1 , n.o;o I 14.JY.1 lt.87.1 It.BY.I I 4.e:o I 1 n.e:o
fATIGUE/NfAKNESS
I
I l 4 3
' l
I
l l
I
I 5
lt.87.) 1 n.o:o t lit, 3%1 lt.&lO 1t.e:o I I 23,111.1
HUDACHE I 2 l l
' 0
' lt.8%1
l
(
0 ]
t 9 . 57.) I 1t.a:o ( 1t.e:o ( O.OlO ( 4.81.1 ( O.OlO I 14.3¼1
RESPIRATDtn I l 0 l 0 l 0 ' 2
I I 4.8?.I I O. 07. I I 't.llY.I I o.o:o I 4.81.1 I O.OY.I I 9.SY.I
I
IIHIHITIS I
I I
0
o. 07.1 I
0
0.01.1 I
l
4.a:o I •
O.OY.I I
l
4.87.1 I •
0.0%1 I
l
4.8¼1
I
!IIHUSITI!I I
I I
l
4.87.1
0
0.0%1
0
1.0%1
•
0.0% I I
II
0.01.1
0
O.OY.I I
1
4,8%1
,._.SCULOSKElE.TAl
I
I 0
' 2
' l
' 0 0
C
0 t
I.OlO I 9.51.1 lt.8%1 0.01.1 o . o:o
AATMRUGlA IOTHEAI I 0 2
' l
' 0
' 0
C 0.01.I
0
I 9.5¼1
2
0
0
N
0.0%1 I 9.SlO C 4.8)0
' 0.0%1 I o . o;o
' o.o;o I 9.51.1
...
.c,
Table 2 (cont)
RECOl1BJNANT HEPArITIS B VACCINE
STUOY oe01
TRUTtlEHT
LOT HUllllER CK444
DOSE 10 MCG
PATIENT CLASS HEALTH CARE PERSON-IEL
I TOTAL VACClH£U I 21 PATIENTS! - OOSE 2 I

1----------------------------------------------------------------------------I
I DAlS POST VACCINATION ( NUl18ER
CLitlICAL 1I----------------------------------------------------------------------------I
COHPlAIHTS o
,
I 1 I 2
, I 3
,
I 4
,
I 5 I
,
MITH
,I
(COMPLAINTS
••••••••••••••••••••••••••••••••••• .........• I .......... .......... I •....•.... I .......... I.......... .......... .......... ,
MYALGIA 0
o.o:o ' ( 4.87.1
I
I
l 'II
I 1
0 I 0 I
I I o.o:o I c o.or.1 I , o.or.1 I
4.87.1
0 I I
I I 4.87.1
l
I
I I I I I I
DIGESTIVE SYSTEM 0 I 0 I 0 I 0 I l
o.o:o I c o.oz1 I c 1.07.1 I f o.oz1 I t 4.87.1 I t o.o:o I
I 0 I I
I t 4.87.1
l '
I I I I I I I
A80ot11HAL PAIN9/CRAHP9 0 I 0 I 0 I 0 I l I 0 I I l
0.0lO I f o.or.1 I t o.o:o I t o.o:o I c 4.8?.I I C 0.0iO I I c 4.8?.I
DURl!HU I O I o I O I o I l I o I I l
I I o.o:o I C o.o;o I I o.07.1 I I 0.07.1 I l 4.87.1 I I o.or.1 I I t 4.eY.1
-----------------------------------1----------I----------I---------- I----------I----------I----------I ----------I -----------
PERSons WITH Cot1PUIHl9 I 3 I s I 3 I 1 I 2 I 1 I I · 7
I I 14.]ZI I I n.87.) I ( 14.3?.I I I 4.BZI I I '1.57.1 I I 4.e:o I I t 31.3:o
-----------------------------------1 ----------I----------I---------- I----------I----------I----------I----------I-----------
PERsOHS WITH HO t011PU.INTS I 1a I 16 I 18 I 20 I 19 I 20 I I lit
I , es. 11.1 I c 76. 2z I I 1 85. 1;0 I c '15. u I I t 90. 57. l I , 95. 27. 1 I I , ,.,. . r1.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH HO DATA I O I O I O I O I D I O I I 0
I I O. or. I I I I. O?. I I t O. o:o I I O. OY. I I t !I. DZ I I t D. D7. I I I I O. 07.1
0
0
rv
-0
0:
Table 3 (cont)
PATIENT C~T CLINICAL COHPLAINTS
AECottBINlNT HEPATITIS B VACCINE
STUOT I 0801
lREATMEHT
LOT NUr18[R Ck444
DOSE 10 11CG
PATIENT CLASS: HEALTH CARE PERSONN£L

I•----------------------------------------------------------------------------•
OllS POST VACCIHATI°" • tuff!Elt
CLINICAL
COHPlllNTS
1----------------------------------------------------------------------------•
I O • l • 2 • ] I 4 I 5 I
WITH
ICot1PUINTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••I••••••••••
•
IIUCTt~, LOCAL UMJECT, SITE I I ] II Z I
I
2
I
I 1
I
• 1
I
• 2
I
•
I
• 6
• l 14.37.) I l ,.57.) • I ,.57.1 I C 4.87.f I I 4.8)0 I I 9.57.f • I I 28.6Y.I
-----------------------------------•----------•----------1----------1----------1----------l----------•----------I-----------
PAIN • l • 0 • 0 • o I O • 0 • I 1
I 4.8)0 I I 0,0)0 I l 0.DlO I l D.D7.1 I I D,DY.I • l D.0)O I I ( 4.8iO
I
SORENESS 1 0 0 D 0 1 2
• 4.8Y.I l 0.0Y.) I 0.07.) I D.DlO I o.o:o ( 4.87.1 ( 9.SiO
TENDERNESS I 1 1 2 1 l 1 2
4.8Y.I 'I 4.8)0 l 9.SY.I I 4.87.1 I 4 , 8Y.I C 4.8i0 ( 9.s;o
HODUl£ FQRMATJON 1 0 0 0 0 0 1
• ... 8Y.I I 0.0Y.I l 0.0Y.I I 0. 0Y. I C 0 . 0Y.t I O,OiO C lt,8XI
PRUUTIS I ITOtING I 0 0 1 1 0 0 1
• 0.0)0 I 0.07.) I 4.87.1 I 4.8Y.) I o.o:o C 0.0Y.I I 4 , 87.I
ECCHYt10SIS I l l l 1 1 1 1
4.87.1 I 4.87.1 ( 4.87.) I 4 . 87.1 I 't,8XI I ... 87.I ( 4.8i'-I
OTHER • O I 1 I O I O • 0 I t . . l
I l 0,07.1 I I 4.87.I. l 0.07.1 I I 0.0XI I I 0.07.1 I t 1 .01.1 I I l 4.81.I
-----------------------------------l----------l----------•----------1----------l----------l----------•----------l-----------
srsn111c
I• l 14.]lO
l
II t 19.07.)
4
I• l 14.JXI
3
I• I 4 . 8Y.I
1
I• ( 9.5%1
2
II t 14.]iO
J
I• II l 42.9)0
9
----------------------------------------------------------------------------------------------------------------------------
WIIOLE BOOT/GENERAL
I
I z I• ,. II ] •I l
I
I 2
I
2 I I 8
I l '1.5)0 I I 19.0lO I l 14.])0 I I tt.ext I c 9.57.t I• l 9.5XI I • ( ]8.lXI
I
FLUSff
.•
•
• (
0 I•
o.o:o I
•
1
l
I a
4.e:o I •
I
I
I 0
•
I
a.DY.I I I
I
0
I
I
0.07.t
0
I
I
I c
•
I
• 1
0.07. I • l 0.0Y.I • .• ( 4.8i0 0
•I• I • 0
FATIGUE/llEAKNESS I 0 2 I 1 I 0 0 0 2 1\1
• C o.o:o I• C 9.sz, I 1 ... 8:o I , o.or., I• c 0.OY.t 0.01.1 • • •I • 9.57.I ,Q
-0
Table 2 (cont)
PATIENT Cota-IT CLINICAL CONPLAINTS
RECOMBINANT HEPATITIS II VACCIIIE
STUDT 0801
TREATl1EHT
LOT IIIJl18ER CK441t
DOSE 10 t1CG
PATIENT CLASS: HEALTH CARE PERSOlfl(L
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES C 21 PATIENTS)· DOSE 3 I
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I tU18ER
CLINICAL 1------------------------------· ---------------------------------------------1 MITH
COtlPLAlNTS I 0 I 1 I 2 I 3 I 4 I 5 I !COMPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••I•••••••••• •••••••••• ••••••••••l••••••••••I••••••••••
I I
HUOACHE I 0 1 I I l 2 2 I
o.o:o lt.8%1 I c Ct.8%1 I "
ACHIHESS I 2
' 2
I lt.87.1
1
I
I 0
I 9,SY.I
0
'
9.5%1
0
I
I
I 19.0l!I
3
9.5%) I 9.5%1 I 4.e:o 0.0%1 0.0%1 0.07.1 I
RESPIRATORY I 0 0 0
' 0
' 2
' 1
I
I
I 14.3Y.I
2
I I o.o::o I 0 . 0%1 I 0.0iO 0.0)0 ,.s:o I lt,87.1 9.SY.I
I ' ' I
RHINITIS I
I
0
0.0%1
• I
0
0.07.1
0
0.07.) I
I
4.8::O I
1
I
I
SINUSITIS
I
I
I
0
' 0.OlO
0 0
' 0 1
lt.8%)
0
lt.8iO
l
I I 0.0%1 I D.0%1 I o.o:o ( 0.0Y.I I 4.8XI I o.o::o I lt.87.1
I
PHARYIIGITIS CSOIIE THROATI I 0 0 0 0 2 1 2
o.o:o I 0.0%1 O.OY.I 1 o.o:o I c 9.SXI I 1t.a:o 9 . SY.l
t'AJSCULOSl<El£TAL 1 l
' 0 0 0 0
I
2
I lt.87.1 I lt.8%1 1 0.07.1 C o.o:o I o.o:o o.ou I , .s:o
AATHRALGIA IOTHERI 0 1 0 0 0
' 0 ' l
I o.ox, I 4.87.1 f 0.07.1 I 0.0%1 I o.o:o I o.o:o I 4 .87.1
HYALGIA 1 0 0 0 0 0 I
I lt.8Y. l f 0 . 0Y.I f o.o:o I ,.ox, I 0.0%) I 0.1%) I 4.e::o
DIGESTIVE SYSTEH I I 0 0 0 0 2
I 4.87.) lt.87.1 o.o::o ,.or., I 0.0%) 0. 07. I I
' ' C 9.57.1
(
A8DONIHAL PAIHS/CRAHPS 1
4 . 87.1 (
0
0.07.1 I
0
0.0)0 I •
0.07.1 I
0
0.07.) (
0
o.o:o I
1
It .87.1
0
NAUSEA I 1 I 0 0 0 0 2 0
lt.8iO I lt.8i!I C o.o::o I 0.07.1 I o.o:o ( o. 07.) f 9.57.1
""
c:,
0
UROGENITAL SYSTEH I I 0 0 0 D 0 I
lt.87.) I O.OY.l 0.0%) o.o:o 0.07.1 4.87.1
C C t.07.1 C
' '
Table 2 (cont)
PATIENT CCUIT CLINICAL CONPUitns
RECOMBIIIANT HEPATITIS 8 VACCINE
STUDY 0801
lRUlMEHT
lOT NUrl8ER CK444
DOSE 10 MC&
PATIENT CUSS HEALTH CARE PERSOHHEL
I TOTAL VACCIHEES f 21 PATIENTS I - DOSE J I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I ~ER
CLINICAL
COMPUJHTS
1----------------------------------------------------------------------------I
I O I 1 I 2 I J I It I S I
WITH
ICONPUIHTS
••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I
OTHER • 1 I o I O I O I O I O I I l
1t.e;o I I o.oY.I I f o.or.1 I I a.or., I • o.o;o I ( o.o:o I I I It.er.,
I I I I I I I
CRGANS OF SPECIAL SENSE I O I O I O I O I l I 1 I I 2
o.o:o I • o.oY.1 I I o.or., I 1 0.0;:1 I • 1t.e:o I 1 1t.a:o I I 1 9.sr.1
I I I I I I I
URACHE I 0 I 0 I 0 I 0 I 1 I O I I 1
0.0:1.1 I • o.o:o I f 0.0;:1 I • a. ox, I • 1t.ex1 I I o.ox1 I I 1 •.e;o
I I I I I I I
UE PAJN I o I o I o I o I o I 1 I I 1
I I o.oz1 I I o.or.1 I f o.oz1 I • a.ox, I 1 0.01.1 I 1 4.8%1 I I 1 1t.ex1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEPSOHS WITH CONPUIHTS I 6 I 6 I S I 2 I J I 5 I I 12
I c u.,,., I • ze.61.I I 1 2J.ez1 I 1 9.sio I 1 14.lXI I • n.ar., I I , s1.1r.,
-----------------------------------1----------l----------l----------l----------l----------l----------1----------t-----------
PERSOHs WITH t10 COMPLAINTS I 15 I 15 I 16 I 19 I 18 I 16 I I 9
• I I 71.11%1 I f 7].4)0 I f 76.Z%1 If 90.5)0 II 85.7)0 If 76.2:'.I f I I lt2.9l0
-----------------------------------1----------l----------l----------l----------l----------l----------1----------1-----------
PERSOtfS WITH tlO DATA f O I O f D I O I O I O f I 0
I f 0.0%1 I f 0.01.J I f O.OZI I I a. ox, I I 0.01.1 I I o.ox, I I f O. OXJ
C)
0
u4
-
0
Table 3
PATIENT COUNT HAXI~ TEHPERATURES
RECOttBINANT HEPATITIS 8 VACCINE
STUDY I 0801
'mEATl1EHT
lOT HUl18ER CK444
DOSE lt 11C6
PATIENT CUSS: HEALTH CAR! PERSOtlfEL
I TOTAL VACCIHUS ( 22 PATIENTS) - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUMIIER
NlX TENPERATURE
I DEG F • ORAL I
t------------------------------------•--------------------------------------------------1
I O I 1 I Z I 3 I 4 I 5 I I
WITH
I HAX TEHP
••••••••••••••••••••••••l••••••••••l••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
I • I • I I I I
< 99 I 21 I 20 I 19 I 20 I 19 I 21 I I 18
I I 95.SlO I f 90.97.l I ( 90.51.1 I ( 90.97.) I ( 90.S%1 I I 95.5?.I I I ( 81.8)0
I I I I I I I I
9'I - 99. 9 I 1 I z I 2 I 2 I t I o I I 3
I 1 4.57.1 I , 9.1:'.I I r ,.s?.1 • 1 9.11.1 I 1 ,.s;o I , 0.0?.1 I I I n.6io
I I I I I I I I
100 - 100. 9 I o I o I o I o I t I l I I 1
t 1 0.01.1 I 1 0.01.1 I r o.o;o I 1 0.01.1 I , 0.0?.1 I 1 4.s:o I . I • 4.sx,
------------------------l-·--------t----------1----------1-------·-·1------·---1-----·---·1--------------------·1-----------
TEMPERATURE TAKEN I 22 I 22 I U I 22 I 21 I 22 I I 22
I uoo.ox1 I noo.01., I , ,s.s;o I noo.o;o I , 95,5;0 I uoo.o:o I I 1100.0;0
------------------------l-----·-·--l----------l----------1·-----····1----·-·---l----------1--·------------------1-----·-·---
tE11PERATURE NOT TAJIEN I O I O I 1 I O I l I O I I 0
I C O, 07. I I f D. 01. I I I 4. 5iO I C O. 0)( I I I 4. 57. I I C 0. 07.1 I I I O. 07. l
0
0
"'
0
IV
Table 3 (cont)
PATIENT COUNT 11AXli.JN TEHPERA~ES
RECOl181NANT HEPATITIS B VACClllE
STUDY 0801
TRUTHEHT
LOT NUHBlR CK444
DOSE 10 ttCG
PATIENT CUSS HEALTH CARE PERSOHHEl
I TOTAl VACC1"£ES I U PATIENTS I - DOSE 2 I

•---------------------------------------------------------------------------------------1
• DAYS POST VACCINATION I NlftEA
•------------------------------•--------------------------------------------------------1
HAX TEHPEAATUR£
(O(GF,ORA\,, It I 1 I 2
......................................................... I l I,
, I 5 I I WITH
IHAXTE11P
,
..........•..........•..........•..........•.......... .........•
< 99 I• 20
•• 20 I• 19
II 21
•I n
•• zo I• II 17
I I 95.ZiO I I 95.27.) • I 90.5l':I I 1100.0;0 • 1100.07.1 I I 95.27.1 • I I 81.0l':I
I I • I • • I I
99 - 99. 9 I 1 • 1 • 2 I o • 0 • l • • 4
• 1 1t.&Y.1 • 1 tt.ez, • 1 ,.s;o I I o.or.1 I 1 0.01.1 I • 1t.ex1 I I , i,.o:o
------------------------•----------•----------•----------1----------1----------•----------•---------------------1-----------
TEHPERATURE TAKEN • 21 I 21 • 21 • 21 • 21 • U • • U
• 1100.0Y.I I 1100.07.1 • 1100.07.1 I 1100.07.1 • 1100.0Z) • 1100.07.1 • • 1100.07.1
------------------------•----------•----------l----------l----------l----------l----------l---------------------•-----------
TE11PERATURE NOT TAKEN • 0 I O • 0 I O I O • 0 I I O
• I 0.01.) I ( o.o:o I I 0.07.1 I I 0.07.1 I I 0.07.I I I 0.01.1 I I I 0.0iO
0
0
I.If
0
""'
Table 3 (cont)
PATIENT COUNT HAXIt1UH TEHPERATURES
RECONBitlANT HEPATITIS B VACCINE
STlllY 0801
TRUTHEHT
LOT NUMBER CK444
DOSE 10 t1CG
I TOTAL VlCCINEES ( U PATIENTS I - DOSE 3 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I HUt1eEA
HAX TEMPERATURE
(DEG F, ORA.LI
l---------------------------------------------------------------------------------------1
I O I 1 I Z I 3 I 4 • 5 I I
WITH
I HAX TEHP
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
< 99 I 16 17 I 17 I 16 I 19 I 19 I I 11
I 1 1,.zr.1 •
I ( es.or.1 I , e1.or., I ( e&.9r.1 I ( ,s.or.1 I , ,s.or.1 I I I 61.9?.I
I I I I I I I I
99 - 99.9 I 4 I l I 3 I 2 I l I 0 I I 5
I ( 19.0lO I I s.or.1 I I 14.3¼1 I 1 11.1r.1 I 1 s.or.1 I ( o.or. 1 I • ( 21.er.1
I I I I I I
100 - 100.9 I 1 I 1 I 1 I 0 I 0 I• 0 I • l
4.8?.I • ( s.or.1 I 1 4.8?.I I ( o. or.1 I ( 0. DY. I • I o.or.1 • •I ' lt.8?. I
lDl - 101. 9 I o • l I o I o I o I l I I 2
I I o.or.1 I I 5.0,0 I I 0.01.1 I ( 0.01.1 I I 0.0;:1 I I 5.01.I I I I 9.Sr.l
------------------------l----------•----------l----------l----------•----------1----------1---------------------•-----------
TEHPERATURE TAKEN I 21 • 20 I 21 • 18 I 20 I 20 I I 21
I ClOO.OY.I I I 95.ZY.I • 1100.01.1 I I 85.71.1 I I 9S.2Y.I I I 95.ZY.I I • 1100.or.1
------------------------l----------l----------l----------•----------l----------1----------1---------------------I-----------
TEHPERATURE HOT TAKEN I O I 1 I O • 3 I l • 1 I I O
I I O.OY.I I ( 4.8Y.I I I 0,0%1 I I 14,3¼1 I ( 4.8¼1 • ( 4.8¼1 I • I 0.07.I
0
0
""
0
~
-
00305

Study 803

vaccine among health care personnel who are negative
for hepatitis B virus serologic markers.

PRINCIPAL Franklyn N. Judson. M.D.

INVESTIGATOR: Denver Department of Health and Hospitals
Disease Control Service
605 Bannock Street
Denver, CO 80204-4507
SECONDARY David Cohn, M.D.

INVESTIGATORS: Denver Department of Health and Hospitals
605 Bannock Street
Denver, CO 80204-4507
Morton Davidson, M.D.
New York University Medical Center
University Hospital
560 First Avenue
New York, NY 10016
STUDY LOCATION: Denver Department of Health and Hospitals

605 Bannock Street
Denver, CO 80204-4507
DATE INITIATEO: January 16, 1984

personnel of either sex (excluding pregnant woman),
who were negative for HBsAg, ant1-HBc and anti-HBs,
had normal ALT level and had not previously received
any hepatitis 8 vaccine.
24451/861/1
1/5/86
00306
Study 803
PROCEDURE: Eligible participants receive a 1.0 ml (10 mg HBsAg)

intramuscular injection of vaccine at 0, 1 and 6
months . Vaccine recipients are asked to record their
A blood specimen (10-15 111) was obtained from each
obtained at 1, 2, 3, 6, 8, 12 and 24 months. The
samples are · assayed for HBsAg, ant1-HBc, anti-HBs,
yeast antibody and ALT. Samples with anti-HBs titers
> 25 mlU/ml are tested for the proportions of anti-a
and anti-~ activity. -
STUDY RESULTS: HEALTH CARE PERSONNEL:

Injection No.
_1_ __2_ __3_
31 30 30
One person had a 1ow titer of ant 1-HBs when the

first dose of vaccine was given.
Serolog1c data are available for 26 study
participants at 7/8 months. Eighty-five percent
(22/26) of the subjects seroconverted (S/N ~2.1)
and developed protective levels of anti-HBs
(mIU/ml ~10) at that time. The GMT for all
vaccinees at 7/8 months was 584.6 mIU/ml, while
it was 2136.0 mIU/ml for responders with titers
of mlU/ml ~10.
24451/861/2
1/5/86
00307
Study 803
STUDY RESULTS: Among participants with serology data at 12

(Cont.) months, 81% (22/27) were positive for anti-HBs
(mlU/ml ~10). At that time the GMT was 147 .1
mlU/ml for a 11 vaccinees and 513. 5 mIU/ml for
those with a titer of mlU/ml ~10.
See Table 1 for anti-HBs responses for other time
intervals.
participants following each injection. The
overal 1 frequencies of complaints are presented
below.

Comola1nt 1 2
---
3
Injection 29(9/31) 33(10/30) 30(8/27)

Site
Systemic 36(11/31) 20(6/30) 4(1/27)

complaints after each injection. Maximum
There were no serious or a larrning adverse
ALT Elevations
Four participants had transient elevations in ALT
levels (1.5 times the upper limit of nonnal). In
two individuals transient elevation occurred at
one month after vaccination, in the other two
individuals elevation occurred at 2 and 8 months
respectively. ALT 1eve ls returned to normal in
all cases. An additional individual had an
elevated ALT (1.5-2.0 times the upper limit of
normal) at 12 months after vaccination. A repeat
serology drawn two weeks later was returning
24451/861/3
1/5/86
00308
Study 803
STUDY RESULTS toward . normal. In all cases the reasons for the
(CONT.): elevations are unknown. The subjects were not 111 and
were negative for HBsAg and anti-HBc.
Reactions Reported to the OoBRR
One subject had onset of biparietal headache, upset

stomach, confusion, and expressive aphasia two days
after receiving the first injection of vaccine .
Neurologic and vital signs were within normal limits.
A CAT scan of the head was also nonna l. H1s WBC was
slightly elevated (13,000) with a shift to the left.
All symptoms resolved within 2 days. The event was
not considered to be vaccine related.
24451/86/4
1/5/86
Table 1
ANTIBODY RESPONSES FOLLOWIHG VACCINATION WITH RECOIIBltlAHT HEPATITIS B VACCIHE
STUOY 0803
POl'UL.lllOH HEALTH CARE PERSOlltlEL
DOSE 10 MCG
LOT Cl<444
l!EGIHEN 0, 1, ANO 6 tlotlTHS
INITIAL SEROLOGY NEGATIVE
I Z WITH ANTI-HBS I GMT I MIU/t1LI I

l---------------------------------------t-----------------------------------------------------1
I I I RESPOIIJERS I
TIME
I.MONTHS I
l---------------------------------------1-----------------t-----------------------------------l
I S/N >= 2. l I ftIU/Hl >= 10 I ALL V.I.CCIIIEES I S/H >= 2. l I 11IU/11L >= 10 I
••••••••••••••••••••••••••••••*•••••••••••••••••••••••••••••••-•••M••••••••••••••••••••••••••••••••••••••••••••••••
l ttoHTH or. 11212111 21?. 16/281 1.8 11.8 26.5
2 MOUTHS 76;( 122/291 62?. 118/29) 17.4 58.D 107,4
3 MOIITHS 78;( 121/271 63?. 1171271 23.8 7<t.l 131.7
6 t10UTHS 86;( I 24/281 79?. 122/28) 53.3 121,2 163.9

7/8 HOtlTHS 85?. 122/261 85?. I 22/26 I 58'f.6 2136.0 2136,0
12 t10NTHS 85?. 123/271 81?. 122127) 147.1 <tll.9 51].5
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
0
0
"",D
0
Table 2
RECOtllINANT HEPATITIS B VACCINE
STU>'I' : 0803
TilUlt1ENT
LOT HlfflER CK4ft4
DOSE 10 tfCG
PATIENT CUSS: HEALTH CARE PERSONNEL
I TOTAL VACCINEES C JI Pl TIENTS I - DOSE l I

l----------------------------------------------------------------------------1
I DAYS POST VlCCltlATIOH I HI.HIER
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I 5 I
MITH
ICCJIPUINTS
•••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••••••••••I••••••••••
I • I I I I • I
RUCTIOtl, LOCAL tIHJECT. SITU I a • J I l I O I O I O I I 9
I C 25.87.1 I C 9.77.1 I C J.27.1 I C 0.07.1 I C 0.07.1 I C 0.07.) f • C 29.07.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PAIN OH INJECTION I 1 I o • o I O I o I O I I l
I C J.t7.I I C o.07.1 I C 0.07.1 • C 0.07.l I I 0.07.1 I c 0.07.1 • I C J.27.l
I • I I I I I I
PAIN I 1 I o I o I o I o I o I I l
I c J.2x1 I c o.o;o I c o.or.1 I c o.or.1 I c o.o;o I c o.o;,o I I c 1.2,0
I I I • I I I I
SORENtsS I 7 I l I l o I
I o I o I I e
I c u.•io I c ,.1;0 I c 1.2x1 I c o.o;o I c o.or.1 I c o.o;o I I c 2s.e;o
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
svsTEt1Ic I 6 I 4 I 4 I 4 I 2 I J I I 11
I C 19.47.1 I C 12.9)0 I C 12.97.1 I C 12.9;0 I C 6.SlO I C 9.77.1 I I C :,s.s;o
----------------------------------------------------------------------------------------------------------------------------
I I
..iou BODY /GEltERAl I 4 1 2 2 I l l I 6
I C
.
12.97.) C J.27.t C 6.57.t C 6.SY.l I C J.2XI ( ].27.1 19.4%1
I I
CHILLS I 1 0 0 0 I 0 0 I 1
l . 2Y.I C o.ox, C o.o:o C 0.0lO I f o.ox, ( ,.ox, ( J.2ZI
fATIGUE/NEAKNESS I 2 1 1 1 1 1 2
6.57.1 C J. 21. t I J,2i'.I I J.2iO I J.2:0 I J.21. I I 6. SY.I
HIEADACNI! I
(
0
0.0Y.I (
0
O.0lO C
1
J,27.I (
1
:S.2Y.I C
0
0.0)0 ( •
0.01.1 (
2
6,SY.I
UGHTMUOEO I 1 0 0 t 0 0 0 1
C 'J. 2Y. I C 0. 07.1 I 0.0iO I C 0.07.1 ( 0.07.I C 0,07.1 I J.2)O
I
INTIG\JN[HTARY SYSTEl1 I 2 1 1 I 1 1 l 2 0
6.SY.I C J.27.t I J.uo I c J.tlO I J.27.1 ( l.2Y.I I C 6.SY.I 0
PlPUUR RASH I
(
1
J. 2Y. I I
0
O.OX) C
0
0.0;t.l
I
t
I C •
0.0iO C
0
o.o;o I
0
0.0ZI
I
I
I C
l
J.2ZI
...
vi
0
Table 2 (cont)
RECOflBJNANT HEPATITIS 8 VACCINE
STUDY 0803
TREATMENT
LOT NUl18ER CK4it4
DOSE 10 ltCG
PATIENT CUSS HEALTH CME PERsotl-lEL
----------------------------------------------------------------------------------------------------------------------------
( TOTAl VACCIIIEES I 'Sl PATI£HlSI - DOSE 1 I
1----------------------------------------------------------L-----------------I
CLINICAL
tOMPUIHTS
1-----------------------------------------------------------------------~----I
ICOMPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
PRUIUTIS/ITCHIHG I l I 1 I l I 1 I 1 I 1 I I l
J.2%1 I c J.2%1 I c J.ZY.J I I J.27.J I c 3.27.1 I I 3.2%J I I I J.2:O
I I I I I I I
RESPIRATORY I l I 1 I l I l I l I Z I I 2
3.2%1 I I 3.t;o I c J.ZlO I I J.27.J I 1 'J.27.t I c 6.s;n I I l 6.SiO
RHINITIS I
- ,
0
o.o;o •
0.0%1
0
0.0%1
0
0.07.1
0
O.OiO
1
J.2)O
l
J.2%1
UPPER RESPIRATORY INFECT., HOS I 1 1 1 l 1 1 l

- 3.2%J J.2%1 J.27.1 J.2:0 J. 27.1 J.2)0 J.27.1
tll!CULOStELElAL I l 2 1 l 1 1 2
- ].2)0 6.5%1 J.ZlO J. 27.1 J.2i0 J.z;o 6.SY.I
ARTHRALGJA I OTHER) I 1 l 1 l 1 1 l
J. 27., J.Z%1 J.2%1 J.2%1 J.2)0 J.2%1 J.2:0
HYALGJA I- l
3.27.J 1 1 l 1 1 l
J.ZlO J.Z%1 J.2%1 J.27.t J.2%1 3.UO
OTHER I o
0.0%1 1 D D 0 D 1
J.2%1 0.0%1 0.0%1 o.o:o 0.0%1 J.2l(I
OI6UTIVE SYSTEH I 0 0 1 0 0 0 1
0.07.t 0.0%1 3.2lO 0 . 0%1 0.01., o.a:o J.2%1
DYSPEPSIA/HURTB\MH I 0
0.07.J •
0.07.J
l
J.2%1
0
0.0%1
0
o.o;o
0
0.0%1
l
J.2%1
NERYOU5 SYSTEH I 0 1 z 1 0 0 2
1.07.J J.ZlO 6.57.1 3. 2%1 0,07.1 0.0%1 6.5%1
0
•
-
PARESTHESIAS l 1 1 0 0 l 0
0.0%1 J.ZiO J.2)O 3 . tY.l o.o;o a.ox, J.2%1 ""
THOUGltT JHPAIRl1ENT
•
o.o;o
0
O.OiO
1
J.27.t
0
o.o:o
0
0.0%1
0
0.0%1
l
J.2%1
Table 2 (cont)
PATIENT COUNT CLINICAL COttPLAINTS
RECOHBJNANT HEPATITIS B VACCJIIE
STUOY 0803
TREATMENT
LOT NUl18ER CK444
•
DOSE 10 tlCG
PATIENT CLASS HUlTH CARE PERSONHEL
I TOTAL VACCINEES I 31 PATIENTS I - DOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST VACCitlATlON I t1Ut1BER
CLINICAL l----------------------------------------------------------------------------1 WITH
COf1PLAINTS • 0 • 1 I 2 I J I 4 I 5 I ltOttPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••I••••••••••
I I I I I I I I
OTHER I 0 I O I l I 0 I 0 I O I I 1
I I O.OY.J I l o.or., I l J.2r.1 I I O.OY.I I I O.OZJ I I O.OY.I I I I 3.27.1
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
PERs0t1s MITH COMPLAINTS I n I 7 I 4 I ,. I 2 I J I I 19
I C 41.9?.I I I tt.6Y.J I I I2.9Y.J I l 12.,r.1 I C 6.SY.I I l 9.7Y.J I I C 59.ll(J
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEIISONS MITH HO COttPUINTS I 18 I 24 I 27 I 27 I t9 I 29 I I lJ
I c se.uo I , 77.4:o I , e1.1;0 I c &7.ll(J I c 9J.s::o t , ,o.,x, I I c 41.9:o
--------- ·-------------------------1----------1----------l----------l----------l----------l----------t----------l-----------
PUSOffS MITH HO DATA I O I O I O I O I O I O • I 0
I c ,.ox, I I o.or.1 I c o.or.1 I c o.or., I I o.or.1 I c ,.or., I I c o.or.,
C>
0
.........
N
Table 2 (cont)
AECOt'SINANT HEPATITIS 8 VACCINE
STUDY 01103
TREATMENT .
LOT t11Jt18ER CK44't
OOSE 10 1'1CG
PATlt:lfT CUSS: HEALTH CAA! P(ASOtflEL
I TOTAL VACCitlEES f 30 PATIENTS I - DOSE 2 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I tlU1BEA
1----------------------------------------------------------------------------I
CLINICAL
COMPLAINTS I
I
O I
I
l I
, Z
I
I
I
3 I 4 I 5 I
MITH
...................................•.......... ..........•..........•..........•..........•...•......•.......... ICCJ1PUINTS
..........
• • •
,
I
RUCTION, LOCAL IINJECT. SITEI I 7 I 8 • 5 I 3 I 2 I l I I 10
I I ZJ.liO I I t6.7t:J I I 16.7¼1 I f 10.0Y.I I f 6.77.1 I I J.lY.I I I f 33.lY.I
-----------------------------------1----------l----------l----------l----------l----------•----------I----------I-----------
PllN ON IHJECTJON • 1 I O • 0 I O • 0 • 0 I • 1
3.3Y.I • I O.OY.I • I O.OY.I I I O.OY.I • I O.OY.I • I O.OY.I I I I 3.3Y.I
PAIN
.•
I
(
1
3. lY.1
,.
I
I
I
I
0
0.0Y.I
I
I
I
I
0
o.o:o I•
I
1
0 I
o.o;o I 1
•I
0 I
o.o;o I 1
I
•
o.oY.1 I•
•
I
I
I
I
l
3. 3Y.J
SORENESS I
13.lY.I
I
I
s
I 16.7Y.J
I
I I
2
6. 71.1
I
I I
0
O.OY.) I I • I
O.OY.I I I
0
0.01.1 •I I
I
s
I 16. 7Y.I
I I I
TENDERNESS 1 I 2 I• 2 2 • 1
• 1 • •
I 2
•I f 3. JY.I • I 6 . 7Y.I I I ll.7i0 I• I 6.7)0 I• I 3.3Y.I • I J . JY.I •I • C 6.71.I
I I I
NOOULE FOAHATION I 0 I• 1 I• 1 I 1 •
I 0 I• 0 • 1
O.OY.I I I :,. 31.1 I I J.JY.I I I J. 11.1 I t o.o;o I t o .01.1 I • •• C 3. JY.I
1
LYHPHAOEHOPATHY, RE61~L • 0 I 1 I l I 1 I 1 I O I • 1
• I O. OY. I • I :S. 3)0 I I 3. 3,: I I I J. 3;0 I I 3. 3Y. I I I O. 01. I I I I J . 3)0
-----------------------------------•----------•----------l----------l----------•----------l----------l----------l-----------
s,sren1c I " I l I s I «. I 1 I 1 I I 1,
• I 13.]Y.I I I 10.01.J I I 16.71.1 I I l].3Y.I • I 3.3Y.I • I 3.31.1 I I I 20.07.J
NHOLE BOOT/GENERAL I t I t I t I 2 I 1 I 1 I I J
• I 6.7XI I I 6. 77.J I I 6. 71.1 I I 6.7Y.I • I J.3Y.I I I 1.1,:1 I • I 10.0Y.I
I I I I
FATIGUE/WEAKNESS I• 0 I 1 • 1 1 I 1 I • 1 • 1
• I o.o:o I I l.3)0 • C • J.JY.I I• I 3.3Y.I I I J.3Y.I • I l,JY.I • • I• I ]. JY. I
I I I I I I
LIGffTHEADED I 1 I 0 •I • 0 I 0 • • I I
3.3XJ I I 0.07.1 • I O.OY.I • I • O.Ol!I • I o.o:o •• • O.OY.I • • I
1
3.JY.I 0
0
I I I
ltHIHESS I 1 I 1 I• 1 •I 1 I 0 I 0 •I • 1 ....
~
J. 37. I I I J.37.1 • I 3 . 3Y. I • I 3.3Y.I I ( O.OY.I • I D.OY.I I •I C J. JY. I

""'
Table 2 (cont)
PATIENT COUNT CLINICAL CONPLAIHTS
REC0t18IHANT HEPATITIS 8 VACCINE
STUJ't 0903
TRUTl1£NT
LOT HUt18ER CK44°'
DOSE 10 ttCG
PATIENT CUSS HEALTH CARE PERSONtEL
I TOTAL VACCINEES I JO PATIENTSI - DOSE 2 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I N.HIER
CLINICAL l----------------------------------------------------------------------------1 MITH
C011PlAIHT9 1 1 I I J I I s ICOHPUINTS
D l l!
" I
•••••••••••••••••••••••••••••••••••I••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
I
IHTEGut1ENTARY SYSTE" I 1 l 1 l 0 0 l!
J. Ji:I I J. JY.I I J.JiO I J.Ji:I ( 0 .Di: I I O.Di:I I 6 . 7Y.I
PRURITIS,ITCHING I 0 1 1 1 0 0 l
D. DY.I I J.JlO I J.Ji:I ( J.Ji:I ( 0.0;:1 I 0.0;:1 I J.Ji:1
RASH, HOS I 0 l l 1 0 0 1
o.o;:, I J. JY.I I J.JXI I J.Ji:I I 0.07.1 I 0.0;:1 I J. ]i:1
OTHER I 1 0 0 0 0 0 l
J,Ji:I I 0.01.1 I O.OY.I I 0.0;:1 I 0.07.1 I 0.07.1 I J.J?.I
RESPIRATOR't I 1 0 0 0 0 0 1
J.JY.I I t.OY.I I 0.0?.I ( o.o;o ( 0.0;:1 I O.OY.I I J.JiO
UPPER RESPIRATORY INFECT., NOS I 1 0 0 0 0 0 1
J. 3%1 I O.OY.I I 0.0?.I ( o.o;o ( 0.0;:1 ( o.o;o I J.JY.I
DIGESTIVE SYSTEH I 0
D.ox, I •
o. ox, I
2
6. 7?.I I
1
S.Ji:I I
0
0.0%) C
0
o.ox, I
2
6.77.I
DIARRHEA I O I D I 2 I 1 I O I D I I 2
. I I 0.07.1 I I O.OY.) I I 6.T/.1 I I J.JY.I I I O.OY.I I I 0 . 07.1 I I I 6.77.I
-----------------------------------l----------l----------l----------1----------1----------1----------l----------1-----------
PERSONS NlTH COMPLAINTS I 9 I 10 I 8 I 6 I J I 2 I I 12
I c JD.o:o I c 11.:,1.1 I , u.r1.1 I 1 20.0;0 I 1 10.0:t.1 I 1 6.1x1 I I , 40.0;:1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsOHS NITH HD cOttPUINJS I u I 20 I 22 I 24 I 27 I 2& I I ta
I c 10.ox, I c 66.11.1 I c 11.1;:1 I I ao.o;:1 I 1 90.0:0 I c 9J.JXI I I 1 60.0;0
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I--- --------
PERsOHS MITH HD DATA I o I o I o I o I o I o I I o
I I o.o;o I C O.OXI I I O.Oi!I I I o.OY.I I I 0.07.1 I I O.OiO I I I O.OXI
0
0
..."'
~
Table 2 (cont)
RECOt18INANT HEPATITIS B VACCINE
STUDY 0801
TREATMENT
LOT NUMBER CK4't't
DOSE 10 ttCG
PATIENT CUSS HEALTH CARE PERSOMIEL

1----------------------------------------------------------------------------I
. I DAYS POST VACCINATIOH I N.JNBER
CLINICAL 1----------------------------------------------------------------------------I MITH
tot1PLA1ms I o 1 1 I z • 3 • ,. I s • •cOt1PUIHTs
••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
• I I I I I I I
RUCTION, LOCAL IIHJECT, SllE I I 7 I 't I 2 I 1 I O I O I I 11
I 1 2$.97.1 I I l't.a;o I 1 7.tt;i:1 I I J.n, I I o.ox, I , 0.0;,:1 I I 1 29.6?.I
-----------------------------------1---------- ----------•---------- ---------- __________ ,__________ ---------- -----------
PAIN OH IHJECTIOH I l O I II 11 0 I G 1
3.nn I 0.11?.J I I o.o;o I 0.0?.I I o.o;o I I o.o:o I J.TI.I
I I
PAIN I l t O D O I O 1
3. 7Y. I I O. 0?. I I O. 0?. I I O • t?. I I D. D?. I I I O. t?. I I 3. Tl. I
I
SORENESS I 5 t 1 l D I O 5
18.s:o I 7.4?.I I 3. 7?.I I :s. 77.1 I 0.DY.I f t 0.07.1 I Ul.5?.I
I
TENDERNESS • 0 t O O D I O t
0.0:1.1 I 7.4?.I I o.o;o I D.o;o I D.D?.I I I 0.0?.I I 7.lt?.I
I
WARMTH I 1 0 0 0 DI O 1
3.no I I.0Y.I I 0.07.1 I 0.0Y.I C 0.DY.I f C 0.07.I I 3.7)0
I
PR~ITI9 t ITCHING I I O O 1 0 0 f O 1
•C C
0.0?.I C 1,0XIC C 3. 7lOI I 0.01.1 0.OXI C 3. 7?.I0.01.1
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
snn111c I o I 1 I 1 I o I o I o I I 1
IC o.o;o It J,71.1 I I J.7iO IC 0.01.1 IC 0.01.1 IC o.o:o I IC J.7?.I
--------------------------------------------------------------------------------
' I I I I
...OLE BODY/GENERAL I O I 1 I l I O I O I O I I 1
I I 0.0XI It J,71.J I I J.7iO I I o.o:o I I 0.DY.I I t 0.0?.I f f I 3.7:O
• • • • I I I I
SEHSAT-JOH Of MARHTH, GEH£RAL I O I 1 I O I 0 I D I O I I 1
I I 0,07.1 I I J.7?.I I I 0.07.J I I II.Or.I I t 0.DXJ I I 0.07.J I I I J.77.1
I I I I I I I I
ILLNESS, HOS I o I o I l I o I a I t I I 1 0
I t o.o;o • , ,.ox, I t J.77.t I t a.or., I I o.or.1 I I o.o:o I I , :s.n,
-
0
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I----------- u,I
PERSottS MITH Cot1PUINT9 • 7 • It I 3 • l • D I O • I 8
I I 25.91.J • I n.e;o I I 11.1;0 I I J.7l0 I I 0.0;:1 I I 0.01.1 I I C 29.6?.I I.II
Table 2 (cont)
RECOtElNANT HEPATITIS 8 VACCINE
STUl>Y 0803
TREATl1EHT
LOT NUt18ER CK44C'!
DOSE 10 t1CG
PAlllENT CUSS HEALTH CARE PERSOMIEL
I 101Al YlCtlNEES I 'SO PITIEHTS) - DOSE 'S I

l----------------------------------------------------------------------------1
I DAYS POST VACCIHATION I IUtBER
CLINICAL
COMPLAINTS l----------------------------------------------------------------------------1
I O I 1 I 2 I 'S I 4 I 5 I WITH
ICONPLAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••••••••••••••••••••••••••••••••••••I••••••••••
-----------------------------------1----------I----------I--·
PERSOtts wnH HO COMPLAINTS I zo I n I -------l----------l----------1----------1----------1-----------
z4 I 26 I 21 I 21 • I 19
I I 74.liO I I 85.2i0 I I 811.97.1 I I 96.31.1 I llD0.07.1 • 1100.0iO • • I 70.tiiO
-----------------------------------1----------l----------l----------l----------l----------l----------•----------I-----------
PtRSOHS WllH HO DATA I Z I Z I 2 I 2 I 2 I Z I I 2
I 1 6.97.l I 1 6.97.l I 1 6.97.1 I 1 6.97.l I I 6.97.1 I· I 6.9?.l I I I 6.97.1
0
0
"'
,-
0'
Table 3
PATIENT COUNT HAXIHUH TEHPERATURES
RECotlBINAHT HEPATITIS 8 VACCINE
STUDY 0803
TRUTNENT
LOT NUIIBER CK4't4
DOSE 1D HC9
I TOTAL VACCIHEt:S ( l1 PATIENTS I - DOSE 1 I

l---------------------------------------------------------------------------------------1
1---------------------------------------------------------------------------------------I
HAX TEHPERAT~E
I DEi. F • ORAL t I O I 1 I 2 I J
I
I 4 ,
I
I 5
I
I •
I
I HAXWITH
TEHP
......................................................... ..........•..........•..........•..........•.......... ..........
I I I
,
I
< 99 I H I 27 I 27 I 27 I 29 I 26 I I Zlt
I c 90.JY.I I c 9o.o;o I • 90.01.1 I c e1.1x, I , 96.ni I , 92.9Y.t I I 1 77.4:f.t
I I I I I I I I
99 - 99. 9 I J I l I J I 4 I 1 I 2 I I 7
I f 9.71.1 I f 10.0)(1 I l 10.0Y.I I f 12.9Y.) I f ].]Y.I I f 7.lY.I I I ! t2.6:f.l
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEHPERATURE TAKEN I 31 I 30 I ]0 I 31 I 3D I 28 I I 31
I uoo.01.1 I , 96.&,o I • 96.ex, I uoo.ox1 I , 'Ht.er., I , ,o.JY.1 I I 1100.or.1
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEHPERAT~E NOT TAKEN I O I 1 I l I I I 1 I J I I O
I I 0.0)0 I l J.2U I l J.2Y.) I ( O.OiO I ( J.ZY.t • ( 9. 7Y.I I I I 0.0Y.t
..
0
1.,,1
......
Table 3 (cont)
PATIENT COUNT HAXI~ TENPERATUIES
RECOltBIHANT HEPATITIS B VACCINE
STUDY D80J
TRUTNEHT
LOT t«Jt18ER CK444
DOSE 10 ttCG
PATIENT CLASS: HEALTH CARE PER~El
I TOTAL VACCIHEES C JO PATIENTS I - DOSE 2 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I IIUHl!ER
HAX TEMPERATURE
IDEGF,DRAU
1---------------------------------------------------------------------------------------I
I I I l I 2 I J I 4 I 5 I I
WITH
IHAXTEHP
••••••••••••••••••••--••l••••••••••l••••••••••I•••••••••• •••••••••• •••••••••• •••••••••• ••••••••••l••••••••••I••••••••••
I I
HORHAL I l I O I l 1 1 1 I O
J.]1.1 I C D.01.I I C J.-.;o C J.67.) I J,67.) C J.8i!I I C ,.o;o
I I I
< 99 I 26 I 26 I 25 26 25 n I 2o\
c 86.11.1 I c 92.91.J t t 86.21., t 92.9,o c &9.3?.t t e8.s,o I t eo.01.1
I I I
99 - 99.9 I 3 I 1 I J 1 2 2 I s
10.01.1 I C 3.61.1 I t 10.31.1 C J.61.1 I 7.liO I 7.7,0 I C 16.71.1
I I I
101 - 101. 9 I O I l I O O O O I l
I t 1.01.I I C J.61.) I C 0.01.J C o.o;o I O.OlO I C 0.07.) I I C 3.31.1
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEHPERATURE TAKEN I 30 I 28 I 29 I 28 I 28 I 26 I I JD
I noo.o:o I c 91.11.1 I c 96. 11.1 I c ,1.11.1 I , 9J.J:o I c 86.n, I I uoo.o;o
------------------------l----------l----------l----------l----------l----------l----------1---------------------1-----------
TEHPERATURE NOT TAKEN I O I 2 f l I 2 I 2 I 4 I I 0
I I 0.07.1 I I 6. 77.1 I C J.31.1 I C 6. 71.1 I I 6. 7r.l I C 13.Ji!I I I I O.DXI
0
0
...
u,i
(J)
Table 3 (cont)
PATIENT COUfT "AXIt1Ul1 TENPERATURES
RECOl18IHANT HEPATITIS B VACCINE
STUDY 0803
TREATMENT
lOT NUtiBU CK44lt
DOSE 10 HCC
PATIENT CUSS HEALTH CARE PERSOtatfl
I TOTAL VACCIHHS I 30 PATlENTSI - DOSE l •

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION • NUHBER
HAX TEHPERATURE •------------------------------------------- --------------------------------------------•
I DEG F, ORAL I I O I l I 2 I l I ft I s I I I HAXWITH
TE"P
••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 I Z2 I 19 • 21 I 24 • 21 I 22 • • 19
I I 91. 71.1 I ( 79.27.1 I ( 87.57.1 I ( 96.07.1 I ( 91.17.1 I I 95. 7i0 • I I 76.01.I
99 - 99. 9
I
I 2
I
I s
II 2
•
I l
I
I l
•
I l
•
I
•
I s
II B. 11.t It 20. a;o It 8 . 37. l I t ".oz, I t ". 1r. 1 I , ". 1r., I It 20 .111.,
I I I I I I I I
100 - 100. 9 I o I o • 1 I o I 1 • o I I 1
I I 0.11,0 • I 0.07.1 I I lt.27.1 • I o.o;n I I lt.]7.1 J I O.OY.I I I I It.DY.I
------------------------l----------l----------l----------t----------t----------t----------•---------------------l-----------
n.11PERAT\JRE TAKEN • 24 • 24 I 24 I 25 • U I 23 I • 25
• c eo.01., I c eo .o;o I c 110.0,0 I c e1.1x1 I c 76.77.1 I c 76.77.1 I I , BJ.11.1
------------------------1----------t----------l----------•----------•----------l----------•---------------------•-----------
TEHPERATURE HOT TAl<EH • 6 I 6 • 6 I 5 • 7 I 7 I • 5
• I to.Or.I I I 211.0;0 • I 20.07.1 • I 16.710 I I U.J;o I I Zl.lXI I I I 16.1.'-J
-
0
\>,I
-0
00320

Study 807
PURPOSE: To tQIIIPar·e antibody and clinical responses to yeast

recOllbinant and plasaa-derived hepat1t1s B vaccine
among health care personnel Who ar negative for
hepatitis 8 virus serologic markers.
VACCINES: 1. Yeast RecOllbinant Hepatitis B Vaccine

Lot 972/C-{444 (10 IICg HBsAg/ffll)
2. Plas1111-Derived Hepatitis B Vaccine
Lot 1510J (20 IIC9 HBsAg/ml)
PRIMARY Solko w. Schalm. M.D.

INVESTIGATOR: Department of Internal Medicine
and Gastroenterology
University Hospital Dijkzigt
Rotterdam. The Netherlands
SECONDARY Dr. Rudolf A. Heytink

INVESTIGATOR: Department of Virology
Eras1111s Un1vers1ty
Rotterd111. The Netherlands
STUDY LOCATION: University Hospital D1jkt1gt

Rotterda•. The Netherlands
DATE STUDY INITIATED: ~pril 4, 1984
DATE STUDY COHPLETEO: In progress
STUDY POPULATION: The study population consists of 50-60 health care

personnel of either sex (excluding pregnant WOiien),
Who are negative for HBsAg, ant1-HBc and anti-HBs.
have a nonul ALT level and have not previously
STUDY PROCEDURE: Eligible study participants receive a 1.0 ml
intra11uscular injection of yeast recombinant (10 mcg
HBsAg) or plas111&-derived (20 11eg HBsAg) vaccine at 0,
1, and 6 110nths. Vaccine rec1p1ents record their
temperature and any local or systemic complaints for
five days after each injection of vaccine.
24731/1
1/15/86
00321
Study 807
STUDY PROCEDURE A blood saq,le is obtained from each study participant

(CONT.): approximately two to three weeks before the first
injection of vaccine. Post-vaccination blood salllJ)les
are obtained at 1, 2, 3, 6, 7, 9 and 12 110nths. Blood
samples are obtained at 24 months from those
participants who have seroconverted.
All serum samples are assayed for HBsAg, antt-HBc,
anti-HBs, and ALT. saniples may be tested for yeast
antibody. In addition, samples with an ant1-H8s titer
~25 mIU/ml may be tested to detemtne anti-t and
anti-!t subtype specificity.
RESULTS: HEALTH CARE PERSONNEL

Yeast Recombinant Hepatitis B Vaccine:
10 mcg Lot 972/C-K444 ·at 0, 1, and 6 110nths
Plas111B-Derived Hepatitis 8 Vaccine:

20 111tg Lot 1510J at 0, 1, and &110nths
1. NUlllber Vaccinated:
Injection No .
Vaccine _1_ .L. ..1
Yeast Recombinant 31 31 31
Plasma-Derived 25 25 25
Serologic data at 7-S 110nths are available for 31 .
recipients of the yeast recOfllbinant vaccine and 22
recipients of the plasma-derived vaccine.
At 7-8 1110nths, 100% of recipients of both the
yeast recombinant (31/31) and plasma-derived
(22/22) vaccines seroconverted (S/N ~2.1) and
developed protective levels of antt-HBs (mIU/ml
~10). The GMT for all vaccinees and responders
24731/2
1 /15/86
00322
Study 807
RESULTS (CONT.): (S/N ~2.1 and ~10 rllU/111) was 885.l mIU/ml for
those persons who received the yeast recOlllbinant
vaccine, and 61&4.4 mIU/Ml for those who received
the plasma-derived vaccine.
By 12 1110nths 941 (29/31) of rec1pients of the
yeast rec0fflb1nant and 100% (24/24) of recipients
of the plas1111-der1ved vaccines retained on
ant1-HBs titer of mIU/ml >10. The 6"Ts for all
vaccinees at that tt111e was 112. 4 11IU/ l (yeast
rec0111binent vaccine) end 1029.2 •IU/ml
(plas111-derlved vaccine).
Anti-HBs responses · at through 12 months are
included in Table l.
3. Clinical Re5ults:
Clinical follow-up data are available for 3i
recipients of the yeast recombinant vaccine and 25
recipients of the plas1111-derived vaccine following
each Injection. Clinical co.plaints and 1111xi111111
temperatures reported following each injection are
provided in Tables 2-5. Jn sunnary:
I Frequency by Injection No.

vacc\n. C11nla1 0alllll•lnt 1 2 3
YNSt - Injection site 10(3131) 3(1/31) 7(2/31)
,,...
J19cmbillAllt Systaic
Injection Site
Systalc
16(5/31)
12(3125)
20(5/25)
7(2131)
' (1125)
12(3/25)
10(1131)
8(2/25)
0(0/25)
No serious or a laming adverse reactions

attributable to vaccination have been reported.
PUBLICATIONS: Heijtink RA, Kruining J, Baker M, Schal• SW. JllnUne

response after vaccination with recombinant
hepatitis 8 vaccine as COfllPared to that after
plasma-derived vaccine. Antiviral Res 1985;
Supplement 1:273-9.
He1jt1nk RA, SchalM SW. Anti-HBs/a determination
after hepatitis B vaccination. Submitted for
publication to Lancet.
24731/3
1/15/86
Study 801
lable 1
Antibody Rnponset ""°"'

Initially Seronegative Health care Personnel Following V•cclnAtlon with 10 mcg
Doses of Reall'l>inant Hepatitis 8 Vaccine lot 912/C-11:444 or 20 ..:g Doses of P1a.a-02rived
Hepatitis B Vaccine lot 1510.J al o.
1, and 6 Months in Study 807
y....... . nt Vaccine p1a- ._...rived Vaccine

\ with Allli__..s an t.1U1■11
.
I with Anli~s GMT CllllU/111 J
Tl111e All - ~ All f1Rct11Nfors
(Ronths) SIN~ 2.1 11IU/11l ~ 10 V.:c\nees SIN? 2.1 alU/al ~ 10 S/N ? 2.1 ■Ill/al? 10 Vacclnns SIN? 2.1 allJ/1111 ~ 10
1 19 (6/31) 13 (4/31) 0.1 16.1 36.4 56 (14/25) 44 (11/25) 3.3 21. 4 36.6
2 11 (24131) 39 (12/31) S.3 12.4 44.6 100 (22/22) 11 (11/ZZ) 59.1 59.1 148.0
3 89 (25/28) JI (20/28) 21.5 35.9 60.1 100 (Zl/21) 95 (20/21) 13S.0 135.0 161.9
i 94 (29/31) 84 (26131) 48.4 68.9 94.8 100 (25/25) 100 (25125) 211.9 271.9 271.9
1/8 100 (31/31) 100 (31131) 885.1 885.1 885.1 100 (22/22) 100 (22/22) '164.4 6164.4 6164.4
9 100 (31/31) 100 (31131) 363. 1 363.1 363.1 100 (24124) 100 (24124) 287VI 2899.4 2899.~
12 100 (31/31) 94 (29/31} 112.4 ll2. 4 140.5 100 (24124) 100 (24124) 1029.2 1029.2 1029.2
0
~
24731/5 l;f
l/15116 N
""
--
Table 2
PATIENT COIMT CLINICAL C011PlAINTS
R[COfllIHANT H[PATIT~S 8 VACCINE
ST\IIIT I 0807
ll!UTH£NT I
l01 NUMDlR I CK444
OOS( 1 U t1C9
PATIENT CUSS: HULTN CM!E PER!IONNEL
'
I TOTAL VACCINEES I 31 PATJ[NTSJ - DOSE l I
Il----------------------------------------------------------------------------1
OAYS POST VACCINATION I tlllt18ER
CLINICAL
COHPlAJNTS 1----------------------------------------------------------------------------•
• t I l I 2 I 3 I 4 I 5 I MITH
•cOffl'LAJNTS
••••••••••••••••••••••••••••••••••••••• .. •••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••I••••••••••
I I I • I I I I
REACTION, LOCAL UNJ[CT. smn I 1 • 2 I O I l I ·0 • 0 I I 3
I C J,2)(1 I I 6.5.!I I C o.ou I I 3.tY.J • I 0.0?.J I I 0.0)(1 I I I 9.1Y.J
-----------------------------------1----------1----···---1--·-------•----------l----------l----------1----------I-----------
PAIN I o I 1 • o I o I o I o I • 1
I I ,.Ol!I I I 3.21.l I I 0.0%1 I I ,.01.1 I I O.Ol!I • I O.O;(J I I I J.2Y.I
I I I I I I I •
STIFFtlESS/TIGHTtft'.SS I l I l ·1 0 • l I O I o I • r
I I J.2l0 I t J.tiCI • I 0.0iO I I 3.tlO I I 0.07.J I I 0.01.1 I I I 6.SXI
-----------------------------------1----------t----------1----------1----------t----------1----------t----------•-----------
STSTEttIC • l I 1 I 1 I 1 I I! I l I I 5
I I J,21.1 I I J.l!Y.I I I J.2XI I I J,UO I I 6.SiO I I J,2Y.J I I I 16.lY.I
NNOLE IIOIITIGENfRAL I
C
0
o.o;o l
1
J.2)!:)
I
J.u:1 I
0
t.OY.I I
1
3.21.J I •
0.9)0
3
9. 71.1
FATIGU[/NEAKNUS I 0 l
' • • 1
• 2
O.Ol!I I 3.2%1 I O.OlO I ,.,21 I J.2)0 I 0,01.J 6.SY.I
HtAOACHI! I 0
I.0Y.I t
0
0.0%1 t
1
3.t:iO (
0
O.IY.I I
0
0.01.J I •
o.o;o
1
J,21.I
JNFEC1IOUS 9YNIJRct1E9 I 0 0 0 1 1 0 l
I I o.o:o I O.OY.I I O.Ol!I I 3.2)(1 ( J.2Y. I ( O.OY.J s.2;0
I
INFlUUIZA. HOS
( •
O.OY.I •
O.DY.I I
0
o.o:l!I I 3.UO
l
I
1
J.f)(J I
0
o.o;o
1
J.2T.J
'
llf!IPll!ATOffT
I
0
I.DY.I I
0
1.0%)
0
O.OXI o.ox,• 1
J.2:0 I
l
J.1!7.J
I!
I . 6.SY.I
' '
(
PffARTHGITIS (SORE THROAT I

I
0
0.01.1 I
0
0.01.1 C
0
I.DY.I I
0
0.07.1 • 0.01.1 I
1
J.2l0 f
l
S.2)(1
I '
0
I 0
UPPER IIESPIIIATffllY INFECT., NOS I 0 I D I I 1 0 l \>I
,.o;o I t.o:o I I D.0)O
' t.07.1 • I J.2:0 ( 0.07.1 J.2:Y.I
"'a:,
Table 2 (cont.)
PATIENT COUNT CLINICAL COHPLAIHTS
RECoteINANT HEPATITIS 8 VACCINE
STUDY I G807
TR!Afflt:NT
LOT NUl18tR I CK'l'l'I
DOSE I 10 NCG
PATIENT CLASS : HE AllN CARE P!RSOHHEL
---------------------------------------------------------------------------------------------·
I TOTAL YACCINE!S l Jl PATIENTSI - DOSE l
------------------------------
•
1----------------------------------------------------------------------------I
I l!AYS POST VACCINATION I HUffl[R
1----------------------------------------------------------------------------I
ClINICAl
CDl1PlAJNT9
................................... I
, O I I I I
................................
I I •
I J
,
..•.......
I
I 'I
..........
I
,• 5
.......... I
•
, ,
MITH
ltOttPLAINTS
..........•..........
I I
11'USCUlOSKElErAL I 1 • I • G • O I o I o I I 1
I , 3.21., I , o.a;o I t e.a:o I , o.a:o I , a.o,o I , 0.01.1 I I , J.t::o
I I I I I I I I
BACK PAIH I l I D I D I o I o I o I I 1
I I J.27.> I c o.o;o I , e.GY.1 I , o.a:o I t ,.ox, I I o.o:it , I I , J.z::o
-----------------------------------1----------
PUSONS WITH COMPLAINTS I l Il----------l----------
J I l Il----------l----------l----------•----------1-----------
2 I 2 I 1 I I 7
I l J.t1.) I C 9.71.) • I 3.t'T.I I l 6.51.1 I C ,.s,o I l :5.t:O I I I U.67.1
-----------------------------------1----------l----------l----------1
PERSONS wnN HO cmPLAINTS .I Jo • ze I Jo I ----------l----------l----------1----------I-----------
29 I n I Jo I I u
I I 96.8%1 I I 90.JY.t I c 96.81.t I t n.s:r.> I t 93.s,o I 1 96.e:o I I 1 11.<1::o
-----------------------------------1----------1
PERSONS Mint HO DATA I O I ----------1----------
O I O 1 I ----------1----------1----------•----------1-----------
O I I I O I f t
I c o.ot> I t 0.1,0 I I 0.01., I I o.o,o I I D.07.1 I I t .01.1 I I I o.o;n
0
0
....
IV
V,
Table 2 (cont. )
PATIEKT COUNT CllNICAl C0'1Pl1IKTS
RECOHISI NAHT HEPITI T19 B VACCINE
9TUOY t 0807
TII EATHENT t
LOT HUl18ER t CK444
DOSE t 10 NCC
PATIENT CLASS• HEALTH CARE Prllsot!N! l
I TOTAL VI CCIHEES ( JI PIT I ENT91 - DO!! t I

1I ----------·------·--·----·-··········--·····-----·---··-·········----------
DI Y! POST VACCINATION
I
I NUr18ER
CLINICAL f •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• --·--·········--1 NlTH
COt1PLAINTS I I I 1 I t I J I 4 I I I IC0NPLAIHTS
................................... I,.......... ,•.......... Il••········•········••
I
I••······························•··········
I • I I
RU CTION, LOCAL U HJECT . snu I 1 I t I I • t I O I O • • 1
I c J .2;0 I 1 0. 11., I I o.o;o I c a.ox, I , o.oic, • , 1.07. 1 I I , J ,2;0
····--···············----······-·-·
PAIN
1-···-·-···1
I 1 •
·-······-·•--·-······1······-···1··········1-·--··-·-·•··-··-····•-··--··-···
t . t I t I O I t I • l
I I J .tlC ) I I 0. 17.1 I I lt.01.J • I I.Dl!I I ( 0 , 0l! I I ( D,Dl!I • I I J.21.1
------·--············-·············1······-···1·--····-·-1
STSTEffIC I 1 I l I
--·-·-·---
O
•-------·--•·-·---·---l·------·-·1
• t I O I O I
··-·-·····1
I
···········
2
I ( :s.z;o I ( J .Z,:, I I 0 .0l!I • ( o. t l!I I ( a.or. , I I o.or., I I I 6,5)0
--------------------------------------------------------------------------------
1 I • I •
WHOLE IIOIJY/GEHERAl I l I l I O I O I O I It I I t
I f J.21.1 I ( J.t:o • C 0.01., I C 0.01.1 • I o.o:o • I o.Ol!I I I I 6.5:o
• I • I I • I I
FATIG\Jt/Mf:AKNUS I 1 I 1 I I I t I O • 0 • • !
• c J.2x 1 I , J.2r.1 I c a. ox, I c o.ox1 • c o.or.1 I c o.ox , I I , ,.,in
-··-----------·-----····--·----·---1-··-······1·········-•··········•·-·······-1·-·-·····-1·--····---1
PERSOMS NI TII Cllffl't.l lKTS I t I l I o I t I D I t I
··········1I ··---·-----
2
I C 6.5,0 I f J ,Z:0 I f D.0l!I • C o . t l!I • C 0.07.J • l 0 ,0Y.I I I C 6,51.J
·-------·-----·--------··---·······•···-···--·1·---------1
Prll 90N5 111TH NO C011PU I NT9 I H I JO •
··---·-···•---···-·-·1·-···-····•--·--·-···•··········1
Jl • :n I Jl • J1 I I
···········
2'
• , , :s.57.1 I c 96.a,o I uoo .ou I noo.ox, I noo .o:o I uot.ox, I • , ,:s.5,o
--·-··-·················-··········1
P£1190N9 Htllt NO DITA I
········-·1····---···1·-········1····-··--·1
a I I • I I t I
-···--···-•···-······1------····1
O • I I •
·----------
O
I I t .D7.I I I 0 ,11. J I I D.OY.I I I 1 . 01.1 I I o,o;,:, I I 1 .0:r.1 I I I 0 .01..1
0
Q
""rv
11'
Table 2 (cont.)
PATJtHT tOUff CLINICAL tct1PLAINTS
RECOHllttlANT HEPATITIS 9 VAtttHE
STUDY 0807
TAEATtffHT I
lOT tUIOElf I CICfl~
DOSE U HCCI
I
PATIENT CLASS• HEALTH CARE PEASOtlNEl
• TOTAL VActltl£ES ( 31 PATIEHTSI - DOSE 3 I

1--------------------··-·------···----··--·-··-----·-··-·-··--·----··-·-----1
• OATS POST VACCINATION I NUlfflER
tllNttAl
tOtlPlAitlTS
•--·--·----·--········--·····-··---------·---·-··--·-··----·---···---·······-I
• D • l • I! • 3 I 4 • 5 I
Wint
ICOt1PU1NTS
•••••••~•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••••••••a•••••••••••••••
IIUCTIOH, LOCAL UNJttT. SITU •• l •I l I• l •I I •• O •• I •I •I r
• ( 9.1!7.I I ( 3.l!Y.I • ( ].!1.1 I I o.o:o I I o.o:o • C o.oie, • • I 6.SY.I
----·-·--·--········-···---···-··--1---·-···-·•-········-1·······-·-1··-·····--1-·--·--··-1······--··1-··--·----1----·---·--
PIIIH • o I l I l I o I o I o I I z
I I 0.0)0 I I J.l!Y.I I I J.l!Y.) I I I.DY.I I I I.DY.I I I D.OY.J I I I 6.S:'-1
I I I I I • • I
STIFFNES9-'TIGtlTNHS I l I O I O I I I I I I I I l
I I J.2Y.I I I 1.0Y.J I ( o.o:o I I o.OZl I I O.OY.I I ( O.OY.I I I I '.!l.2Y.I
··-··--·-·····-···-············-···1----··-··-1-····--·--1·····---·-1····-·--··1···-·-····1-·-·-----·1-···-··---1·-·-·------
SYSTE"IC I l • l • t I l I O • 0 I I '.!I
• I J.2)0 I I J.l!XI • I 6.57.1 I ( :,.2:0 I I O.OY.I I I o.o:n I I I 9.7XI
MfOLE 900Tl'Gnt!RAl
• 0
0.0)0 I
l
J.2,0 I
l
J.21.1 (
0
D.OY.I (
0
0.07.1 I •
0,07.1 I
t
6.5Y.I
HUDACH! I
( •
,.o;o (
l
J.tlO (
l
J.ZZJ (
0
0.0)0 I
ID
0.01., (
•
II.DY.I (
I!
6.5Y.I
IJJC:ESTIVf SYSTI!:" I
• I
•
I.OY.I I •
0.07.1 (
l
J.t:o (
1
J.l!Y.I (
0
0,1?.l (
0
D,DY.I (
1
J.z;n
I
lllARRHEA I
I< •
I.OY.I I •
1.0%1 I
I
J.l!Y.I I
1
J.UO (
0
O,IDl!I (
0
I.IY.I I
l
J.l!Y.I
I
NERVOUS 9Y9TE"
• l
J.tY.I ( •. •,x, I
D
11.0:0 (
0
11.0:0 I
ID
O.Ol!J ( •
,.uo (
l
J.2:0
VEATI601DtUttlUS • 1 I I I O I I I o I t I I 1
I f J.tXI I ( 0.0%1 I ( I.DY.I I C o.o:o • I o.o:'.I I ( ,.o?.I I I (, J.l!Y.I
·······-····-··--··-·-··--·---·····1·-·-·····-1·--·-·-···1···--··-··1···-······1-·········1·--·-·--··•·--·-···-·1···········
PEIISOHS MITH COtlt'LAIHT9 I t • t I J I l I I I O I • 5
• I 6.5l!I I I 6.5)0 I I ,.1;,:1 I C J.2;0 I f o.o:n • I o.o;o I I C 16.11.1 0
--······-·-···-----·--·---····-·--·1·····--·-·1-···--····1······-··-1·-·--··-·-1········-·•-·--····-·1-·---·····•····---··-·
PElf!IOHS NlTH tlO tOf1PLAtHTS I H I t• • ts I ,. I ll I 31 I • t6
0
\,4
I I 9l.5l0 I f '3.5%1 • I 90.J~I I I 96.eY.I • 1100.07.1 I UOD.01.1 I I I 81.91.J N
.....
Table 2 (c-ont.)
PATllHT COUNT CltHtCAl Cot1PlAlffTS
REtOt191HANT HEPATITIS 9 VACCINE
STUIJ T I 0807
TRUfflENT
lOT tlUll8fll' CK444
DOSE I lD ffl:G
PATl!Kt CLASS: HE ALTH CARE PfRSIINNEl
I TOTAl VACCINE£! C JI PATI ENT91 - DOSE J I

•----------------------------------------------------------------------------0
• OATS POST VACCINATIOtl I HUl18ER
ClIHtCA l •·••-------••·-··•--·••••••··••·-·······--------·-------------····-----··-·- • NJTH
CONPLAiflT9 I O • I • t I J I 4 I 5 • ICONPUINTS
••••••••••••••••••••••••••••••••-• l••••••••••l•••••••••••••••••••••l••••••••••••••••••••• l••••••••••l••••••••••I••••••••••
-----------------------------------
Pttl SOH, eintt "° DATA
•----------•----------1----------1
I • I • I • I----------1----------•----------•----------
• I o I • I •-----------
II I O.D?.I
•
I c t .01. 1 I t t .OXI I I o.o;o I t 1 .0?.1 I t o.o,o I I 0 . 11. 1 I
0
0
1,,-1
N
0D
Table 3
PATIEN1' COUNT NAKI..-, TEHPEIIA'YUIIE!I
lllCOt19lHAMT HEPAlll,lS II VAttIHf
STUDY I 0807
TIIUTl1ENT
LOf NU18ER : OC444
DOSE : I O HCC
PATI ENT CLA!l!II HEAllM CARE Plll!IOtML
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINtES C 31 PATl [ Nf!II • DOSE 1 I
•·······································-······--··--···-·-----·--··-·-····---------·-·-
I DAYS POST VACCI NATION
1I Hln!II
tlAK TEKPERATURE
CDEC F , OIIAll
1•·-·-·--•--··•••-·-··-···••··•••··--···•-•···••····-········---·--·-··-···-·---·-·-····1
I I I 1 I 2 I l t '- t S I I
MITH
I HAK TUff'
••••••••••••••••••••••••l••n•••••• •••••••••• •••••••••• •••••••••• ••••••••••!•••••••••• ••••••••••l•••••••••• l••••••••a•
I I I
HORIIAL I 1 1 1 1 l I I I l
I C J .61.) C :J.T/. ) C J .T/. J I :J.T/. 1 C J .T.1.1 I C J . 1:0 I C J .t:o
I t I
< 99 I U rt U 25 Z4 I Zit I U
I I 1 2,ll!I C n.si!J C es.uo I 92.6'0 I 89 .91.1 I C 92.JY.l I f 67 . 71.1
I I I
,, • 99., I 4 J J o o I l I 6
I I 14.JlO I Jl .17. J l 11 , l lC I I l , Oi! I I l , Di!I I I J.81.1 f I 1'. 4i!I
I I I
I OI - 100. , I o l O o 1 I O I Z
I I 0 ,0)0 I J. TX I C o.o;o I 0. 111. 1 1 :J . 7i'.) I I 0 .01.) I C 6.s:o
I I I
lH • 101 . , I o o o 1 1 I o I 1
I l 0 . 01., C 0 .01. 1 l o .or.1 ( J ,T/. 1 I J, 71.1 I C 1 ,07.l I C J.z;o
---···-···-·-·-···-·-···1·-·-·---·-1·-···-····1
nNPHATimE TAKEN I H I n I
···-······1-·····-·-·1-··-·-···-1
21 I 21 I 21 I
·····-·--·1
26 I
-·-·····-·········-··1·-·········
I n
I I to . J 1. I I I 8 7,U!I I I 8 7.llO I I 8 7. Ul l I I 87 ,llO I t &J .97.1 I I 1100.01.1
······--··-·············1·······•-•l--·-······1
lfflPtRATURE NOT TAKEN I :J I 4 I
····-·····1·····-·-··1-·---·····1
4 I 4 I 4 I
··········1
9 I
·-··················1·-·········
I 0
I I , . 7l'. I I t 11! .91.J I I U ,9lCI I I U.91. 1 I I U ,9XI I C 16, l Y.l I I I o.o;o
Q
0
~
rv
,0
Table 3 (cont.)
PATIENT COUNT IIAX111U11 TEtff'ERATUsrES
RECottBINAHT HEPATITIS 8 VlCCINt
STUDY l CIII07
TREATtttNT I
lOT IAJll9[R I CK<\44
DOSt : 10 tlC~
PATIENT ClASS: HEALTH CAR! PERSOf!HEL
I TOTAL VACCINtE9 I Jl PATIENTSI - DOSE 2 I

1---------------------------------------------------------------------------------------•
• DAYS l'OST VACCINATION • Nllffl!ER
NAX
IIIEGttHl't:RATURE
F. MAU •
I
O •
•
l !
I
• J
I
I 4
•
• 9
I
,
•-------------------------------------------------------------•-------------------------•
I •
•
•
,
• flAXMITH
....................................................,. ....•..........•...•...... ................................. ..........
•
TEIIP
<9' I u • ttt • ts I n I u • u • I to
• c 1a.6lO I c as. r1.1 I , 96.2,0 I , u.a:r., I , .s.aio I 1100.oio I • ,. 11.,r.1
I I I I • I I •
99 - 99.9 • s I 4 I o I 1 I 1 I • I • 7
I , 11.,:r., I , 1,.11., I , o.o;o I , •.tin I , •.uo • , o.oio • I I u.or.1
I I • I I • • I
I I o I o I t I o I I
100 - 1110. 9 1
t , J.61.I I c ,.o:r.1
1 •
I I s.ar., I c o.or.1 I c 0.0:r.1 I , 0.0:r.1 I • c ,.,1.,
1
-----------------------•----------•----------•----------•----------•----------1----------1---------------------•-----------
lEIWEIIATURE TAKEN • ea • 211 1 2' 1 2' I '" I n I I 20
I r 90.JY.I I I 90.Jl!I I ( eJ.9l!I I l 11.•1.1 I c 11.«1:o I I 1•.2:r.1 I I I 91.J?.l
-----------------------l----------1----------1----------l----------l----------l----------l---------------------•-----------
n""t1tAnJ111E NOT TM.EN I J • J I s I 1 • 1 • • I I J
• 1 ,.no • c ,.1x1 I , 16.t:r.l • c u.,in • , u.,:r., • c es.e:r., I I , ,.n1
........
0
0
Table 3 (cont.)
PATIENT COUNT 11AXIt1Utt TEl1P£RATURES
RECClt111IHANT HEPATITIS 8 VACCINE
!TU!JT I 0817
TRUTMNT
lOT NUteER CK44•
D0!11: I 10 HC8
PATll:NT ClAS!I HfAllll CAR! PfR!HlNNEl
I TOTAL VACCINUS t Jl PATIENTS I - DOSE J I

l---------------------------------------------------------------------------------------1
f DAYS POST VACC1"ATIOM I HUt18ER
nax TEnPERATUAE
I DEG F, ORA Lt
1--------------------------------------------------------------------------------------I
I O I I I ! I J I 4 I 5 I I I ff Al(Wint
TEHP
nn••••••••••••••••••••l••••••••••I•••••••••• •••••••••• •••.. ••••• •••••••••• ••••••••••l•••-•••••l••••••••••l•••••••a••
I I I I
NORMAL I 5 I 5 s s S s I I s
19.ZXJ I t 1'.27.J I 19.21.1 I 19.ZY.I I H.01.I I 19.!i'.I I I I 18.SY.I
I I I
< ,, I 17 I to 17 19 19 1, I I 111
65.47.J I I 76.97.t I 65 ••,o C 73.1>:t I 76.,:o C 7J.11.I I I I 66,77.1
I I I
99 - 99, 9 I 4 I l • l l ! I I J
, 11.•1.• I , s.11r.1 , n.•r.• , J.BY.I c •.1i1 , 1.n, I I • 11.1:0
I I I
llDt - 100.9 I O l Cl O 1 I I I I 1
I , 0.01.1 I , o.o;r.1 , 1.01.1 I , J.117.1 I t o.o;o I , o.o,o I I , ,.r1.1
------------------------1----------l----------l----------l---··-----l----------l----·-----I---------------------I-----------
TEHl'rRAT\Jltl! TAKEN I H I H I !6 I t6 I !!J I 26 I I Z7
I I " · ' " ' I I 8J.9:'.I I I SJ.9JO I I 8J.9XI f I 80.6%1 I I SJ.9)0 I I I 87.llO
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEffl'EIIUURIE NOT TAKEN I S I 5 I s I s I 6 I s I I "
I I 16.1x, I I 1'.llCI I I 16.UO I I 16.UI I I H.4:!I I I 16.Un I I I l!,9,0
0
0
""....
1,,1
Table 4
PATIENT COUNT CLINICAL COl1PLAINT9
PLAS11A-OEAIVEO HEPAl~TIS B VACCINt
STUOT D8D7
TR[ATI1ENT
LOT NUHBCII lSIDJ
I
DOSE l!O ttCG
PATU.NT CLASS: tlEALTlt t._l! fltll90HHU
• TOTAL VACCINE£5 ( 25 PATIENTSI - DOSE l •

•------------·---------·---·-·-------·---·-·----·-·--------·-·----·-·--·---·-•
• DAYS POST VACCINATION • t«JMBER
CLINICAL •···-----··----------·-·-·-·-··----·-·-----•---···•·------••••··•······-·-·-· • NJTH
cottPLAINT9 I D I 1 • z I J I " I s I l cot1PLA1Mn
••••••••••
0
••••••••••••••••••••••••1••••••••••1•••••••••• ••••••••••••••••••••••1••••••••••1•••••••••••••••••••••1•••••••~••
I I I • I I • •
RUCTION, LOCAL CINJECT. 9lTEI • J I l • I • l • I • I • • J
I l U.01.1 I l 4.0Y.I I C 4.0Y.I I I ft.DY.I I I 4.0Y.l I I •• DY.I I I I lt.Dl!l
-···---·---·-·-------------·----·-·1-----·----1---·------•--·-·--···1----··----•·-··-··--·•·····-----•-·-·····--1--·-·---·--
pA 1N I z I 1 I 1 I 1 I 1 I 1 • • e
• C e.0XI I f 4.0l!I • I 4.0lO I I 'r .DlO • I 4.D)!I I I 4 .0XJ • • ( e.o;o
I I I I I • • I
STJFFNU!I/TICHTNH9 I I I O I O • o • o I o • • 1
I I ,.oz, I C o.o;o I C 0.07.1 J I 0.0lO • I O.0l!I I ( I.OZI I • ( 4.0lO
-·-·-·--- ·-·-·-·-·-·-·-·····-··----1-·-··---·-1····-·-·--1-·-··--···1-·--··---·•--·-··----•·--··-·---1-------•--l-•---------
!nsnn1c • 1 • J I 1 I 1 • o I • • I s
· • I 4.0ZI • C 12.0Y.) I C ,.o:n I I 4 .0Y.I I I 1.07.) I I o.o:o I • I 20.07.J
l!IIOLI! l!OOYIG(N!AAL
• l I 0
•
0. DY.I I
0
a.ox,
0
O.0l!t
J
U.DlO
FATIGUE/14EAICN£SS
11 .01.1
D
C 8.0XJ
1
I O.OXI
0
C
0 ., ' ., l
• o.ox, o.oxt t .11. t 4.DY.t
' 4 .01.t I
.,
C I.DY.I
' 0.0%1
'
Ill.NHS , NOS I l
•.o:n
l
o.oz,
D II
I • z
11.0:n
I 4.r.1.1 I
' O.OY.I I O.0XI 0 .0:r.1
IIU!ICULOSKtlETAL I D
o.o:o
l
'r.a;o •
o.o:o •
1.1?.I I
D
1.0?.t • 0.01.t
1
... ,u
' ' ' • C
•
BACI( PAltC
• 0
,.o:o I
1
4.DY.J (
0
D.OY.J I •.,x, I
0
0.0Y.J ( O.OXI
l ·
4.0Y.I
DI&ESTIVI STSTEH
• 0
0.0:r.1 I
1
4 .01.t I
1
4.07.1 I
I
4.0l!I I
0
0.0,0 (
0
0.0Y.I '
I . 11.0:0
DUrnlHEA I
•
O.Ol!I I
l
4.0iO
l
C 'r.Ol!I I
l
11.0l!I C
0
o.o,o I
0
0.0l!I I
r
8.0::0 0
0
vonnmu I 0 0 0 l
o.o:o C "
O.0Y.J l
0
O.tY.l I
J
4.01.) I 0.01.) C 0.0Y.I I 4.01.J
~
uf
N
Table 4 (cont.)
PATIENT COUNT CLINICAL COfflllAINTS
PlAsttA·DERJVEO HtPAJITIS 8 VACCINE
STUDY I 0807
TI! EA TttUIT
LOT tuflefl' t l !llllJ
DOSE to t1CII
PATIUIT CLA!l!lt HE ALTH CARt l'tR!IONNE l
• TOTAL YACCINEt!I ( t!I PATJ t HT!II - DOSE l I

1----------------------------------------------------------------------------I
• DAT!I POST VACCINATION • NUffllEIII
CLINICAL
COttPlll IHT9
1
•
-------------------------·-·-···-·-·---•·•••------•------•-------·--------·-•
o • 1 I z I J I ,. I , I
WITH
•conPLA IHTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••• ••••••••••••••••••••••••••••••••••••••••••••!•••••••••••••••••••••
-----------------------------------•----------1----------J----------•----------•----------•----------1----------1
PERSONS MI TH COHPLAINT9 • • • It I I I 2 • 1 I l I •
-----------
7
I I 16.IIY. I I I U, .OY.I I I 8.0l!I I I 8 .0l!l I I lt.OlO I ( •. Ill!) I • I 28.0lO
-----------------------------------
P£11SOMS &lllN NO COffl>LAlNTS
t----------1
I U I
----------
U
l----------1----------I----------I----------I----------
I U I U • Zit I Zit I
I-----------
I 18
I , e • .11io I I e to.cr,o I 1 ,z.ol!I I 1 ,t . o:r.1 I 1 96.0l!I I c '6 .111.1 I I « n.o;o
--------·--------------------------l----------l----------1
P£RSON9 MITH HO OAlA I t I t I
----------1------·---•----------l----------1------·---1
O • 0 I II I I I I
-----------
o
I t 1 .ol'.1 I t 0.01.1 t t o.o;o I t o.o:o I t 11.01., • 1 o.oY. , I I c 1 .oY.1
0
0
u,I
.....,
.....,
Table 4 (cont.)
PATlEHT COUNT CLINICAL CottPLAIHTS
PlA5ttA-DEAivtO HEPAT~TIS 8 VACCINE
STUDT 0817
TREATHtffT
LOT NUttB[A I 1910J
DOS£ I 20 ttCI
PATIENT CLASS: HEALTH CARE PER!ll»IM(L
I TOTAL VACCINEES I 2S PATI[NTSI - DOSE Z I

•----------------------------------------------------------------------------1
I DAYS P09T VlCCJNlTIIJN • NUHBEA
1----------------------------------------------------------------------------I
CLINICAL
Cllffl!LAIN'9
...•...................•.....••.••. I
, O • 1
.....................
I I
•
•
2
,
.......... I 3
..........
I
,
I 4 I
,I
......................
I
I
•
NitH
ICottPLAJNTS
..........••......... ,
I I
AUCTIOtf, LOCAL tJNJECT. snt, I 1 I t I a I o • o I • I I 1
I c 4.ox, I 1 0.01.1 I 1 0.01.1 I , 0.0,:1 • c o.oY.> I I o.o;o I • 1 4.o:o
-----------------------------------•----------1----------1----------l----------l---·--·-·-1----------1---·------1------··---
PAIH I 1 I O I O I O I D I t . I 1
I I 4,07.t I 1 ,.o;o I 1 0.07.1 I 1 0,OlO I C ,.o:r.t I I 0.0:r.1 I I .I 4.0l!I
-----------------------------------•----------1----------l----------l----------l---·------l----··----I----------I-----------
SYsn:tt1c I l I Z I I I o I 1 I o I I J
I I U.07.t • I e.o:r.1 I 1 fl.0lO I I 0.07.t I I 4.0lO I I I.DY.I I I I 12.0Y.I
-------------------------------------------------------·---------------------------------------------------------·----------
I
NltOlE BOOY/GENERAL I t 0 0 0 I J
'
u.o:r.1 I e.o:io (
1
4.0XJ ( 0.07.I ( •• 07.J ( t.07.1 I c u.a;o
I
FATIGtJE/1,!fAKMHS I J z 1 0 a 0 I J
u.o:o • 8.tlO ( 4.07.1 1 0.01.1 I a.ox, ( t.0)(1 I 1 12.07.I
I
ULNt:SS, NOS I 1 0 0 0 D 0 I 1
4.0%1 1 0.0lO I O.0l!I ( 1.07.1 ( D,Dl!I ( t.0)O I • 'b.o;o
I
tlUSCULOS!';£lUAl I 0
o.o:o I
1
4,llO I
0
0.0)0 (
0
0.07.1 (
0
0.0)!1 C •
0,0,O
I
I I
1
4,117.1
I
IIACII: PAIN I 0
a.o:o I
1
4.0)0 I
0
t.01., I
0
0.01.J (
II
0 .01.I I
0
t.o:o '
• I
1
4.0XJ
DIGnnvt SYSTffl I 0
1.0,0
• •.",x, I
0
0.01.1
•
0
0.07.1 I
1
"•0lO 1 •
t.o::o I
1
4.0:0
STCl1ATI TIS I •
o.or., C
•
0.OiCI C
•
o.o;o I •
0.07.1 1
1
-.07.1 I
0
0.11;,:J
l
, . ~.ox,
I
lltAYOUS STSnn I l 0 I 0 0 a 0 l
4.o;o I 1.ox1 I 1 O'.OiO C D.07.1 I O.OiO 1 0.0>:I C fl.01.1
0
I 0
VERTtGO.IDIZZIN£S9 1 0 I 0 0 0 0 1
•I 4.0l!J a.ox, I , t.o:io a.ax, t o.o;o I 0,0%1 I fl.O:f.l ....""
C
' "'
Table 4 (cont.)
PATIENT COUNT CLINICI L COffl'LI INl'S
Pll stlA-DERIVfD HEPAJ I TIS 8 VACCINE
Sl\JDY I D8t7
TREATNEHT t
LOT NUt18ER t 1510J
DOSE I 20 NCG
PATIENT Cll SSt HE ALTH CARE PERSOM«l
I TOTAL VACClNlES I 25 PI TIENTS I - DOSE ! I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I MU11BfR
CLI NICAL
COl1PLAIHTS
l----------------------------------------------------------------------------1
I O I 1 I t I J I 4 I 5 I
WITH
ICONPlA INT9
•••••••••••••••••••••••••••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
-----------------------------------l----------1----------
PEll90NS WITH COt1PlAJNTS I 4 I 2
l----------1----------1----------1----------I----------
I 1 I o I l I o I I-----------
I "
I c 16.or.1 I c a.o:o I 1 • .o:o I , 1.or.1 I c 4.oz, I , o.o:o I I I u.1z1
-----------------------------------1----------l----------l----------l----------1----------l----------1
PER!OffS Ni m NO C0f1PUJNT9 I ti I U I 24 I 25 I 24 I H I
----------I-----------
I 21
I I IJ♦ .07.I I I •2.e,o I C ... 07.I I 1100.0iO I I 96.07.1 I U 00 . 07.1 I I I 84.o:o
-----------------------------------1···-------l----------l---------l----------1----------1----------1----------I-----------
PHSOtlS MITH NO DITA I O I O I O I O I O I O I I O
I I o.or. , I I D.07.1 I ( o.o:o I I 1 ,07.1 I I o.or.1 I I 1 .07.1 I I I 1.0:0
0
0
l.,of
""
V,
Table 4 (cont.)
PATl[NT COUNT CLINICAL COHPLAINT5
PLASNA-DtllIVED HEPAT~TI9 B VACCIHE
sn.11n· I 0807
TIIUTHtNT
LOT Nlffltll lSUJ
bO!( 20 HCG
l'ATUNT CLA!l!I: HEALTH CARE PEll!IOMNll
I TOTAL VACCIN£!9 ( 25 PATl[NTSJ - DOSE J I

•----------------------------------------------------------------------------1
• DAYS POST VACCINATION • HUHBE:R
CLINICAL
COffl'UtNTS
•-----•-------•---------------------•-•---•--•-------------------------------1
• t . 1 • 2 I J • 4 I 5 I WITH
•cOHPLAINT9
oo•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
I I • • I I I •
IIEACTION, LOCAL UNJ[CT. SITU • t • 0 • 0 • 0 • O • 0 I I t
• I e.o:o I I 0.01.1 I I 0. 01., I I 0.01., I I 11.01.1 • I •• ,1.1 • • I 8.0:1!1
-----------------------------------t----------•----------l----------•----------•----------1
PAIN • t • 0 • 0 • I I O • ----------1----------1-----------
0 I I t
I C a.ox, I C o.o;o I ( o.o:o • I o.o;n • I O.OY.I I ( 0 .01. 1 I • I 11.0:0
-----------------------------------•----------1----------•----------•----------t----------l----------•----------l-----------
"ERso11, MITH COl1PLAINTS I ! I I I O I O I O • . t I • t
I t 8.DY.J I I 0.07.J I I 0.07.J I l t .OY.J I I o,oin I C 0.01.1 I I I a.or.I
-----------------------------------
,E:11sOHS w11N HO cOHPUINTs Il----------l----------t----------1
rs I ts I ts I ----------l----------l---------l----------l-----------
ts I t5 • rs I I 21
I I ,2.01., I 1100.01.1 • 1100.01.1 I 1101.07.1 • 1100.01.1 I 1100.0;0 I • c '12 . 0Y.J
-----------------------------------1----------•----------1----------1
P£1190ff9 lltffl NO DATA I I I O I O I ----------1----------1---------•----------1-----------
I I I • t I I 0
I t t,OY.I I ( O.l",',J I C 0.01.1 I I 0.07.1 I t o.ox1 I I o.07.1 • I t 0.01.I
0
0
""
""
"'
Table 5
PATIENT COUNT HAXll1Ul1 TEl1PERATURES
PLA5NA-D[RIVED HEPA~ITIS 8 VACCIHE
STWY I 01107
TRU THENT l
LDT HUtlB[R 15U J
DOSE 20 NCO
PATIENT CLASS: HE ALTH CARE PERSONNEL
I TOTAL YACCltllES ( ZS PATIENTSJ - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DAYS POST YACClHATlON I NIR'l8ER
NAX TEffl'fRAT\JRE
tDEG F , ORALJ
l----------------------••--•-•···•------------------------------------------------------1
I O I 1 I I! I 3 I 4 I 5 I I I "AXMITH
TEHP
a••••••••••••••••••••••• l••••••••••l••••••••••I••••••••••
I
•••••••••• ••••••••••••••••••••••••••••••I••••••••••••••••••••
< n I 19 I te I 20 16 1 11 zo 14
I , 111.sr.1 I
112 . 6l?J c 81.01. , 1 eo.01.1 1 ei.8lO 1 ,s.z;o 1 58.s:o
I I
,, - 99 .9 I 3 I s I 3 4 J o 7
n.o;o I I n. no I I n.or. , ( zo .oio I U .f>)(I I O.OlO I 29. ZY.I
I I
110 - 100. 9 I o I o I t o 1 o l
o.o:o I I 1. 07.J I C o.o,o I , .o;o C It . SY.I C , .or., I 4 .27.J
.1 I
101 - 101. 9 I o I o I o o o 1 1
0.01.1 I c ,. o?.1 I I o.ox, , o.o:o • o.o;o , 4 .87.1 1 4 .21.1
I I
lDZ - 1oz. 9 I l I o I o t o o 1
I C 4 .J1.I I C 11 . 11.1 I I o.o,o ( o.o:o I I o.or., I I o.o::o C 4 .t?.I
------------------------l----------1
TAKEN
n 11PEIIATURE I ZJ I
----------l----------l----------1----------1----------l---------------------
tJ I U I 20 I U I U I
l-----------
I !4
I I 92. 07.J I C 9Z.07.I I I ,z.oio I I 80.0)0 I I 118.0)(1 I I 84 .o:o I I I w..or.,
------------------------1----------1
TEHPERATUIIE HOT TAKl!N I t I
----------l----------l----------1----------I----------I---------------------
Z I Z I 5 I 3 I • I
I-----------
I 1
I l a .ou I C 11,0lO I I e.ox, I I to.ox, I I u.o;o I C 16.07. ) I I t 4 .0)0
0
,.,.,
0
""'
--.!
Table 5 (a,nt .)
PlTilMT COi.ACT NlKI ~ Tlffl'ERAl\Jll(S
Pll5"l-O(RIVED HEPA~I TIS B VACCINE
ST\IOY : 0907
TIIEAM NT 1
LOT MU1BER : 1519J
DOSE I 20 IICG
PATIENT CLASS: HEALTH CARE PfRSON«L
I TOTAL VACCIME£S C ts PATUHTS I - llOSE t I

1I ---------------------------------------------------------------------------------------
DAYS POST VACCINATION II HJn'BER
l--------------------------------------------------------------------------------------1
nAX TEnP(RATURE
I DEG f , ORALt
........................,
I
I O I 1 I t I J I ~ I 5 I
, I
WITH
I nA>< TEltP
........................................ ......................................... ..........
I
,
I
HOR"AL I 5 5 5 5 I 5 5 I 5
n.Tl. t C t 0. 87.1 I ro.e;o C tJ.&Y. I I C tl.7i0 C tz.n, I C 20. e;o
I I
<tt I " u u U I U " I U
H .67.t c 1O.e,o , 10.e;o c 71,410 I , n.,;o c 12.no I I H.r1. ,
I I
ff - "· ' I 2 t l lI l 1 I t
8 .7Y.t I 8 .JY. I C 4 ,17.1 C 4 , 8 :0 I C 4 .:,;o C 4 ,SY.I I I 8 , :SY. J
I I
101 - 101. 9 I o o l o • 0 O I l
I , o .OY. t I , o .oY.1 1 4 .2Y.I • 1 o. ox, I , o.oY. , I c o.o:o I I , 4 .tY.I
------------------------1----------1
TEnPlRATURr TAKEN I tJ I ----------l----------•----------
z, I z• I fl I1----------1----------•---------------------I-----------
U I U I I t4
I c ,z.01. , I c %.or. 1 I c .._ ,oY.1 I, 94,07. 1 I 1 •z.oY.1 I, es .ox, • I 1 96.01. 1
------------------------1----------1
TIEHPIERAT\JIU HOT TAKEN I t I ----------•----------•----------•----------1----------1
l I 1 I 4 I t I 3 I ---------------------1-----------
I 1
I I 8, 07. 1 I I 4 .D1. I I I 4 .0Y.I I C 16,0)0 I I e.r,o I I u .o;o I I I 4 .0i! J
0
0
V,
\,l
OD
Table S (C'Ollt.)
PATIENT COUNT NAXIl1Ul1 TEHPERATURES
PlASHA-DERlvtO HEPATITIS B VACCINE
STUDY : 0807
TREATHl:NT 1
LOT NIRfflER I 1510J
DOSE I U HCi;
PATl £NT CLASS: HEALTH CAR! PERSotfiEl
I TOTAL VACCI IIEES C 25 PAT IENTSI - DOSE J •

Il---·-·-·-···--···--····-·----·-·-----·-----------------··----------··-····-------------1
DAYS P0!5T VACCINATION • NUHl!ER
NAX TEftPER ATUIIE
I DEG f, ORAL I
1-------------------·-·-------··-----------------------·---·•------·-·---·--------··-•·••
I O I 1 I t I J • fl • 5 I I I
WITH
HA)( TEMP
o•••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••I••••••••••••••••••••••••••••••••••••••••••••••••••••••
•
HORHAL I 10 II 10 I• 10 II 10 II 10 •I 10 •• I
I 10
• I 11 7.61.1 I C 4 5 .SlO I C 45.57. 1 • ( 115.SiO I l tis.s;o I I fl7.6i0 I • C 45.SXI
I I I I I I I I
< ,, I , I 11 I 11 • 12 I 10 I 11 I I 10
I I tit .91.1 I C !IO.Ol( I I I 45.57. 1 I C 54.510 I I 45.SlO I I 5 2.itlO I I I 45.Sl!I
• I I I I I I I
n - " ·' I t I 1 • 2 I o I t I o I
I I , .s;o I C 111 .SX I I C , .1:r. 1 • C 1 .01.l I I 9. l l(I • C I .OY.I •
I t
• I 9.ll(J
------------------------•------·-·-•··--·-----1
TENPERATURE TAKEN I n I zt I t2 I 22 I 22 I 21 I-···------l-·--·-·-·· •······----1---·-·····•·-··-······-·---·---·1-·-··---··-
I 22
I C &ti.OU I C M .07.1 I C 98 . I XI I l 1111.0".l.l I I M. o;o I I 8 fl.OXI I I C 811.0l(J
------·--··--·-------·-·1I --------·-1-·--··--·-1
TEflPERATU!IE NOT TAll:IM 4 I · J •
·---······1······--·-l---··-----1
3 • J I 3 •
··-·-·····•·······-····-·---···-•··-------··
4 • I 3
I C 16.01. 1 I C l t.01.l I I lt. l lO I C U .OY. I I C lt.07.l • I 16 .01.1 • • C lZ.Ol!I
0
0
"'
1.,-f
,0
003QO
A111Mral Rutarch. Suppl. I (198S) 273-279

Proc. h1 ln1. Ti-:O Con(. Antivinl Res. 19SS Rouerdam
A. Billi2·u. E. 0c Ocrcq ~nd H. Schcllckcns (eds.)
e 1985 El,cvicr Science Publishcn B.V. (Biomedical Di,-i1ion)
Ht·I\JttE 'RESPONSE AF'TER VACtlNi\TIO~l WITH P.ECO."\SINA!'ff HEPATITIS 8 VACCIHE AS

co:◄PAP.EO TO THAT A.-""TER PLASHA·DERIVED VACCINE
R.A.MtIJTH:K, J.KRUININI., H.BAMR·, S.11.SCHALHtt

Deoertfflents of Virology end Internal l'.edicine, Eruaus Unive,:-sity Rotterdam,
~otterda:, The Netherlands
SU!«"~Y
Thirt1-one individuals {health can workers) were v1cctnated with recllllt>i-
nent he~!titis B veccir.e (10 ~9 dose) and their i11DUne response (antf-Hlls)
was co=iptred to th!t of twenty•five hulth c1re wort.l!n after vacc-ination
with pl1sma-derived vaccine (20 ~g dose). An:hough the.seroc:onverslon rate
and the percentage of anti•HBs/a antibodies•~ 110nth 7 were c0111p1rable, the
geometric 11ean titre of antf-HBs at 110nth 7 was considerably lower for the
recombinant . vaccine group (857.4 vs. 6736.5 IU/1). However, vaccinees from
the two groups showing seroconversfon at 110nth 1 hid COllll)&rable titres at ·
lllOt\th 7. Raising the dose ~f HBsAg in the rec0111binant vaccine may favour~bly
influence the seroconversion rate at 110nth 1 and thereby the i111111ne response
1fter three injections.
IHTROCUCTIO.'t
Only six years ago, 1 pl1s11&·derived vaccine was introduced to overaae
the world,,tide problem of hep1titls a fnfections. 1 General 1ccept1nce of the
vaccine, ho'..-ever, has been h11111ered by the hfgh costs and in p1rticul1r by
dou~ts 1bout the suitlbility of infectious pl1S111 as its source. Public
concern has wan~ considerably since the disco~ery of hiaan T•cell leubeaia
virus as I possible cause of the acquired i1111111ne deficiency syndn1112 end the
possibility of investigating the effic1cy of inactivetion of this -rirvs 1n
vaccine preparation procedures. 1 Meanwhile, an 1ltem1tfve for the latter
objective his been found in the prepar1tion of hepatitis B surface antigen
by recoabinant OKA t1chnoloqy· in the yust Sao~n• arwi.ia. 1
AHhough the yeut recombfunt DNA produced HBsAg polypeptides, unlike the
nat~ve HBsAg. are not ·glycosyhted, the vaccine thus prepared has prove_n to
induce protective antibodies during chillll)1nzee challenge studies.• Its
safety 1nd 1municity in Nn has been detlonstrated by several groups of
investigators.' • ' • _One of these studies 1s presented here. ,
273
0034i
Soon after the introduction of the plasma-derived vaccine it was uncertain

whether an HBsA9/1dw vaccine would protect i91inst HBsAg/ay,, virus infections.
llowadays it is generally known fron chic:panzee studies u well es experii;ients
In m,n 1 1 "_ that the antibodies dirtc:ed agtinst the 111ain deter111inant !.
provide cross pr-otec:tion for infections with strains not incorporated in the
nccine.
However; in the :,luma-derivtd vaccine studits 11 1Z it was found that the rela-
tive pro:,ortion of anti-KBs 1ntibodies is varilole, which uy partially account
for hepatitis B infections fo the first few 110nths 1fter vaccination. There-
fore, the need to mn1tor the developr.:ent _of anti-t!Ss/a utibod,es after
vaccinition 1s str1ssed.
tlATERIJJ. A.'iO NETIIOOS

Pc:ouhticiri
The study population con,isted of 56 health a" workers. Rec:011bi111nt
ncc:fne wu given to 31 individuals (17 f'ema.le, 14 ule; ••n age 32 !.
2 yr, r1nge 20-59); plama•derived vaccine was given to 25 individuals
(13 ·feuh, 12 1111le; 11ean age 30 !. Z yr, range 22·53). Plr-ticipants to this
study were ne91tiv1 for· HBsAg, anti•HBc, and antf-HSs 1nd had a nonial
alanine transferase level 1t the entr1nce to the study.
V1cctne
Par-ticfpants were nc:cln•ted at O, 1, ·• nc1 6 110nths with either • 10 "9
HBsA9/1dw dost of the recOlllbinant hepatitis 8 vaccine (Herek, Sharp and
Oohme, lot 972/C-K4•4) or a ZO u9 H8sA9/adw dose of the plasm-derived
. v1ccine (Herek, Sharp and Oohme, lot 1510 J). RecC1111bin1nt H8sAg used here
1
w1s purified by hydrophobic interaction
.
thl"Olllltogr1phy.
.
'
AsHys
HBsAg, 1nti-H8c, anti-KBs were 111t1sured in c011111erci1lly available kits
(Ausri1 II, Corab, and Ausab; Abbott Laboratories, Horth Chic:190, USA).
The concentration of anti-HBs was calcul ated by the 11ethod of Hollinger
et al. 1 , and expressed in IU/1 after c011p1rison with the WHO standard pre-
p1r1tion (125 IU/1), obufned fr1111 _the Central Laboratory of the Netherl1nds
Red Cross Blood Transfusion Service, Alasterd•, The Netherlands. Cllculations
were 111de for positive results in Ausab only (sample/negative control ratio .
.?_ 2.1). Samples containing 110re thin 200 IU/1 were diluted and retested.
Dilutions were 11ade in the negative control sel"IIIII fn1111 AuJ1b. Esti11&tion of
the proportion of 1ntf-H8s/1 •ntibodies was perfonaed according to the
.-e thod of Hoofnagle et 11. 1 ' In short, undiluted or diluted ser1 conta~ning
1000-zooo tptn In Ausab ttere Incubated for 2 h at rooca tet1ptr11ture with
pooltd K8sAg/ ad , H81A9'ay, i nd nol'lllal hUlllln ~•rum. respectively. Poaled sera
00342
included reference sera from Or .A.M.Cour-ouce-~&uty u mentioned in in urlier

stu~y. 11 Reduction of cpm after incub1tion with nBsAg/ay strains me~sured
the anti-HBs/1 pr-oportion of the tot1l lfflount of anti-HBs. since the vaccine
consisted of HB~A~/ii:!w only. The· proportion of inti-HBs/d{w) antibodies was
obtained by _subtracting the reduction percenu~e after incubation wHh
KBsAg/1y pooled serun fr0111 the reduction percentige after incubation with
KBsA;/1d pooled ser11111.
R£SULTS
Table I shows a delayed seroconversion rate fgr the reconibinant vaccine
group 1s compared to the plasma-derived v1ccfne group fn the course of the
vaccine study. SIMil1r results were obtaifled for- titres~ 10 lU/1. tl\e
supposed protective level of antibodies.
Tl.BL£ l
SEROCDtlVERSIOll RATE AFTER VACCINATION WITH RECOOlNAICT (10 119) AHO PLASAA-
OE:RIVED (20 ll9) VACCiKE IN HEAL TH CAA£ \IORIC£RS
Month Recombinant Plu1111-derhed RecOlllbfoant Plu1111-derf ved

vaccine vaccine nccine vaccine
Percentage seroconversion Pereent&ge &nti-K8s
! 10 IU/1
1 19( 6/31) 56(14/ZS) 13( 4/31) 40(10/25)

z 77(24/31) 9&(22/Zl) 39( 12/Jl) 74(17/23)
l 90(28/31) 100(25/tS) 74(23/31) 96(24/2S)
6 94(29/31) lOO(ZS/ZS) 87(27/31) 100(25/25)
1 100(31/31) lOO(ZZ/ZZ) 100(31/31) 100(22/22)
Ge011etric aean titres of anti •HBs were significantly lower in the recoEbi-
111nt ncclne group as co111pu,ed to the plasiu-derhed vaccine group at 110nth
2. 3. 6. and 7 (Tabla II).
After three injections f11111les had significantly (p < 0.05) higher 1nti-
HBs titres tMn 1111les In the recombinant vaccine f"UUP (1412 vs. 468 lU/1)
but not in the plasN•dertved vaccine group (6036 vs. 7519 IU/1).
All v1ccinees were ne91tive for HBsAg and anti•HBc 1t 7 110nt11s and had
nol'Wlll 1l1nine tr1nsferase levels In 111 ser, obtained. Table Ill illustrates
the Increase of the relative proportion of 1nti-Kls/1 antibodies frum about
60: at iionth l to ,bout ll>Cn at 110nth 7 following the first injection for
both v1ccine groups as ae1sured by specific absorption. ln any sample at
275
003U3
TASLE 11
GEOMETR!C HEAN TITRES OF AriTJ-!!Bs Ar.ER \'ACC!li ATIO~I WITH RECOMBH:ANT VACCINE
(10 ;: g) ANO PLASHA- OERIVEO 'tACCIKE (20 \19)
Honth R!c0111b,n1nt Viccine Plasma-derived vaccine

CMT in JU/1 Ci'tT in IU/1
l 16.S(nm 6)• 19 . 7(n• l4)

z 13.7(n• 24) 61.8(nm22)0
3 34.S(n.. 28) 177 . 7(n• 25)o
6 69 .0(n• 29) 291.l(n• Z_S)O
7 857.4(n• 31) f 736 .S(n• ZZ) o
1 Responders 011ly O p< 0. 05 Vilcoxon's ...-1nt; sui;i test
_TABLE III
DETEPJIINATION or SUBOETt:Rl'IINA."iT SPECIFIC ANTIBODIES AFTER VACCI:iATION WITH
itECDXBIN"':IT VACCINE (10 \19) A.'lD PLASMA-DERIVED VACCINE (20 1,19) AS OETtil.'IINEO
BY SPECIFIC ABSORPTION
tlonth RetOllbinant vaccine Pl11111A-derived vacci ne

No . : anti• I anti • Ho. I anti- :: I nti-
u~les H8s/a HBs/d sampl es HBs/a Hls/d
· (range) (range)
I 4 60(19- 92)11 39 6 57(22- 99) 42

2 9 81(40- 98) 17 15 83(25- 99) 17
3 18 95(74- 100) 5 23 88(26-100) 11
99(89-100) 24 94(43-100)
6
7
26
3l 99(90-100)
1
1 ·22 97(91-100) '
3
1
Deteniin, tion of aritf-HBs/ 1 i nd anti-H8s/d was limited by the • iniCJII
aaount of ZS JU/1 1nti-118s.
aonth 7 the proportion of 1nti-HBs/1 antibodi es vas at least 90: . In sera

with anti-HBs !. 10 IU/1 at IIOllth l , two out of fovr in the recOllbinant
v1ccine 9r0up and three out of six in the pl 1Sllll•derived vaccine group had
less t han so: anti-His/ a. tn only two cases, one in 11ch group , the anti•
HBs/a percent, ge at 1110nth l va s above 90, suggesting an anaiinestit response.
Ge0112 tric ine1n titres for those vaccinees with I positive anti-His response
·216
003'1LJ
u month I increased to lll:ia IU/1 (n•6) in sera from the recombinant v•ccine
group and to 13i4B IU/1 (n•l3l in sera fro~ the p1as~·dtrived vaccine group,
both at month 7.
DISCUSSION
Table IV comp1'1!s the l"t!sults cf the immunicity of recOllbinant hep•titis a
vaccine of Herek, Sh1rp and Oohllle in our study with results of others as
recently pu!:llished. 1 • ' 1 Severe! lots of vaccine with ■inor differences
in the purification procedure were used. Comparison is ude \n s011e studies
w1th earHer results using pl_H.ii&•derived vaccine from the uiae manuf.acturer.
In our study v1ccination with recombin.ant vaccine and plasma-derived vaccine
too~ place s1Q~lttneously. Seruftl silllples could therefore be handled similar-
ly ind investi91ted with the same batch of na9ents.
lie found ·anti-H9s dHelopaient during•tne first six 1110nths following the
first injection very siMil1r to Scolnick et .al. 1 and Jilg et 11.•. After
the booster ir.jection at month 6 we found, lower g~tric 11e1n t1tre than
observed by others. The proportion of anti•H8s/1 antibodies, h-ver,. was
very similar for the two vaccine groups and increased fl'OIII 60: •t t10nth l
to about 100: •t 110nth 7,
Interestingly, .we noted high titres of anti-M8s at 110nth 7 for those
vaccinees who had •lready shown seroconversion 1t 110nth 1, Tftns in this
subgroup were coaaparable to those 1n early responders fn the pl1s1111-derived
vaccine group. Since we had the lowest seroconversion rate at .,nth 1
observed so f•r for recOlllbinant vaccine (1~). this 111y explain the low
geonietric siean titre lt 110nth 7. The reason for the initial low conversion
rate in our study is unknown. Sex and age ·difference, with other study
groups aay have contributed. Sex and age effects Ny have their most pro-
nounced influence on v1ccin1tion of we1k responden. 11 11 The highest sero-
conversion rate (67i) ind the highest ge0111etric ae&n titre (2749 lU/1) at
11011th 7 were observed by Pap1ev1n9elou et al.' in _ 111le recruits aged 17-19
y&&".
If our observations can be confinaed fn more extended studies, equalizing
the dose of KBsAg in the rec0111bin&nt vaccine preparation to ~t of the
plasma-derived v•ccim! uy favour1bly influence the serocanvers1on rate at
1110nth l 1nd the an>unt of anti•HBs produced after three injections.
AtlCICOWLEDGEtf:HT
We thank Hrs. R.S.Engels-Bakker for prep.aration of the 111nuscript.
277
TABLE IV
IHHUNE 'R[SPONS[ AFTER VACCINATION WITK RECOMBINANT AHO PLASHA-DERIVED HEPATITIS D'vACCIMC AS COHl'AREO FR011 LITERATURE
Authors Dou GeCll!ttric mean ·titres in IU/1 Ho, Hun 19e . No. of Ni>. of Li>t no .
Honth IIIC!n Wlllllen
J 6 7
Rec0111blnant vaccine
Scolnlck et s l. 1 10 \19 II 56 611 \905 15 JJ,23-53 10 5 9]4

Jflg et al. ' 10 1111 9 29 68 21JS 30 ! 5,Zl-34 ll 17 9]4
ti
00 P,pae vangelou et al, 1 10 pg . 11 198 189 270 55 17-U 55 979
Davidson and Krugiwu' 10 " ' 4Z 145 321 1911 51 Zl-30 972
Present 1tudy 17 35 69 . 057 JI JZ , ~0-59 14\ 11 97Z .
10 "'
Pl asma-derived vaccine
Jllg e t 1 1. 1 20 119 15 164 263 4Z99 41 25,21-32 18 23

Present s lud)t 20 117 291 6737 25 30, 22-53 12 ll
zo "'
P1panan9elou et 11, 1 10 119 4 Z78 oz !IZZ7 50
0
0
""'
!:,
,.,.,
003'46
R£F£ i!£HC£S
1. ·szmuness W, Stevens CE, Zang EA, Harley EJ, Kellner A (1981) Kepatology
l: 377-385
2. Stevens CE, Taylor PE, Rubinstein P, Ting RCY, Bodner AJ, S1mg1dharan
HG, Gallo RC (1~85) H Engl J Ked 31Z: 375-376 . .
3. V1lenzuela P, ~dtn• A, Rutter WJ, Alnerer G, Kl11 BD (1982) Nature
Z9B: 347-350
4. HcAleer WJ, 8uyn1k ES, Haigetter RZ; Wlllll)ler OE, Killer WJ, Hilleman MR
(1964) Nature 307: 178-180.
S. Scolnick EM, Mclean ),A, West DJ, HcAleer WJ, Killer WJ, 8uynak EB (1984)
J Alll Med Ass 251: 2812-ZllS .
6. Jilg W, Lorbeer 8, Schrlidt H, Wilske B, Zoulek G, Deinhardt F (1984)
L&ncet II: 1174-1175
7. Devidson N, Krv!jlllan S (1985) Lancet I: 108·109
a. P1paevan9eJou G, Oandalos E, R01J11eliotau-Karayannis A, Rich•rdson St
(1~85) Lancet I: 455-456. · • .
9. P.arlter Lf, Hi)'ll&rd JE, Purcel 1 RH, Hoofnegle JI!, Berquist KR, London iir
(1975) Al:! J Hed Sci 270: 189-195
10. Sllll~'l\eSS W, Stevens CE, Harley EJ, Zang £A, Alter KJ, Taylor PE,
De Vern A, Chen GTS, Kellner, The Dialysis Vaccine Trial Study Group
(1982) N Engl J Med 307: 1481-1486 ..
11. Legler K, Strohntyer H, Ritter S, Gerlich IIH, Thallssen R (1983) Develop
Biol Standard s•: 179-lH . ·
·12. Jflg ll, ~lhoune C, Detnlla.rdt f, Roumel'lotou-tanyannis AJ, Papaev1119elou
GJ, Hushallwar It, Overby LR (1984) J Med Viro•l 13: J7l-178
13. Hollfn9er F'B, Adu! E, Heiberg D, 11elnick JL (19&2) In: Szamtss W,
Alter HJ, Maynard JE (eds) Viral Hepatitis. Phil1delphi1, Franklin
Institute Press. pp. 451-466
14. Hoofn19le JH, Gerety IIJ, Sal&llwood LA, "4rker lF {1!71) Gutroent1rology
72: 290-296
15. He!jt;nk RA, Yan HattUII J, s,h,1 ■ SW, Kasurel N (1982) J Ked Yirol 10:
6~~ .
16. Heijtink RA, De Jong P, Scilil ■ SW, Kasurel N (1984) Hepatology 4: 611·
614
17. Stevens CE, Sz.iness W, GooGll&n AI, Westley SA, Fotino M (1980) L1n,et
II: 1211-1213
279
CD
i
►
Q
::,
I-
v,
003U7
PRDGRM: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,

Study 808

personnel who are negative for hepetit1s B virus
serologic 111arkers.

PRI ARY Richard E. Samp11ner, M.D.

INVESTIGATOR: Chief, Gastroenterology
111 G, Veterans Administration Medical Center
Tucson, Arizona 85723
SECONDARY Timothy R. Morgan, M.D.

INVESTIGATOR: Chief, Gastroenterology
Veterans Administration Medical Center
STUDY LOCATION: Veterans Administration Medical Center

Arizona Health Sciences Center
DATE STUDY INITIATED: April 3, 1984
DATE STUDY COMPLETED: In progress

who are negative for HBsAg, anti-HBC, anti-HBs, have a
nonnal ALT level and have not previously received any
STUDY PROCEDURE: Eligible study participants receive a 1.0 ml (10 mcg

HBsAg) intramuscular injection of vaccine at 0, 1 and
6 months. Vaccine recipients record their temperature
and any local or systemic complaints for five days
after each injection of vaccine.
24741/1
1/15/86
00348
Study 808
STUDY PROCEDURE: A blood sample is obtained from each study participant

(Contd) approximately two weeks before the first injection of
vaccine. Post-vaccination blood samples are obta1ned
at 1, 2, 3, &, e, 12, and 24 months.
All samples are assayed for HBsAg, anti-HBc, anti-HBs
and ALT. Samples 111ay be tested for yeast antibody.
In addition , samples with an ant1-HBs titer >25 mlU/ml
may be tested for anti-! and anti-{ subtype
spec if 1city.

10 mcg Lot 972/C-K444 at 0, 1 and 6 months.
l. Number Vaccinated:
In_iection No.
_L .L _3_
25 25 25
One person who was initially anti-HBs positive

received vaccine. The subject did not display a
boost in titer after one injection of vaccine. A
>50 fold rise in titer was seen after two
injections.
One person who was anti-HBc positive prior to
vaccination and 1 month post vaccination received
vaccine. In all subsequent serum samples the
person was anti-HBc negative. The subject
remained HBsAg negative with . normal ALT levels
through g months of fo 11 ow-up and became ant i-HBs
positive at 2 months. There has been no report of
clinical illness in this individual.
Sero logic data at 7-8 months are available for 23
study participants.
24741/2
1/15/86
Study 808
RESULTS: (Contd) At 7-8 months, 96% (22/23) vaccine recipients

seroconverted ( S/N ~2. 1) and deve 1 oped protective
levels of anti-HBs (mlU/ml ~10). The GMT for al 1
vaccinees was 1711.5 mIU/ml at that time. Among
responders with a titer of S/N ~2.1 and mIU/ml ~10
the Gfi/ll was 2535.7 mIU/ml at 7-8 months.
By 12 months 95% (19/20) of the vaccinees retained
an anti-HBs titer of S/N >2.1 and mIU/ml >10. The
GfJIT for all vaccinees was 631. 7 mlU/ml- at that
time.
Ant1-HBs responses at l through 12 months are
3. Clinical Results:
Clinical follow-up data are available for 25 study
part1c1pants following the first two injections
and for 24 participants fol lowing the third
1nject1on of vaccine. Clinical complaints and
maximum temperatures reported following each
injection are provided in Tables 2 and 3. In
sunnary:
1. Frequency by Ingtion No.

Clinical Cgffipl.aint 1 2 3
Injection Site 20 (S/25) 12 (3/25) 21 (5/24)

SystAlfflie 36 (9/25) 8 (2/25) 0 (0/24)
No serious or alarming adverse reactions

attributabl e to vaccination have been reported.
ALT Elevations
Alanine a11inotranferase levels were normal in all
vaccine recipients except for elevations
approximately 1.5 - 2 times nonnal, 1n three
participants. Case no.'b)csihad an ALT level of 62
24741/3
l /15/86
00350
Study 808
RESULTS: (Contd) at 8 months. To date subsequent ALT levels for

this 1nd1vidual have not been reported. Case nos.
(b) (6) had transient ALT levels of 64 and 90,
respect1 vely, at l month. A11 subsequent samples
through 8 months of follow-up were nonnal. A
reason for the ALT elevations was not ascer-
tained. None of the subjects has showed any
clinical or serologic signs (HBsAg or ant1-HBc)of
hepatitis B.
HBV Markers (Ant1-H8c)

One vaccine recipient had a 2 month
post-vaccination serum sample positive for
anti-HBc. The same serum sarRPle was reported
negative on retest. All subsequent sal!lples
through 12 months were negative. The subject
remained HBsAg negative with nonnal ALT levels.
There has been no report of cl1n1ca1 illness 1n
this individual.
24741/4
1/15/86
Table 1
ANTIBODY RESPONSES FOllOWING VACCINATION WITH REC01'18JNANT HEPATI TIS B VACCIME
STUDY 0(10(1
POl'UlATIOH HEAl lit CAIIE PERSOI IIIEl
DOS£ 10 HCG
LOT CK444
REGJt1£H a, I , ANO 6 HOUTHS
lHlTJ AL SEROLOGY HtGATIVE
I Y. MITH AHU-lfflS I GNT UtlU/IILJ I

l---------------------------------------l-----------------------------------------------------1
I I I R£SPONOU!S I
TIHE
IHONTK!II
l---------------------------------------1-----------------I-----------------------------------I
I SIN>= 2 .1 I HlU/t1L >z 10 I ALL VACCJHEES I SIN>: 2,1 I HIU/nl >= 10 I
••••••••••••••••••••••••••••••••w•••••••••••••••••••••••••••••••••••-••••••••-•••••••••••••••••a•a•a••••••••••• -•••
I
1 l10NTH I UY. 111/241 11% I 8/241 I 2.6 I t7.9 I U. 6
I I I I
2 11014THS I 8 7Y. 120/231 70Y. 116/Ul I 57 .6 I 126.8 I 270,8
I I I I ,
l l10IOHS I ,O:f. 119/UI 81Y. 117/211 I 65 . 0 I 114 . 4 I 186.9
I I I I
6 HOIITIIS I '1l( IU/UI (l]Y. 119/2]) I Ill.] I 136.8 I lU . O
I I I I
7/8 ttOflTHS I 96l( IU/U I 96l( 122/23 1 I 1711.S I 2535.7 I 2515.7
I I I I
lt t10NTKS I 95l( 119/201 9SY. 119/20 I I 631.7 I 945. l I 90.l
I
•···R•w•••·····················••·••··········································•·················•·················
0
0
uf
....I.It
...,..
Table 2
PATIENT COUNT CllNICAl Cot'IPLAJNTS
REtot'IBIHANT HEPATITIS 8 VACCINE
STUDY • oeae
TIU:ATl1tNT
LOT ta.11191!:R : CK4"
DOSI' 10 l1C8
PATIENT CLA3S: HEALTH CAR! Pfll!IOHN£l
I TOTAL VACCJNU:S I 25 PATIENTS I - DOSE l •

1----------------------------------------------------------------------------•
• DAYS POST VACCIHATION • HUllt!EII
CLINICAL •----------------------------------------------------------------------------• MITH
COt1PLAIMTS I O I 1 I t I J • 4 • 5 I IC011PU1MTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••••••••••••••••••••••••I••••••••••
I I I I • • I I
REACTIOH, LOCAL UNJEtT. SITU I 5 I 3 I 2 I 2 I 2 • 1 I I 5
I C 20.07.) I I u.o;o • I 8.0)0 I I a.o;o I C 8.0lO • I 4.07.1 • I I t0.0%1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PAIH I Z I 1 I I I O I I I I I I 2
I 8.0lO • I lt.o;o I I O.Ol(I • I a.o:o I C 0.0:r.1 I I ,.o:r.1 • I I a.o:o
, I • I I
SORENESS I
lt,OY.I • C O.OY.I I I • 1
•
4.07.1 I C
1
It.ox, I 1
l
4.0XI I I • l
lt,DXI I "
•• 1 16.o:o
I I •I I I I •I
TENDEIIN!SS I 1
• 1 I a D I 1 I 0 I 2
I .... o:o I I 4.07.I II o.o:o I I 0.01!1 II 4.0Y.I • I o.oxt I I I a.o:o
I I I I I I
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o.07.1 I I o.a;o • 1 1t.o:o I 1 0.11(1 I I o.o:o I I 1.0:0 I I I 4,0XI
ttCltlllOSIS I o I 1 I 1 I l I I I o I I 1
I , o.ol!t I , ,.ai:, I , 1t.o,n I 1 ,.ol!, I 1 0.0,.1 I I o.o:o I 1, ,.01.1
-----------------------------------l----------l--------•-l----------1----------1----------1----------•----------•-----------
SYSn:ntc I " I " ' t I , I t • II I I •
I I 16.07.1 I I 16.0XJ I I 8.07.) I I 12.0,0 • C a.ox, I I a.o:o I I I 36.0l(I
----------------------------------------------------------------------------------------------------------------------------
&CHOL! IIOOY/GEffERAl I J l ! I J I D
I c 12.0:0 I •.•,o I 8.01.) I I 12.0:r.1 I 1t.o:o I O.OXI I 16.0XI "
I I
F£vtR CTEttP. NOT UPOIITlV I
I• I
0
0,07.) I •
D.Dl(I I
O·
I.OT.I •I I l
••• %) ( •
0.0%1 I •
o.o;o I
1
ft.07.l
I I
fATJG\Jt/MtA~HfSS I z l t t l ·o z
I I a.o:o I lt.Ol!I I 8.Dl!t •I C 8.07.1 I "· 07.1 I a.or., I 8.DXI
HUOACltE
I
I t
8.07.) I
l
,.,,:o C
1 I
I
•.11:0 l I
I
•. •,x, I
0
11.0XI I ..•,:-., I
t
11.0;0 0
0
l,J
IIESPIIIATOSIY I 0 t 0 II 0 1 J
,.ox, I 8.17.1 ( 0.07.t. I• l.9l!I I 0.07.1 ( lt.OXI I U.07.1 •.JI
rv
Table 2 (oont.)
PATIENT COUtlT CLINICAL COl1PL AtNTS
RECOt181NAHT HEPATITIS B VACCIH,
STUDY : 011011
TRfATt1fNT
lOT 11Utl9ER I CK44 ♦
DO!IE lO IICG
PATIENT CU !ISI HU LTff CAIi! PER!IOtHL
• TOTAL VACCIN[E!I I 25 PATUHTS I • DOS! I I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NllffllER
1----------------------------------------------------------------------------•
CLJHICAL
COMPLAI NTS • II I 1 I t I J I 4
..........................................................................................
•
I 5 •
..........•..........
I •
MITH
ICOHPLA I NTS
•.....•..• ,
I •
,
I
SU~SlTIS • O • 1 I III I I I I I I I I l
O.IIIZI. I 4. 01.I . f O.OZI I I O,OZI I I O.OXI I I 0.17. 1 I I I 4. 07.I
I • • t I I I
PHARYIIGITIS ISOSII!: THROATt I O I l • 0 • 0 • 0 I O I I l
11.or.1 I I 4. 0ZI I I o.or.1 I I o.ar., I I •• ,z, I I O.OXI I I I ~.Or. I
I
UPPER RESPIAATOII Y IHFl!CT. , HD!I I
•
11 . llO
I
I I •
I.OlO I I
I •
O.OlO • I
I a I
I. IIXI I I
0
O.OZI
I
I f
l
4 .IZ I
I
I
I l
I I ♦ .or.,
I I I I I I I
.
11115CULOSKELETAL
tffALGIA
I
I
t
1
I
11.IIZI I f
I
I
4 .0ZI I I
I
I
I
1
•
0 I
I
I
I
•
•
0
0
I
I 1 O.OZI I I 1.07.1 I I
♦ . 01. 1
I
I
0 .01.I • I O.OZI • I 0.01. 1 I I
I
• 0
1
4 .0Z)
I
O.Ol!I I I
I
f I
I
I
1
1t .11.1
0 I
0.07.1 •
•I
I
I
I
I I 16.0ZJ
I
I '
I I 4. 0lO
I
.
HECI( PAIIO I 0 I 0 I I 0 I
1.1i1 I 1 O.Ol'!I I I o.o;o • c O,OXI • I • 1
4. 0l!I
I
I I
1 I
4. 0Z I I
I
I I
l
4, 0XI
SIIOULDH PAIN • 1 f O I O I O I O f O I I 1
4.0Z ) I I o.a,o I I 0.0"1.I • t o.o;o f I 0. 07.1 I I O.IY.I I I I 4 .0lO
I I I I I I I
HECK suFFHEss I e I o • o I o I 1 I 1 I I 1
•.,x, II I t .0?.) I
I
I 1.07.I I
I
I O.DXI I
I
I .- .01.1
I
I I 4 .IXI
I
I I f
I
4 .0Y.J
mASTHENU I a I 1 I • I a I a I • I I 1
I I 0.111.J I I 4 .07. I I I 9 .lll!I I I l .lllCI I I 11.o;u I I • • , z, I I I ... oz,
-----------------------------------t----------
PERSOffs WITH COffl'LAIHTS I II Ir----------•----------
!I f 4 Ir----------1----------1----------1----------
!I f 4 I J I I1-----------
U
I I JZ.OlO I I 20.0l'.t I I H.Oi'.I I I zo.oz , I I 16.0,0 I I u .a;o I I I 40.0;l,I
-----------------------------------1----------1
n:Rsons WITH NO COHPUINTS I 17 I ----------r----------1----------1
to • U I 20 I ·---------1----------1----------1
tl I 22 I f
-----------
15
I I 611.91.1 • I 80.07.1 • I 114 .07.1 I I eo.o:o I I 114.1)0 I I 118.07.I I I t 60.0iO
-----------------------------------l----------l----------
P£RSOIIS MITH MO OATA I O I I
l----------1
I t •
----------l----------l----------l----------1-----------
I I I I I • • 0
0
0
I I 1 .17.t I I O. t Y. , I I I.Of.I • I t .OlCI • I O.OiO I I t.07.1 I I I O.OX I
""Ill
""
-
Table 2 (cont.)
PATIENT COUNT CLINICAL COffl'lAINTS
RECOl1BINAlfT HEPATITIS B VACCitlt
STUDT oeoe
TREATl'1tNT
LOT tU\81:R CK,.44
DOSE ia nee
PATlfHl CLASS HEALTH CAR! P!RSOtlfff L
I TOTAL VACCINU!I I U PATIENTS I • 005[ t I

1·-··--·-···-·-------·--··-·-·--····-··--··········-··-··---·········-·--··-·1
I U.T!I POST YACCIHATlOH I tM111[11
CLINICAL I····•·········••·-····•·····•······························ ·................ , MllM
COt1PlAINT!I I I • l I 2 • l I 4 I 5 I ICOttl'UINTS
~•••••••o•••••••••••••••••••••-•••l•••••••••••••••••••••••••••••••• l••••••••••l•••••••••• l•••••••••• •a••••••a••••••••e••••
I I I I I I I I
RUCTION, LOCAL IIHJfCT. !IITEI I Z I I I 1 I D I o I o I I 1
I I 8.0XI I f e.OXI I I 4.0XI I f O.OXI I c O.OXI • I t. OXJ I I I lt.011
-··················--·············1···-···-··1··········1··········1··-·······1··········1·-········1··-·······1·······-···
SOIIEHESS I Z I t I l I o • I I o I • l
I I a.ox, • 1 a.ox, I 1 •·••• I c o.ox, I, o.ox, I c ,.ox, I I 1 1z.ox1
····················-·············1··········1··········•··········1··········1····-·····1·-········1··-·······1·-····-····
!IT!ITU11C I Z I 1 I O I l I O I O I I 2
I I 8.0XI I I 4, 0XJ I I O.OXI I I ,.ox, I I o.o;o I I o.o:r., I I f e.o:o
-----------------------·------------------------------------------------------ ------------------------------------------~
I -
IOiOLE BOOY/G[HERAL •I l l 0 l 0 I 0 2
4. o:o I 4 .01.1 I 0.01.1 I 4 .01.) I O.OXI I I 0 .0:r.1 f a.ox,
I
HVU lTfl1ft. HOT UPOltTt:O I I l
4 .0XI I •
0.07.1 I
a
a.ox, I
0
G.01.1 I •
0.01.1 I I• •
1 .0)!1 I
l
f:I.O)!I
FA1Jmn:/WEAKNE!l9
'
l
• • OX)
I
o.ox, I
0
0,01.1 I
l
•.o:r.1 I
0
,.ox, I •
l!I . I XI I
2
6.01.1
'
HEADACHE I 0
O.OY.I
l
4.07.) C •
0.0)0
0
O.D7.1
• •
1 .07.I f •
O.IY.I f
1
~.01.1
' f
DI6£ST1VE STSTE" I l
4.0X) f
0
0. 07.) I
0
I.DX!
D
o.o::o I
0
0.07.1 I •
0,17.1 (
l
4.Dill
'
AIIDOttlNU PUNS/CRAttPS
• l
•. ,:o 0
0.07.) •
o.oin
a
•• 01.) I •
o.o:u
0
0 .07.1 •
1
4 .0lO
• '
f
' '
NERVOUS STSTt" I 1
••• )0 • 0.07.) f O.OXI I
0
0.07.1 I •
0.0)0 • I 0 ,01.)
1
... ,x,
VfllTICO/IIIZllNU!I I 1 I
' I I O I D I D I I I I
' l
I I 4.07.J • I O.OY.J I I O.OXI I I 0,01.) I I O,Di:I • I 1.01.1 I I I 4. D1.1 0
··---···-···--·····················•-·········1
PEll!ION!I WltN CDIIPlAJNT9 I l I
··········1-·········1··········•··········•·······-·-1··········•-··········
J I l I l I I I O I • 4
0
vi
I I it.ox, • I lt.07.1 I I •• DY.I I I 4. 0)(1 I I •• ,x, I I •• ,x, I I I 16.IX)
""
.t::
Tabl~ 2 (cont.)
PATIENT CtlUHT CLINICAL COttPlAINTS
AECot181NIINT HEPATITIS 8 VACCINE
STUDT , eoe
TIIEATMfflT I
LOT tuaUt I CK4~
005£ 1 10 11CC
PATIENT CLASS : HEALTH CME PERS!lf!HEL
I TOTAL VACCI NUS C 25 PATitNTSI - DOSE t I

1I ----------------------------------------------------------------------------I
DAYS POST VACCJNATIOH I ~ ER
CLINICAL
CDMPLAJNTS
l----------------------------------------------------------------------------1
I O I l I 2 I J I 4 I 5 I Wlnt
ICot1PLAI NTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-------·---------------------------l----------
PEIISONS NllH HO tottl'lAINTS I U
l----------l----------1
I 22 I 24 I
----------1----------1
24 I :!!5 I
----------
H
I----------I-----------
I I U
I C 119.0l'. I I C H .Ol(I I I 96.0iO I I '16.0i!I I 1100.0lO I uoo.ox t I I C 114 .0i!I
-----------------------------------l----------l----------l----------l----------l----------1
PERSOMS NJTK HO DATA I O I O I O I O I O I
----------
O
1I ----------1-----------
I 0
I C 0 .0:r. 1 I I 11 .0lO I C 1.0.1. 1 I I 0.0.1. 1 I C 0.0:r.1 I· l O.OX I I I c t .oz 1
0
Q
i.,,I
I.II
Ill
Table 2 (oont. )
PATIENT COlMT CLINICAL COHPLAlNTS
RECOltllllUNT HEPATI TIS II VACCINE
STUDT 011011
TI!UfflENT
LOT tM1!1£R C1C<t4"
!JOSE 10 t1C8
PATUNT CLA99 HEALTH CME PPl!OMl!L
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES C ts PATIENTSI - 1105£ 3 I
l----------------------------------------------------------------------------1
• OATS POST VACCINATION I N\fflER
CLINICAL
COMPLAIHn
•----------------------------------------------------------------------------1
• 0 • 1 • t I 3 I ft I 5 •
NI TH
ICOffl'lAIHT9
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• l•••••••••• •••••••••••l•••••••••••••••••••••I••••••••••
AlACTIOM, LOCAL UHJl!:CT. SITU
•• 5
I
• 1
•• t
I
I 11
•• I
I
I O
•• I
I 5
I c to.ei:1 • c 4 .tY.J I c e.s;r.1 I c 0.111.1 I 1 1.11.1 I 1 11 . 0:0 I I I to . ez1
-----------------------------------•----------•----------
SOREHESS • 4 • 1
•----------t----------
I t I O
1• ----------1----------1----------I-----------
I • I • I ft
I I 1 6.7Y. I I C 4 .tlO I I e.J?.I I I 1 .117.1 I I o•• Y.I I I 11.07.1 I I I 16.?Y. I
I • I • • I I I
TEHOUfllESS • 1 • o • o I O I o I o I I 1
I I <t.2Y.I • C 0.0iO I I 0.0½1 I C 0.0;:1 I I O.OY.I I I 0 .07. 1 • I I 4. tlO
-----------------------------------•----------1----------1----------1----------
Pllt!ONS NlTH COt1PUINTS I 5 I 1 • t I O
I----------I----------I----------I-----------
I o I O • I 5
I I 20.11:0 • C 4 .UO I C 11 .31.1 I C D.07.1 I I 0.0;:1 I C 11 .07. I • I I 20. 11½1
----------------------------------- •t----------
PUISOOS NI TK NO tlltl'UINTS I9
t----------
I 23
•----------1----------1----------1----------•----------I-----------
f ft f t <t I U I t, • I 19
I C 79.2)(1 I C 95.lllO I C 91 .T/.I I U00.0lO I uoo.o;o I (100.07. t I I I 79 . ti!t
-----------------------------------t----------
PUISOMS w1TK HO DUA I o Il----------1----------1----------
• I a I o 1I
----------t----------
o I o Il----------l-----------
I o
• C I .DY.I • C 0 ,117.1 I C 0.01. 1 I C 0 . 0 1.t • C O. l lO I f I .0iO I I C 0 .0iO
0
0
\..a
\II
c,,.
Table 3
PATIENT COUNT NAXlfflM TEltPEA ATURES
AECOttBINANT HEPATITI S B VACCINE
STUUY 0808
TAEATt1ENT
LOT IIUHBfR CKftftft
DOSE 1 0 11C8
PATIENT CLASS HEALTH CARE PO!IOHH£l
I TOTAL VACCINEES I 25 PAUENTSI - DOSE 1 I

Il---------------------------------------------------------------------------------------1
DAYS POST VltCIHATIOlf I HJl18EA
NAX Tl"PERATURE
CDEC F, Of!All
1•-----·-------·-··---·-----·-----------------·•·····-·------··---------------------·---1
I O I 1 I l I J I ft I S I I
MITH
I KA)( TUtP
ua an•••••••••••••••••••• • • a •••••••• l ••••••• • •• l ••••a••••• l ••••••••• •l •••••••••• • •••••••••• l •••••••e•• l •••a•••• • • le •a••# ■ •ae
I I I I I I 1- I
< 99 I H I u I n I u I u I 1a I I 1a
I t e,.n, I c 011.0:0 I c , 2.0:0 I c ee.o:,o I c .o.,x,
I , as.r1.1 I I , 12.0,n
I I I I I I I I
99 - 99.9 I 4 I 4 I e I 1 I 2 I 2 I I 6
I c u .11.1 I , H.ox1 I c 1.01.1 I , u .,:o I t • .1:0 I 1 ,.s,o I I 1 2-. .0?.1
I I I I I I I I
100 - 100 . 9 I o I o I o I I I o I 1 I I 1
I c , .oio I c o.o,o I c o.oio I , o., ;:, I , 0.0;: 1 I , • .a:o I I 1 4.o:o
------------------------ l----------1----------l----------l----------l----··-·-·
TENPERAME TAKEN I 14 I 25 I H I 25 I 22 Il•---------1---------------------1-----------
21 I I M
I C 96.0Y.I I 1100.0)0 I CU 0.0Y. ) I U 00. t Y.I I C aa.o:c, I I 84 . e ;o I I 1100.0:0
------------------------l----------t----------l----------
n ,,PERATURE NOT TMEN I 1 I t I t
l----------l----···-·-1
I u I J I
----------1
" I
---------------------1I -----------
o
I t 4 .o:u I c 0.01.1 I c o.o:o I I 0.01.1 I I lt ,OY.I I t 16. I Y.l I I I o.o:o
0
0
VI
u,
_,
-
Table 3 (oont.)
PATIENT COIMT " AKil1lWI T[NP£RATUSIES
RECOf18INANT HEPATITIS 9 YACCIH£
STUDT I 0808
TllEATl1£NT
LOT tamaER Cl(4_.
00,£ I 10 NCS
PATIENT CLASS : NEALTH CUE PH!ICIMIEL
I TOTAL YACC IN!ES I 25 PATIENTS t - DOSE Z I

•-------------····-··-·-·-··------------------------------------------------------------•
I OATS POST YACCINATIOH • Nllt111ER
NAX Tf l1P( RATUllf 1--------••·---···--················•···· ···-····-··•···--·••----·--------------------•·• MI TH
t O[G F , OHU • t I 1 I t I J I 4 • 5 I I • N,\X TEPII'
••••••••••••••••••••••••••••••••••• ••••••••••••••••••••••••••••••••••••••••••••••••••••••• •••••••••••!•••••••••••••••••••••
flOllrtA l
•• 1
•• 1 I• 1 II 1 I• l
II l I• II 1
I I 'i . 81. 1 I ( 4 .8% 1 I l • • SY. I I l 4 . 8l0 • I 4 . 8 )!1 I I 5 . J l!I I I I 4 . lllO
.I I I I I • I I
< ,, I n I n I 19 I 1a I 19 I
11 • I u
I ( ff. 5)0 • I 90 .s:o I I 90.sx, • l as .r.o I I 90.S)!) • I 89. 5)0 • I I 71 . 47.1
I • I • I I I I
" - n .9 I 1 I 1 I 1 I t I l I 1 I I s
I l 4 .11.1 I l 4 .1%1 I I 4 .SY. I I l , .sin I I 4.1)0 • I S.JlO I I l n. a:o
-······--·····-·······-·•······--·-1----------l----------l----------l----·-----1--·-------1
TEttf'EIIATUIIE TAKl!N I n I ti I n • ti I n I u I --------·------------1
I
····-------
n
I • 94, a1.1 I I M.o;o I , a, .ox, I , a1o .ox, I t 84 .0lO • 1 1,. , io • I c 81t .1:o
---········--------·----•·-·-·---·-1-------··-l--·-------l----------l·-------··•----------
TUff'lllllUII£ Mill TMtH I " I 4 I 4 I 4 • 4 • 6
l----··------····-----l------···--
I I 4
• I 16 . 0lO I t 16 . 0lO I I H .tlO I t 16 .0XI I I 16.0lO I I 24.0l!I I I t 16.IX I
0
c:,
I.Pl
VI
OD
Table 3 (cont. )
PATIENT COUNT HAXIHUH T[t1P[AATUR[S
R[CClttBltl.tNT HEPATIJIS 8 VACCINE
!11\JIIY 0808
TRUTtttNT
l OT flUll9£R I CK444
DOS[ I 10 11C8
PATIENT CLASS: H[AlTH CAJIE PfRSQNNEl
• TOTAL VACCJN£[9 I 25 PATJENTSI • DOSE 3 •

1---------------------------------------------------------------------------------------•
I OATS POST VACCtNATlON I NJ118EA
HAX TENPERATURE
IDEII F, Ol!AU
f----------····-··-----------------•------•-·•--·---·-•----------·----------------------1
I O • 1 I t • J I 4 • s I •
WITH
• HA)( TE"'
•••••••••••••••••••••••••••••••..•••••••••••••I••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
I I I I I • I I
< '9 I 14 • U I 13 • 1t I U • U • • U
• 1100.0:0 I c •2 • .io • 1110.01.1 • noo.o)(t I 1 9o.•;o I 1100.0:0 • • 1 es.r1.1
I I I • I • I •
n - 99. 9 • o • 1 I o • • I 1 I o I I t
• I 1. 0;0 • C 7.11.1 • I 0.0%1 • C o.o:o • C 9.llO I C 0.0-/.t I I C 14.11.1
------------------------l---------·1----------1----------1----------•----------l----···-·-1·--------------------1
TENPfRAT\lllE TAKEN • 14 • 14 • 1l • 1t I 11 • 1l • • -----------
14
I 1 56,07.1 I c 56.o;o • 1 si.o:o • c 48.oio I c 44.o:o I , s2.o;o • I , 56.o:o
-----------------~------
TENPERATUR£ HOT TAKEN •l----------
11 I•----------l----------•----------1----------1----------1
11 I 12 I U I lit I 12 •
---------------------1-----------
• 11
I I 44 .0)(1 I I ti♦ .o:o I I 48.01.I I I SZ.0l!I • I 56.0iO I I 49.0l!I • I I lt4.01.I
0
0
vi
;JI
.0
00360
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepat1t1s 8 Vaccine,

Study 809
PURPOSE: To evaluate antibody and clinical responses to various

doses of vaccine in the following initially
seronegative populations:
1. Healthy Ch11dren (1-11 years of age)
2. Healthy Adults
Lot H 972/C-K444 (10 mcg HBsAg/ml)
985/C-K732 ( 5, mcg HBsAg/ml)
PRINCIPAL Drs. Stanley Plotkin and Stuart Starr

INVESTIGATOR: Division of Preventive ~d1c1ne
Joseph Stokes, Jr. Research Institute
Children's Hospital of Philadelphia
34th Street and Civic Center Blvd.
Philadelphia, PA 19104
STUDY LOCATIONS: The Pediatric Medical Associates

420 Township Line Road
Havertown, PA 19083
George A. Starkweather, M.D.
1001 Pennsylvania Avenue
Havertown, PA 19083
STUDY POPULATION: The study population consists of healthy children

(ages 1-11 years) and healthy adults who are negative
for HBsAg, anti-HBc, and anti-HBs, have a nonnal ALT
level and have not previously received any hepatitis B
vaccine.
PROCEDURE: Children 1n the study receive a O. 5 ml ( 5 mcg HBsAg)

or a 0.25 ml (2.5 mcg HBsAg) intramuscular injection
of lot# 912/C-K444 vaccine at 0, l and 6 months or a
0.5 ml (2.5 mcg HBsAg) or 0.25 ml (1.25 mcg HBsAg)
injection of lot# 985/C-K732 vaccine according to the
25291/1
1/3/86
00361
Study 809
PROCEDURE (Contd): the same time schedule. Adults receive a 1.0 ml (10
mcg HBsAg) intramuscular injection of lot# 972/C-K444
vaccine at 0, 1 and 6 months. Vaccine recipients (or
the parent or guardian in the case of a minor) are
asked to record their temperature da1ly for five days
after each injection of vaccine and to record any
local or systemic complaints that they may have during
this period.
A blood specimen (10-15 ml) is obtained from each
prospective vaccine recipient one to two weeks before
the first vaccination. Post-vaccination bleedings are
obta 1ned at 1 , 3, 7 and 12 months from some of the
children and at 2. 6, 8 and 12 months from others.
Post-vaccination bleedings are obtained from adult
vaccine recipients at l, 2, 3, 6, 8, 12 and 24 months.
The samples are assayed for HBsAg, ant1-HBc, anti-HBs,
and ALT. Samples niay also be tested for yeast
antibody and those with an anti-HBs titer ~ 25 mIU/ml
may be tested for the proportions of anti-! and anti-d
activity.
RESULTS: HEALTHY ADULTS:

10 mcg Lot I 972/C-K444 at 0, 1, and 6 months
Injection No.
_1_ J_ _3_
18 17 17
Serolog1c data are available for 11 participants
at 7/8 months. One hundred percent (ll/11) of the
protective levels of anti-HBs (mIU/ml ~10) at that
time. The GMT at 7/8 months for a11 vacc1nees was
955. 7 mIU/ml.
Among the participants with serology data
available at 12 months, 100% (12/12) were positive
for anti-HBs (mlU/ml ~10). The GMT for all
vaccinees was 448.7 mIU/ml.
25291/2
1 /3/86
00302
Study 809
RE SUL TS (Contd) : Refer to Table 1 for ant1-HBs responses and GMTs

for other t1M intervals.
3. Clinicaf C0111plaints:
Type of Freouencv in I bv Iniection No.

Complaint l 2 3
Injection 17(3/18) 24(4/17) 6(1/17)

Site
Systemic 6(1/18) 6(1/17) 12(2/17)

complaints by injection number. f!laximum
temperature data are provided 1n Tables 3.
There were no serious or alann1ng reactions
25291/3
l /3/86
00363
-----•-------------·
..o•. •.
rI •t> •1t
• • ~ D ~ ~ •
■ 0 • • t I I •
'.~-. .
" *0 ""G Ill\
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~ ~
..
•
..
.,JO .. o, ,.:, it
l[ . *
.,, a;. 'I>
~
w
*
•
••
a • •
...z z
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• - - - - - - - - - - - - - ·•
... ...v> I
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...... tt
..
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...z
---•-------------·
.
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e
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~ -# ..,_ N ,-. ► ,.._ *
ff-
z z ,p • • • fl,
.,.. 'It C ,.._ ,-. ,.... U"I CD 'A'
,,.
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. ..
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> ~
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c,,,
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..
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ff.
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:c "'.•.
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I I
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.......
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:,
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- ,
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,...
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~ .. fl.
f-, " n, C, r..: U"I N -. ..c i'r

u ~'-'"""'V<....t_...,.-c,.
'.J
...J i ► ...... '-' ..., -~
Z:-f) ·:I
<
> '
:.> 1>
-R
,n
~
,: -.i:f . ,, r-" H :.1 H ~ ~>
:: ,s: {; 0 ." , , _
- • 0O ... •
"';s <> C> -1>
...
_.' 0,:;. - ~
.:.
.,., z .;; *
- -... - - - - - - - - - - - - - "t
•.:, ":J," 0
- :r ·~
.t
.JI -
•
~
i :-
-<:·
,"j
....,:-
.•
,... -~ -...'
,.. ....
....
0
,."),
,c;
~
.: I
I ., .,. ' '·• '
, "\
,:
.,
'
-
..... V
..'
V
·,
I
·-·
..J
=-·
I
..,.' .-:; .:-
;
;, :
•
..
:
.,;
: : :
..
:
~;
~·.
~
I ("· ,- .;~
t ~, ~
I I ... : ~i--
• - - - - - m - - -- - - - - - - - - -
0
:~ *~
Q
i ;-
-: .
,...
_, . ....
.,.
•. "'I
...
.
::,
...
··~
.... -. "" -~
:~
· "' ~
"';
_)
-'
: )
,_J · ·,:
I
'
-~
..., :r
~
=- ------------- .,.
-•~
~
Table L
PAT!eNT COUNT CLINICAL COMPLAINTS

RECOMBINANT HEPATITIS 8 VACCINE
STUDY 0909
TRE ATMENT
LOT NUMBER CK444
DOSE 10 MCG
PATIENT CLASS HEALlHV ADULTS
-- - --- ---- ------------------------------------------------------------------------------------------------------------

I TOTAL VACCINEES ( PATIENTS) - DOSE 18 I 1
CLINIC AL
l----------------------------------------------------------------------------
DAYS POST VACCINATION
1----------------------------------------------------------------------------I
1I NUMBER
WITH
COMPLAINTS I O I 1 I 2 I 3 I 4 I 5 I I COMPL AI NTS
··································· 1· ········· 1·········· 1· ········· 1·········· :·········· 1·········· 1·········· 1··········
REACTION. LOCAL (INJECT. SITIE) I 3 I O I O I O I O I O I I 3
I ( 16 . 7%) I ( 0.0%) I ( O.Oll.) I ( 0 . 0%) I ( O.Oll.) I ( O. Oll. ) f I ( 16 . ?ll.J
-------- ------ ---------------------1----------1----------1----------1----------1----------1----------1-
I I I I I I I
-- -------1-----------
I
SOREHESS 2
I
O
I ( II . Ill, ) I(O
O. Oll. )
O
I( O O
O. Oll.) ( (
I
O. Oll. ) I (
I
2
O. Oll.) I (
I
0 . 0%) (
I
I ( 11.l ll )
I
STl f FNESS/TIGHTNESS I, Io I 01 01 01 o I I
I ( 5.6%) I ( O. Oll. ) I ( O.Oll.) I ( O.Oll.) I ( O. Oll.) ( O.Oll.) I I ( 5 . 6 11 )
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
SVSTEr.tlC I 1 I O I O I O I O I O I I I
I < s .sll. J I < o.Oll.) I < 0.011-, I < 0 . 011,J I < 0 . 011,1 I < 0.011,J I I c 5 . 6 ll J
---------------------------------- ---------------------
1 I
------- -----------I ----- --- --------------------- ----
WHOLE BODY/GENER AL I o I o I o o I 0
5 . 6 1' ) 0 , 0ll.) I ( O. Oll.) I ( 0.0%) ( 0 . 0%) I 0 . 0'11) '
5.6"-)
I I I
FEVER (TEMP. HOT REPORTED) 1 o I o o o I 0
5.6,) O . Oll.) I { O.Oll.) ( O.Oll.) ( 0 . 01') I O.Oll.) '
5. 6ll.)
I I
HEADACHE o 01 o 01 o I 1
( 5.6ll. l I ( 0.01') ( O. Oll ) ( O.Oll) ( 0 . 0,1 I < 0 . 0, 1 I I ( s . 6 ,)
;;;;~~S-WtTH- COMPLAlNTS------------1------3---1------0--- ------0---1--- --- 0--- ------o---,------o---,----------1------3----
--------- - --I- <_ 16 . 71' )_,_ <__ o.o,i.J __ <__o.o,i. J_I_ c__ o.o• >_j_c __ o.011,1 -1- <__ o . o%J _, _________ _ ,_<_ 15:111,J __
PEIISONS WITH NO COMPL AINTS I 15 I 18 18 I 18 I · 18 I 18 I I 15
I ( 83 , 31' ) I (100.01') (100 . 0ll.) I {100 . Dll) I (100 . 0ll) I (100 . 0%) I I ( 8J . 3ll )
-----------------------------------1----------1----------1----------1----------
PERSONS WITH HO DAT A I O I O ( 0 I O
1----------,----------1----------1-----------
I O I 0 I I 0
I ( O.Oll.) I ( 0 . 0,1,} I ( O. Oll. ) I ( O. Oll. ) I ( O. Oll) I ( 0 . 0%) I I ( O. Oll )
0
0
"'
a-
~
-- -··--- - - - -
Table 2 ,cont)
STUDY 0809
TRE ATMENT
LOT HUMDl!R CK44 ◄
DOSE 10 MCG
PATIENT CLASS HEALTHV ADULTS
I TOTAL VACCINEES ( 17 PATIENTS) - DOSE 2 f

1----------------------------------------------------------------------------,
I DAVS POST VACCINATION f NUMBER
CLINIC AL
COMPLAINTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I 3 I 4 I 5 I WIT H
I COMPLAINTS
·············· ····················· :····· ·····1··········1·········· 1··········1··········1··········:··········1··········
REACTION, LOCAL (INJECT , SITE) I ◄ I O I O I O I O I O I I ◄
I < 23.S'4l I < o,o"-> I < o,o,r.J I < o.o%J I ( 0 . 0,r.1 I I o . OY.J I I < 23 . 5,r.J
-----------------------------------1----------1----------1----------
SORENESS I I O 4f O
1----------1----------1----------1----------1-----------
I O I O I O I I 4
I ( 23 . 5'4) I ( O.OY.) f ( 0.0Y.) I ( 0.0%) I ( 0 . 0%) I ( 0 . 0"-l I I ( 23 .S,r. )
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
SVSTEMI C f O I O I O I 1 f 1 I 1 f \ 1
I c o . o.,_ J I < o . OY. > I < o. o,_ > I < 5 . 9,r. J I I s . 9,r.1 I I s . 9,r. 1 I I < s . g,r. >
------------------------------------------------------------------------------------------
1 I I
---------------------------------
I I
RE SP I RA TORV I O I O O I 1 I 1 I ) ) 1
o . o,r.J I < o.o,r.) < o . o,r.J I < 5 . 9,r.J I c s.9'41 l ~ . 9%1 I I c s . 9,r.J
PHARVIIGITIS (SORE THROAT) I O
I
I
0 . 0%) I (
t
O
0.0'4) I( O
0.0'4 )
O
I
I
I
I
( 0 . 0,.) I ( 5,9,r.) (
I
I
I
5 . 9%) I
I
I
I
I (
I
1
S.9,r.)
UPPER RESPIRATORY INFECT., NOS I O I O .
I < o.o,r.J t < o.o,r.)
0
< o.o,r.J
1 I 1
< s.e,., I < s . 9'4J I
0
0 , 0,.1 I < 5.9%J
PER~ONS-;;~H-COMPLAlNTS--- ----- ----1---- - - .. - - · 1------0---1------0---1------1---1------,--- ------1---1---------- ------ ◄----
! c zJ . s,r.J I < o . o,r.J I C o.o,r.J I < s.9,r.J I I 5 . 9,r. J I I 5.9%1 I l 23 . 5%1
-----------------------------------1I----------1----------1----------
PERSONS WITH NO COMPLAINTS I c100.011.1
17
13 f 17 1----------1----------1----------1----
I I I16 16 I --- --- I-----------
16 13
c 76.5%) I c100.o,i.1 I c 94.1.,_l I I 94.111.l I I 94 . 1%) I I< 76 . S'!l.l
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
PERSONS WI TH NO DATA I O I O I O I O I O I O I I 0
I < o . o,r.) I c o.o'4J I C o , o,r.) I l o,o,.l I I 0 . 011, 1 I I 0.0,.1 I I l 0 . 011.1
0
0
u,I
0-
\JI
Table 2 (c:ont)
STUOV 0809
TREATMENT
LOT NUMBER CK444
DOSI!. 10 NCG
PATIENT CLASS: HEALTHY ADULTS
I - ------------------------------------------------------------------------------
TOTAL VACCINEES ( 17 PATIENTS) - DOSE 3 I
1----------------------------------------------------------------------------1
I OAVS POST VIICClH,HION I NUMBER
CLINICAL
COMPLAINTS
l-----------------------------------•----------------------------------------1
I O I 1 I 2 I 3 I I S I
WITH
I COMPLAINTS 4
REACT I OH, LOCAL (INJECT. SITE) II

I (
O II
o . O'llo) I <
D
D.O'llol I <
I
s.U'llol
I
·································••1••······••1••······••1••······•·1••······••t••······••1••······••1••······••1••········
I
I
D
o.O'llol I <
II O
D,0%1 I <
II o
o.O'llol
II
I
' II
I I
1
s,9,.)
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
SORENESS I O I O I 1 I O ) 0 ) 0 I I I
I I O. 0'11,) I I O, 0'11,) I ( 5 . 9'11,) I ( 0. o,r,) I ( 0 . o,r, I I ( 0 . 01') I ( 5 . 9,.)
-----------------------------------1----------1----------1----------1----------1----------1----------1
SVSTEMIC I 1 I I I 2 I 2 I I I O I
----------1-----------
2
I l S . 9'l) I ( 5 . 9'11ol I I 11.B'llo) IC 11.Bll.l I< 5.9ll.l I< 0.011.) I I I 11 . B'llol
----- ------------ --------------
RESPIRATORY 1
5 , 9,r,)
I
5 . 9,r,)
I
5,9'11,) '
5. g,r,)
1
5 . 9'1.)
0
0 . 0'11,)
'
I
I
I
5 , 9ll.)
I
UPPER RESPIRATORY INFECT., NOS I I I I
!1.911.) 5,9,.) 5.911) '
5.9'11,) '
5 . 9'11,)
0
0.0'11,) I
I
I
5 . 9'11,)
MUSCULOSKELETAL 0 0 1
0 , 0,.) 0. O'llo) 5.9111 '
5,911,)
0
D,O'llo)
0
0 , 011,)
I
I
I
5 . 9'11,)
I
NECK PAIN 0 0 I 0 0 0 I 1
0.0'11,) O.O'llo) 5 , 9'11,) 0.0'-) o . o,r,J 0 , 0,.) I 5 . 9'11,)
I
SHOULDER PAIN 0 o I 0 0 0 I
0.0'11,) 0.0111 I
I
'
5,9'11,) 0. O'I.) 0,0'11,) 0.0'4) I
I
5.9'11, )
ARM PAIN -
I
0 0 I 0 1 0 0 I 1
0.0'llo) 0 , 0'11,) I 0.0'11,) 5,9'11,) 0.0%) 0,0Y.) I 5 , 9'11,)
I
OTHER
DIGESTIVE SYSTEM
(
(
0
0 .Oll)
0
o.o,.> I
I
I (
I
I
(
0
0,0'11,)
0
0.0'11,)
·I
I
I
5 .9 ... ,
o.~,.)
II <
II c
0
o.o,.,
I
s . 9'11ol
I
I I
I
I
I <
0
0.01'}
0
0.0'11,)
(
(
0
o . o'lloJ I
0
0 . 0,r.1
I
1
I
I
I(
I <
I
5 . 9%)
I
5 , 9'11,)
I I I I I
01-.RRHEA I 0 I 0 0 I I I 0 I 0 I I I
0,0'11,) I c 0.0'11,) 0.0,c,1 I c S , 9,C,) I ( o.o,c,) I ( 0 . 011,1 I I < 5 . 911,)
0
0
~
0-
0-
Table 2 (cont)
STUOV 0809
TREAT MENT
LOT NUMBER CK444
DOSI! 10 MCG
PATIENT CL ASS , HEALTHY ADULTS
I TOUL VACCINEES ( 17 PATIENTS) - DOSE 3 I

1----------------------------------------------------------------------------1
I OlVS POST VACCINATION I NUMBER
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------I
I O I 1 I 2 f 3 f 4 I 5 I WITH
I COMPLAINTS
0 0•••••••••••••••••••••••••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1•••••••••• ••••••••••1•••••••••• 1• •••••••••
I I I I I I I I
muse,, I o I o I o I I I o I D I I
I ! o.o" J I < o.O"l I < o.o"> I C 5 . 9%) I < o.o'IL> I I o.o"> I I c 5 . 9">
-----------------------------------1----------
PERSONS WITH COMPLAIHTS I I
1I ----------1----------1----------
I I 3 I 2
1----------1----------1----------1-----------
I I I O I I 3
I ( 5. 9") I ( 5 . 9") I ( 17. 6%) I C I 1 . 8%) I ( 5 . 9") ( 0 . 0 %) I I ( 17. 6l')
-----------------------------------1----------1----------1----------1----------1------
PERSONS WITH NO COMPLAINTS I 18 I 16 I 14 ( 15 I 18
---- ----------1----------
17 I·
1-----------
I 14
I < 94. l'!L) I t 94. 1'll I < 112.4%) I < 811 . 2%1 I ·< 94. 1") <100.0"> I I < 82.4"1
-----------------------------------1----------1----------1----------1----------1----------
PERSONS WI TH NO DATA I O I O I O I O I O (
----------1----------1-----------
O I I 0
I ( 0 . 0%} I ( 0 . o" l I ( 0 • 0% l I ( 0 • 011.) I ( 0 • o" l I ( 0 • O'!L) I I { 0 . O'llo)
0
0
""......c,-
Tablte _,
PATIENT COUNT MAXIMUM TEMPERATURES
STUDY 0809
TREATMENT
LOT HUMBER CK444
DOSE 10 MCG
PATIENT CLASS : HEALTHY ADULTS
I TOTAL VACCJNEES ( 18 PATIENTS) - DOSE 1 I

1---------------------------------------------------------------------------------------1
I DAYS POST VACCINATIOl'I I l'IUMBER
MAX TEMPERATURE
( OEG F. ORAL)
l---------------------------------------------------------------------------------------1
I O I 1 I 2 . I 3 I I s I I
WITH
1 MAX TEMP
4
······················•• 1I ••······••1••······••
I
1••······••
I
1••······••1••······••1••··
I I I
····•· I1••·······•1••······•• 1••········
I
l'IORMAL I 21
l8.2t.) I (
1
3
21.4%) II ( 3I
23.111) I (
I
31
23.1'11) I
I
(
3
21 . 4%)
I
I (
I
31
21.AlL) I
I
I
I
I
3
21 .4lL)
< 99 7 I 10 I 10 I
e I 11 I 9 I I 6
83.15") I < 11 . 4,.) I C 76.91') I C 61.5'11) I ( 78.6'11) I I 64.31'1 I I 42.9,C,)
I I I I I I I
99 - 99 . 9 1 I 1 I o I 2 I o I 2 I 'I 4
9.1 ... ) I ( 7.llL) f ( O . OlL) I ( IS,4lL) ( 0 . 0 ... ) I ( 14 . 3 ... ) f I 28.Gll.)
I I I I
101 - 101, 9 I O O O DI 01 I
9 . 1,.) ( 0 • Q'll,) ( 0 . 01' J ( 0 • 0 '11, J ( I (
0 . 0'11) 0 . 0'11) I ( 7 , I% J
------------------------,----------
TEMPERATURE TAKEN , 1
----------
14
----------
13
----------
13
----------1----------1---------------------
14 I 14 I -----------
14
( 81,1'11) ( 77.8,C,) ( 72.2,C,) ( 72.21') ( 77.8%) I ( 77.8'11) ( 77 . 8,C,)
TEMPERA~~RE-NOT-TAKEN---1------7---1------ .. --- ______ 5 _________ 5 ___ ------ .. ---1------.. ---1---------------------,------4----
I < 38 . 9"1 I < 22 . 2t.J ( 21 . &'lll < 27.Bt.l I ( 22 . 2,.J I c 22 .n> I I c 22.2'!IJ
0
c:,
u,I
c,-
CIII
Table 3 (cont)
RECOMBINANT HEPATITIS B VAC(INE
STUDY 0809
TREATMENT
LOT NUMBER CK444
DOSE 10 MCG
PATIENT CL ASS : HEAL THY ADULTS
I . TOTAL VACCJNEES ( 17 PATIENTS) - DOSE 2 I

l---------------------------------------------------------------------------------------1
I o-.vs POST YACCINIITION I NUMBER
MAX TEMPERATURE
(OEGF .. ORAL)
1-----------------------------------------------------------------
I 0 I 1 I 2 J 3 J 4 5
---------------------1
I
WITH
IMAX TEMP
~·····················•• 1••········
I I ·········· ········••1••······••1••·····~··
I I .......... ········•• 1••······••1••········
I
NORMAL I O I I I I 1 I 1 2 I 0
t c o . oll.J I < 10.0•> < 10.0•1 I < 10.0""1 I c ,, . ,,.,, < 22 . 2,.,, I c o.o.,.,,
I I I I I
< 99 I 10 I 8 1 I 8 I e s I 6
I (100 . oll.) I c eo.o•> < 10.o•J IC 80.0ll,) IC 88.9ll.l < 66 . 7ll,J I c so.o,.,
I I I I I
SIii - 00. 0 I 0 I 1 2 I 1 I O I I '°'
I c o . o,.,, I c 10 . 0,,_l I c 20.0ll.l I c 10 . 011) I < o.Oll.l < 11 . ,.,.,l I c •o.O,.l
------------------------1----------1----------1----------
TEMPERATURE TAKEN I 10 I 10 I 10
----------1---------
10 I 9
- ----------1---------------------1-----------
9 I I 10
------------------------1-(-58 . 8%1_1- c_s8.8ll,J_l_c_s8.8ll,J __ c_s8.8ll, J _\_<_s2.9%1 _ _c_s2.0%J -1------ -- - ------ --- --- 1-c_se.e"" l __
1
TEMPERATURE NOT TAKEN 1 1 1 1 I 1 1 I e I e I I 1
I ( 41.2ll,) I ( 41 , 2ll, ) I ( 41 . 2ll,) ( 41.2ll,) I ( 47 . lll,) I ( 47. Ill,) I I ( 41.2%)
0
0
ul
c,-
-0
Table 3 (cont)
STUDY 0809
TRl!ATM~NT
LOT NUMBER Cl<444
OOSE 10 MCG
PATIENT CLI.SS HEALTHY ADULTS
TOTAL VACCINEES ( 17 PATIENTS) - DOSE 3
MA~ TEMPERATURE
(DEG F . OflAL I I
I
---------------------------------------------------------------------------------------1
O I 1 I 2 f
1-----------------------------------------------------·--------------------
3 f 4 I 5 I -- -------
I
I NUMBER
----II WITH
TEMP MAX
................. ....... ,.......... ,.......... , .......... ······ ··••1• •····· ·••1••········ .......... ,.......... ,......... .
I I I I I I I
NORMAL I 1 I I I 2 I f 2 f 1 I I 1
I c 12 . s ,. l I c 12 . S'II. ) I< 28.6,. 1 < 12 . S'll.l I< 25 . 0'll. l I< 12 . s'II.) I I c 12 . s11>
I I I I I I
< 99 I 6
t I 75 . D'Kl I
I
t
s I
1s . o,. > t < 57.
•
,,.1 1 I s I 1 I
c 87 . 5'11. ) I c 62 . s ,. > I c 87 .Sll l I
I 6
I c 1s.011>
I I I I I I I
99 - 99 . 9 I 1 I t I o o I o I o I I o
t < 12.s,. > I I 12.s'll. l I c o.o'II. ) C o. o'II.J I c o. o'II. ) I < o.0'11.l I I < 0.011 >
I I I I I I I
100 - too. 9 I o I o I o o I 1 I o I I o
I < 0.0'11. l I < o.O'II. I I < o . 0 '11. I c o . O'll. l I < 12 . s'II.J I I o . 0'll.l I I < o.o'II. )
I I I I I
101 - 101 . 9 I( o I
0 . 0 '11. ) f
o I
( 0. Oll )
1
( t 4 • 3'11. I
o I o I o
( 0 • o,c,) I ( 0 . 0 '11. ) I ( 0 . 01. l I ( I 2 • 5'!C.)
------------------------ II ----------,----------
TEMPER ATURE TAKEN 8 I 8
----------
7
----------1----------1----------
8 I ( 47.18 '11. ) I ( 47 . 811, ) ---------------------1f
-------8 ----
I ( 4 7.1 '11. ) f ( 47.t ll ) ( 41.2'11.) ( .. 7.1 ll ) . I ( 47 . 11.)
------------------------1----------1----------
TEMPER ATURE NOT TAKEN I 9 I 9
----------
10
----------1----------1----------1----------
9 I 9 I 9 I
-----------1-----------
I 9
I c s2 . 9 ll l I c 52 . 9 ,. l C 58 . 8'11. ) c 52 . 9'11. l I C 52.9'11.l I < 52.9'11.) I I < 52 . 9 '11. )
0
0
""
.....
0
--
00
>
Q
::,
I-
V)
00371

Study 811.
PURPOSE: To evaluate antibody and clinical responses to several
<lose levels of conmerc1al hepatitis B plasma derived
vaccine (H-8-VAX) and yeast recombinant hepatais B
vaccine in the following populations who are initially
seronegative for hepatitis B virus markers:
l. Predialysis Patients
2. Health Care Personnel
Lot# 974/C-K446 (20 mcg HBsAg/m1)
Hepatitis 8 Plasma Vaccine
Lot# 1510J (20 mcg HBsAg/~1)
PRINCIPAL Peter J. Grob, M.D.

INVESTIGATOR: Section of Clinical I111nunology
Department of Medicine
University Hospital
Halde11weg 4
CH-8044 Zurich
Switzerland
SECONDARY U. B1nswanger, M.D., Professor
INVESTIGATORS: Department of Me<licine
Nephrology Section
University Hospital
Zurich
C. Descoeudres, ~.D.
Heniod1alys1s Station
Inselspital
Berne
A. Blumberg, M.D., Professor
Nephrology
Kantonspital
Aarau
A. Hany, M.D., P.O.
Hemodialysis unit
Kantonsspital
W1nterthur
H. Iseli n, ~. D.
Hemo<lialysis Unit
Neumunster Spital
Zurich
251&1/1
1 /7/Bf>
00372
Study 811
SECONDARY K. Zaruba, M.D., P.D.

INVESTIGATORS: Hemod1alys1s Station
(Cont.) C1ty Hospital Waid
Zur1ch
W. Herwig, ~.D.
Hernodialysis Station
Kantonsspital
Chur
H.-J. Gloor, ~.D.
Hemodialysis Station
Kantonsspital
Schaffhausen
J. Nadig, M.D.
Hemodialysis Unit
Kantonsspital
Winterthur
H. I. Joller-Jemelka, M.D.
Section of Clinical I11111unology
University Hospital
Zurich
STUDY LOCATION: University Hospital

Haldeliweg 4
CH - 8044 Zurich
Switzerland
DATE INITIATED: April 10, 1984

STUDY POPULATION: One study population consists of 59 predialysis

patients who have rena1 disease with functional
impairment or end-stage renal disease that will
shortly require dialysis treatment. The other
population is comprised of 11 health care personnel.
Subjects in both populations must be adults of either
sex (pregnant women excluded). They must be initially
negative for all hepatitis B serologic markers, have a
normal ALT level, and must not previously have
25161/2
1/7 /86
00373
Study 811
PROCEDURE: Pat;ents are randomly assigned to one of 5 groups.

Health care personnel constitute a sixth group.
Vacc1ne/Oose/Regiraen
Recombinant vaccine; 0.5 ml ( 10 mcg)
at 0, l and 6 months
2 Recombinant vaccine; 1.0 ml ( 20 mcg)
at 0, 1 and 6 months
3 Recombinant vaccine: 2xl.O ml (40 mcg)
at 0, 1 and 6 iaonths
4 H-8-VAX; 1.0 ml (20 mcg)
5 H-B-VAX: 2xl.O ml (40 mcg)
Recombinant vaccine: 0.5 ml (10 mcg)
All injections will be intramuscular. Patients in
Groups 3 and 5 will have the vaccine administered in
divided dose (i.e., 2 injections - one injection in
each of two contralateral limbs).
Vaccine recipients will be asked to record their
temperature for 5 days after each 1nject1on and to
note any local or systemic complaints. Study
participants will be bled 1 to 10 days prior to
vaccination to verify eligibility for the study.
Fol low-up samples wi 11 be obta 1ned at 1, 3, 6 and 8
months following the initial vaccine injection. Blood
samples w111 also be obtained at 12 and 24 months from
subjects who are positive for anti-H8s at 8 months.
All serum samples will be assayed for anti-HBc,
ant1-H8s, HBsAg and ALT by the investigator, and may
be assayed for yeast antibody at MSDRL. In addition,
participants who show an ant1-HBs titer ~ 25 mIU/ml
wi 11 have their seru111 tested to determine the
proportions of anti-! and anti-~ activity.
251&1/3
1/7/86
00374
Study 811

10 mcg Lot ,f974/C-K446 at 0, 1, and 6 months
1. Nul'llber Vaccinated:
Iniection No.
_1_ __2_ __3_
11 8 8
Serology data are available for seven part1c1pants
at 7/8 months. Eighty-six percent (6/7) of the
subjects seroconverted for anti-HBs (S/N :!:2.1) at
that t;me, Eighty-three percent (5/6) developed
protective levels of anti-HBs (mIU/111 ::10). The
GMT at 7/8 110nths for all vaccinees was 275.1
1111U/ml and 1076.6 mIU/ml for responders with a
titer of mlU/ml ~10.
Among subjects with serology data available at 12
110nths, 83% (5/6) were positive for antt-HBs
(mIU/ml ~10). The G'4T at that time was 44.1
111IU/ml for all vaccinees and 324.9 mlU/ml for
responders w;th a titer of mIU/1111 ~10.
Refer to Table l for ant1-HBs responses and GMTs
through 12 months of follow-up.
six participants after each injection. The
overall frequencies of complaints are presented
below.
Type of Frequency in% by In1ection No.

Complaint __,_ 2 3
Inject ion 0(0/7) 0(0/7) 0(0/6)

Site
Systemic 28( 2/7) 0(0/7) 17 ( 1/6)
25161/4
1 /7/86
00315
Study 811
RESULTS (CONT.): L1stings of spec1f1c clinical complaints are not

presently ava1 lable. There have been no reports
of serious or alarming reactions attributable to
vaccine.
25161/5
1/7/86
00376
Table 1.
Antibody Responses Among Health Care Personnel

Following Vaccination with 10 mcg Injections of Yeast Recombinant
Hepatitis B Vaccine Lot# 974/C-K446 at 0, l, and 6 onths
1n Study 811
% ( Proport 1on)
"11th Anti-HBs GlllT {mlUtmll
Tinie All ReSl!Onders
("1onths) S/N ? 2 .1 mIU/1111 ~ 10 Vaccinees S/N ~ 2. 1 mIU/ml ~ 10
1 0 (0/9) 0 (0/9) 0.3
3 38 (3/8) 38 (3/8) 2.4 77 .5 77.5
6 38 (3/8) 25 (2/8) 2.2 63.1 225.0

7/8 86 (6/7) 83 (5/6)* 275. 1* 1076.6* 1076.6*
12 83 (5/6) 83 ( 5/16) 44.l 324.9 324.9
* Based on 6 subjects (5 responders) for whom numeric titers are available.
25161/6
l /1/86
00317

Study 813
PURPOSE: To evaluate ant\body and cl1n1cal responses to several

dose levels of yeast recombinant hepatitis B vaccine
among the follo~ing populations:
1. Health Care Personnel (Seronegative)
2. Preimmune Adults

Lot 972/C--1(444 (10 IIIC9 HBsAg/ml)
Lot Bl9541/18071/C-l220 (10 mcg HBsAg/0.5 ml)
Lot 85860/22123/C-fll125 (20 mcg HBsAg/ml)
Lot 8586l/22124/C-flll26 (10 mcg HBsAg/ml)
PRINCIPAL Morton Davidson, H.D.

INVESTIGATOR: New York University Medical Center
University Hospital
560 First Avenue
New York, NY 10016
SECONDARY Saul Krugman, M.D.

INVESTIGATOR: Professor
Department of Pediatrics
550 First Avenue
New York, NY 10016
STUDY LOCATION: New York University Medical Center

University Hospital
560 First Avenue
New York, NY 10016
OATE INITIATED: February 1, 1984
DATE COfllPLETED: In progress.
2340I/l
1/18/86
00378
Study 813
STUDY POPULATIONS: Under the ori gi na l protoco 1 and subsequent addenda,

the following groups of health care personnel are
included 1n the study. Participants may be of either
sex, but pregnant women are excluded. ln1t1ally
seronegat1ve subjects have not previously received any
hepatitis B vaccine .
Addendiln l!o. Olaracteristics ~ V•cdne tot Ho. 11 Regiatn
lniti• l ln\t\al ly so 972/C-K«4 10 nq (1.0 111) at

protoa>I se~tive 0 , I , and 6 m:,nths
Add. , 1 Initially so 972/C-K«4 S 111eg {0.5 ml) at

seronegati ve O, 1, and 6 mnths
Add. f2 Initially so 972/c-u, 4 2.S nic:g (0.25 ml) •t

seronegallve 0, I, and 6 111011ths
Add . t13 Initli lly so 819541/18071/ 10 IIIC9 (0.5 1111) at

seronegative C-L220 O, 1, .rid 6 n,nths
Add. IC Initially so 8\9541/18071/ S mcg (0.2S 111) •t

seronegative C-L220 o, 1, and 6 months
Add. ,s Initially so 85860/22123/ 20 mcg ( 1.0 111) at

~tive; ~125 O, l, and 6 nonths
~ years of •ge
Add. #5 Initially so 85861/22124/ 10 ,neg (1.0 ml) at

seronegat i ve; ~\26 0, l, and 6 months
~40 years of age
Add. 16 Vaccinated 3-5 yrs 100 8586 \/22124i 10 IJIC:9 (1.0 ml) at
previously with C..ftl26 tillll! 0
pl .aaa derived
hepatitis B vaccine
(HEPTAVAX-8)
Add. 7 Vaccinated pre- 50 85861/2212'1 S acg (0.5 ml) !2!:

viousty t1ith C~ l26 10 11eg (1.0 •I) at
three 2.S Meg tilll! 0
doses of l'KC!llbi-
nant vaccine under
Add. 12.
23401-2
1/18/86
00379
Study 813
PROCEDURE: Participants receive intramuscular injections of

vaccine according to the regimens outlined above under
STUDY POPULATIONS. Those enrolled under addendum #5
who fail to develop antibody following 3 injections of
vaccine or have only a transient response that becomes
negative by 12 months after the first dose 11ay receive
a fourth injection of vaccine.
Participants wi 11 be asked to record their temperature

for 5 days after each injection of vaccine and to note
any local or systemic complatnts. Unexpected or
serious reactions are to be reported i11111ediately to
the study physician.
Blood samples will be obtained from the initially
seronegative groups prior to and on the day of the
first vaccination. Follow-up samples will be obtained
l, 2, 3, 6, 8, 12 and 24 months after the initial
injection of vaccine (initial protocol and addenda
# 1-5). Follow-up samples from persons vaccinated
under addendum #6 are only taken 1 month after
vaccination while persons enrolled under addendum #7
have blood samples taken 2 weeks, 4 weeks, and 6
months after vaccination.
Blood samples w111 be assayed for HBsAg, antt-HBc,
ant1-H8s and ALT by Dr. Krugman I s laboratory and raay
be assayed for yeast antibody by the Merck Sharp and
Dohme Research Laboratories. Samples with an anti-HBs
titer >25 mIU/ml may be tested to determine the
relat1ve proportions of anti-! and anti-& activity.

2.s mcg lot 972/C-K444 at 0, 1. and 6 months
5.0 mcg lot 972/C-K444 at 0, 1, and 6 months
5.0 mcg lot 1807I/C-L220 at 0, 1, and 6 months
10.0 mcg lot 972/C-K444 at 0, 1, and 6 months
10.0 mcg lot 18071/C-L220 at 0, 1, and 6 months
10.0 mcg lot 22124/C-f/1126 at 0, 1, and 6 110nths
20.0 mcg lot 22123/C-f/1125 at 0, 1, and 6 monts
23401-3
l /13/8&
00380
Study 813
RESULTS: l. Number Vaccinated:
Injection t4o .
Dose Level Lot ...L _2_ ...L
2.5 mcg C-K444 61 61 60 ( Addendu11 #2)
5.0 mcg C-K444 60 59 58 ( Addendum #1)
5.0 mcg C-L220 61 61 57 ( Addendum #4)
10.0 mcg C-K444 62 59 53 (Initial Protocol)
10.0 mcg C-L220 62 62 56 (Addendum #3)
10.0 mcg C-M126 1 3 -- ( Addendum #5)
20.0 mcg C~125 7 4 -- (Addendum #5)
Seven/eight month serologic data are available for
40, 43, and 36 participants in the 2.5 mcg, 5 11eg,
and 10 mcg dose regimens, respectively. Anti-HBs
responses at that time are sunniarized below:
Gm' (IIIU/al)
Dose 1, with Anti-Has All Resoonden
Level SIN ~2.1 mIU/inl ~10 Vaccinns S/~ ~2.1 111IU/11l ~10
2.s mcg 100 (40/40) 91 (39/40) 291.S 291.S 321.5

S mcg 98 (W43) 95 (41/43) 523.8 625.1 693.9
10 mcg 100 (36/36) 100 (36/36) 1509.3 1509.3 1509.3
Serologic results are not presently available for

the 7 participants who have received 20 mcg
injections of vaccine.
Refer to Table 1 for ant1-HBs responses and GMTs,
by dose regimen, through 12 months of follow-up.
23401-4
1/13/86
00381
Study 813
RESULTS: (Contd) 3. Clinical Complaints

Clinical follow-up data are availabl e for at least
60, 78, 77 , and 2 part1c1pants after each injection
in the 2.5 mcg , 5 mcg, 10 mcg, and 20 mcg dose
regimens, respectively. The overall frequencies of
complaints are presented below
Type of Oose Freauencv in I bv In-1ection

Com11laint Level 1 2 3
Injection 2.5 mcg 21 (13/61) 12 ( 7/61) 5 (3/60)

site 5 mcg 22 (27/121) 11 ( 13/119) 12 (9/78)
10 mcg 30 ( 38/129) 15 ( 18/119) 17 (13/77)
20 mcg 0 (0/6} 0 (0/2)
Systemic 2 .s mcg 13 (8/61) 3 (2/61) 2 ( l /60)

5 mcg 17 (20/121) 13 (15/119) 6 ( 5/78)
10 mcg 16 (20/129) 11 (13/119) 5 (4/77)
20 mcg 17 ( 1/6) 50 (1/2)
Refer to Tables 2 through 5 for listings of specific

clinical complaints by injection and dose regimen.
Maximum temperature data are presented 1n Tables 6
through 9.
Reaction Possibly Related to Vaccine

A 23 year-old female developed prurittc hives on her
back and legs within 24 hours of receiving the first
10 mcg injection of vaccine lot t-L220. All SYflll>toms
resolved by day 4 post vaccination. The subject
received the second injection of vaccine and within 24
hours again developed hives on her back, ams and left
hand. All symptoms resolved by day 4 post vaccination.
She received the third injection of vaccine with no
evidence of hives. The subject's medical history is
significant for an allergy to contrast dye (developed
hives during adm1n1strat1on of dye for CAT scan). The
development of h1ves post injections one and -two i~
considered probably vaccine related.
23401-5
1 /13/86
00382
Study 813
PUBLICATIONS: Davidson Fil, Krug11111n S. lmmunogen1c1ty of recombinant

yeast hepatitis B vaccine. Lancet 19B5; 1:108-9.
0av1dson M, Krugman S. Recombinant yeast hepatitis B
vaccine: Side effects and irnmunogenicity compared
with plasma-derived hepatitis B vaccine. Submitted
for publication to Hepatitis Scientific Memoranda.
23401-6
1/13/86
~
Ant\body Responses lllnong ln\th11ly S.ronegative Me•lth C.re Personn.1 Following

VacclNtlon with 10, S, and 2.5 111eg Injections of Yeast Recnlnant Hepatitis B V•cclne
at 0, 1, and 6 l'IOnths ;n Study 813
10 IIICG S n:a 2.5 .:a

I 11ith Anti-Mis CfIT (■Ill/all 1, vi th Antl-Hlls GMT l11IU/■1l \ 111ith Anti..ffBs llff (111IU/m1)
Ti• All - - - ~ r s -- All ·--...Jlesponders---- All --- Respondl!rs -
Months S~2.1 111IU/1111~10 Vacctnees S/~2.1 •IUl• 1~10 S/~2.1 •IUllll?l0 Vaccinees S/~2.1 MIU/1111~10 S~2 . 1 111IU/llll~IO Vacclnees S/~2. 1 mIU/111~10
1 · 45(48/104) 24(25/104) 2.0 18.4 63.9 35(371105) 20(21/105) 1.3 18.3 59.B 2JC16/60) 15(9/60) 1.0 23.6 165.9
2 89(86/91) 72(10197) 24.9 0.7 70.9 85(84/99) 55(54199) 14 . 4 28.J 19.B 71(37152) 44 (23/52) 1.0 25.2 6S.0
3 92(81/95) 86(82/95) 56.S 89.1 108.1 92(93/101) 80(81/101) 30.9 46.0 63. J 86(48/56) 63(35/56) 11.0 33.3 63.2
6 91(89/92) 93(86/92) 95. J 116.2 129.2 93(94/101) 84(85/101) cs.a 6'.6 BS.O 86(49/57) 70(40/57) 17.2 32.1 46.9
119 100(36/36) 100(36/36) 1509.3 1509.3 1509.3 98(42/43) 95(41/43) 523.8 625. 7 693.9 100(40/40) 97(39/40) 291.S 291.5 321.5
12 96(43/45) 96(43/45) 313.S 433. 1 433. 1 98(56/SJ) 91(52/51) 212.S 239.0 326. 1 96(45/47) 87(41/47) 98.1 127 .0 172.3
0
0
23401-1
""a,
~
1/13/86
Table 2
PATIENT CUlJ,ll CLINICAL COltPLAINTS
R£C01111INANT HEPATITIS B VACCIHE
STUOY I 09lJ
TREATMENT
DOS£ 2.5 tlCG
PATJEHT CLASS: HEALTH CAIi£ PERSONHEl
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCUIEU I 61 PATIEHTSI - DOSE 1 I
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I Nllt18ER
CLINICAL
C0rtPUJNT5
l----------------------------------------------------------------------------1
I O I l I 2 I J I 4 I S I
WITH
IC011PUJNTS
••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l•••••••••••••••-•••••I••••••••••
I I I I I I I I
RUCTION, LOCAL IINJf:CT. SITf:) I 11 I 8 I 5 I Z I Z I 2 I I ll
I I 18.0lO I I n.i:!t I I a.2;0 I I J,J):I I I J.liO I I J.37.1 I I I U.3)0
-----------------------------------1----------
SOIIEHUS I 2
----------
l
-··--------1----------
I I O
----------1----------
o I O
----------1-----------
I l
J,llO I 1.6::0 I O.OlO I I O.OXI I O,OXI I I t.OY.I I I 4.,7.1
I I I
UHDEIIHUS I 9 7 4 I 2 Z I 2 I •
14.&iO I 11.s;o I 6.67.1 I I J.31.1 I J.J;(I I I J,JlO I I 14.87.1
I I I
ERYTHEMA IIIEDNESSI I 2 1 1 I 1 l I 1 I t
J.JiO I 1,6?.) C 1,61.1 I I l.6i0 I l.6?.I I I l.6Y.I I I J.JlO
I I I
N~Rtml . I 2 l 1 I 1 l I 1 I f
J.JiO I 1,6?.) C 1,6?.J I I l.6i0 t 1.6?.I I I 1.61.1 I I 3.JY.I
I I I
PRUIIITIS IJTCIIIHG I I O O l I O O I O I 1
I I o.o;,o I I D.OXI I C 1,6XI I I O.OXI I C 0.01.1 I I 0.0%1 I I 1.6:'.I
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
SYSTEHIC I o I :s I 2 I J I 1 I • I I a
I c 0,07.J I I ,.,:-.1 I I 3.JY.I I I 4.9i0 I I 4.9:'.I I I 6.6%1 I I I 13.JiO
-----------·----------------------------------------------------------------------------------------------------------------
I
MIOLE BODl/GEHERAl I 0 z 0 0 l l I I 3
o.or.1 I ,. JY.I I o.o:i.:, I 0.0;:1 I 1.61.1 ( 1.,1.1 I I t 4.9%1
I I
SWEATING I 0
1.01., I
a
O.IIY.I C •
o.oz, I
0
O.OY.I I
0
0.01.1
1 I
C 1.6;0 I
I
I c 1.67.1
1
I I
f'ATIGUE/WEAKNES9 I 0 2 0 0 1 0 I I J
1.ox, I J.JY.I C O.OY.I I 0.0;:1 I 1.61.1 C I.OX) I I I 4,'IY.I
I I
RESPIRATORY I 0
1.0;:1 I •. ,x,
0
I
2
3.37.I I
1
1.oY.I I
1
1.6;(1 (
2
l.37.1 I
I
I
I t
I c J.Ji!I
I
RHINITIS I 0 I 1 I 0 0 1 I I l Cl
I O.OXI ( 1,010 I 1,6:iO I C 0.0:i.:1 I 0.0;:1 ( l.6iO I I t 1.67.J 0
""
~
b
....
Table 2 (cont)
PATIENT COUil CLINICAL COl1PLAJHTS
RECot1B INAHT HEPATITIS B VACCltlE
STUOY 1113
TRUTitENT
DOSI!: 2 • S t1CG
PATIENT CLASS HEALTH CaRE PERsot&IEL
I TOTAL VACCINEES I 61 PUUHlSl - 00,[ l I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I tu1BER
ClitlICAL
C011PLAIHTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I l I 4 I 5 I
NllH
ICot1PLUMTS
••••••••••••••••••••••••••••••••••• I••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
I
UPPER RESPIR AlOIIY I NFECT . , NOi I 0 0 1 1 1 l 1
I I 0.07.1 ( I .OY.I I l .67.I C 1.67.1 I 1.67.1 ( 1.67. 1 ( 1.61.J
I
tv.11:UlMK(UTAL I Q 0 0 1 1 1 l
0.07.I ( 0.0)0 ( o.o:o ( 1.67.1 ( 1.67.1 C l .6Y.I C 1.61.I
.-istLE STIFFNESS I II 0 0 1 l l l
o.o:o ( ,. 01.1 ( 0.07.1 t 1.67.1 ( 1.67.1 I 1.67.1 ( 1 .67.I
DIGESTIV£ S'r.lTEH I 0 1 0 l 0 1 ]
0.07.1 ( 1.61. 1 ( 0 , 01.I I 1.67.l ( 0.11)0 ( 1.67.1 C 4.97.1
DIARRHEA I O I O I O I O I O I l I I I
0.117.1 I I 1 .07.1I I O.OlO I I t.07.JI I O.OlO I I 1 .67.1 I I I l. l,7.1
I I I I I I I
NAUSE A I o I o I O I l I O I l I I 2
O. D7.I I I O.D7.I I I D.OlO I I l.6l0 I I O.DY.I I I 1 .61.1 I I I J.J7.I
I I I I I I I
V011JTING I Cl I o I o I 1 I II I O I I 1
0.07.J I( O.OY.I I( 0.0)!1 II l.67.1 I I o.o;o I I O.D?.I I II l.l,Y.I
I I I I I I I
DlHINISlfED APPETITE I O I 1 I O I O I o I O I I 1
I 1 0.0?.1 I , 1.,1., I r o.o;o I 1 0.01.1 I r 0.01.1 I r o.nr.1 I I < l.6lO
-----------------------------------1----------1----------l----------
PERSONs NITH C011PUINTS I 11 I 10 I 7
l----------1-------·-•l···-···---l----------f-----------
I S I s I 6 I t 20
I I 111.07.1 I ( 16 . 47.t I I Jl.57.1 I I e.2;0 I C 8 . 27.1 I I ,.e;o I I ( 32.87.1
-----------------------------------l----------1
PERSOffs 111TH NO COHPI.AINTS I 50 I
----------1
51 I
----------1
Sit I
----------I----------I----------I----------
56 I 56 I SS I
I-----------
I 41
I , e2.ox1 I 1 8J.67.I I c ea.s:o I , ,1.1x1 I , n .a%1 I , 90.2:1.1 I I , 61.2x,
-----------------------------------l----------l----------l----------l
P£Rs0ffs MITH NO DATA I D I O I O I
----------l----------1----------I----------
O I O I O I
I-----------
I 0
I I O. OlO I l 0.07.> I t o.o:o I I 0.07.1 I C o.o:o I l t. Ol!I I I c o.ox1
O ·
0
1,4
OD
Ill
-
Table 2 (cont)
PATIEm COIMT CLINICAL COHPUIIU9
AECOtl!IIIANT HEPATITIS B VACCINE
sn111, oeu
TAUTt1ENT
DOSE 2. 5 ffl:G
PATI£NT CUSS HULTN CAAi!. PERSONNEL
-- -- ------- ------------------------------------------------------------------------------------------------
I TOTAL YACCIN£ES l I
61 PATIEHTSI - DOSE 2
1----------------------------------------------------------------------------I
• DAYS POST VACCINATION I NU118EA
CLINICAL
COttPlAINTS
•-------------•--------------------------------------------------------------1
•
I
0
, •
I
1 I
I
, 2 I
•
3 •
•
4
,
I
I
5 I
I I
, MllN
................................... .......... ........•••.......... .......... ..........•.......... .....•.... ICOHPLAJNTS
.......... , ,
AUCTION, LOCAL CIHJECT . SITU • 5 I J I J I l I l I I I I 7
• l 9.tY.) I I ft.'JY.I I l .. . -.;o • l l . 6Y.I I I 1.1>7.) I I o.o;o I I I u.s:o
----------------------------------- __________ ,__________ , __________ ---------- ---------- ----------1----------1-----------
SOAENESS t I l I o o o o I I z
I J.llO I I l .6Y.I I I o.o;o l o.o;o l 0.07.1 I O.OY.I I I t :S.JY.I
I I I I
UND£AH£SS 3 I 2 I 2 0 0 O I I ft
I 4.9l!I I I J.3:'.I I l J.l:1.1 I O. o:o I o . o::o I O.OY.I I • I 6.6l0
I I I I
EATTHEMA IAEDNE!l9 1 l I l I O O O O • I l
I 1.6)!1f I 1 .6)0 • I 0.0l!I I o.o;o I o.o;o f o.o;o • I I 1 . 6,0
I I I •
PRURITIS IITCHIHGI O I O • l 1 l O I I l
I o.o;o I I o.o;o I t 1.f>Y.I l 1.6:t.l I J.f>7.I l 0 . 0i!I • I C 1.6)!1
-----------------------------------l----------l----------•----------l----------•----------•----------l----------
s,sret11c I l I O I 1 I 1 I D I O I
l-----------
I 2
I I l.6)0 I I 0.0)0 • I l.6%1 I I 1.6Y.I I I o.o;o I t o.o:o f I ( l.3i!l
----------------------------------------------------------------------------------------------------------------------------
I
WlfOU BOOUGENEAAl l O I I O O O I l
( 1.u:1 C o.o;o I I.IY.I I l D.OY.I I o.o;o C o.o;o I l 1.6)!1
I I
HEADACHE 1 0 0 I O O O I l
C 1.6)!) I O.OY.I C D.OY.I I I ,.or., I O.0l!I I o.or.1 I I 1 .6?.I
I I
A[!IPIAA.TOll'f O o l I 1 o O I l
I O.OXI I I .OY.I I J .6l!I I I 1.6:0 C 0.0Y.I C I . DY.I I I 1. 6Y.I
I I
AHINITl9 0 t O I 1 I O I l
I 0 . 07.1 C I.OX) I o.o,o I I l.61.I I 1.1;0 C o.o;o I l l .6i0
I I
N!IEtzts o o t I o , o I 1
I o.o;o t o.o:o I 1.6)0 I l 0.01.1 I o.or.1 I 0 .0iO I I I 1 .67.1
-----------------------------------1----------l----------1
PlllsONS WITH COttPLAIHTS I • I J I ----------I----------I----------I----------I----------I-----------
~ I z I 1 I o I I 9 0
:::,
I I 'J.9>:I I I ft.9:'.I I I 6.67.1 I I 3.JY.J • I 1.6?.I I I o.o;o I I I l4.8i0 ~
!JD
O'-
Table 2 (cont)
AEC0118INANT HEPATITIS 8 VACCIHE
STUDY 0813
TREATHEHT
DOSE 2.5 IICG
PATIENT CLASS HEALTH CARE PEASotlHEL
I TOTAL VACCINEES < 61 PATIENTSI • DOSE 2 I

Il----------------------------------------------------------------------------1
DAYS POST VACCINATION I t!Ul18EA
CLINICAL
COt1PUIN'fS
1•·-•---•---•-•-•-••--••--•--------------------•-----------------------·••·••f
I o I l I 2 I 'J I 4 I 5 I
WITH
ICDt1PlUNt!I
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••••••••••••••••••••••••I••••••••••
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsONS NlTff 110 cOHPuINTS I ss I 58 I 57 I s, I 60 I u I I sz
I 1 •0.21.1 I , 95.l:O I , n."1., I , 96.n, I 1 '9&.":o I 1100.0:0 I I I es.21.1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------1-·---------
PERSONS WITH HO OAU I o I o I o 1 o I o I o I I o
I I o.o:o I I 0.1:;o I C 0.01.1 I I o.o;o I I 0.07.1 I I 0.07.1 I I I o.o:o
0
0
v,f
Ot
"-4
Table 2 (cont)
PATIENT COIMT CLINICAL COMPLAINTS
REcottBIHANT HEPATITIS 9 VACCINE
STUOY oeu
TREA Ttt[HT I
OOSE 2. 'S ttCG
PATIENT CLASS: HEAlffl CARE PERSONffl:L
---·------------------------------------------------------------------------------------------------------------------------
I TOTAL VAccmus I 60 PATIENTS) - DOSE 3 I
l----------------------------------------------------------------------------1
I bAYS POST VACCJNATIOlf I t1Ut1BER
CLINICAL
Cot1PLAINTS
1------------------------·--··--------·-------·----------··------·-----------I
I I I 1 I Z I J I 41 I 5 I
WITH
ltOMPUltlTS
·································••l••·················••
I I Il••M·····••l••·······•
I Il••······••l••······••l••······••l••D·•·····
I I I
REACTION , LOCAL UNJECT. snu I l I O I I I O I • I O I I 3
I 1 5.0lO I I o.o;o I c 0 . 11:1.1 I c 0 . 0:1.1 I c o.o:o I c o.o:o I I c s .o:o
-----------------------------------l----------l----------l----------
uNDuNEss I 3 I O I O
l-----·-···1----------1----------1----------1-·---·-----
I II I I I D I I 3
I I S.OY.l I I O.lllO I C I.DY.I I I O.OY.I I I O.OZI I I o.o:o I I I s.o:o
-------- .--------------------------l----------l----------l----------
s un111c I O I O I O
l----------1
I l I
----------l----------t----------l-----------
1 I 1 I I l
I I o.o:o I I o.o;o I C O.OY.I I I 1 .7:1. 1 I I 1.71.1 I I J .71.J I I I 1.71.J
-~--------------------------------------------------------------------------------------------------------------------------
1 I 1 I I I I I
IIESPil!ATORY I o I O I O I l I 1 I 1 I I 1
I I O.OiO I C o. or., I t o.or.1 I I 1 .1;0 I t 1,77.1 I I 1 ,77. 1 I I I 1 . 7)( 1
I I I I I I I I
UPPER IIUPil!ATORY INFECT., NOS I O I O I O I 1 I 1 I O I I l
I I 0 . 07.1 I I 11.DiO I C 0.07.1 I I l.7%1 I t 1.7Y.I I I o.o;o I I I l.7i0
1 I I I I I I I
COUGH I 0 1 DI O I ol ol ll I l
II O. o;o II O. a;o It O. or., II O• ox I I I e. 0)0 I I 1 . 71.1 I II 1 . 7r. l
-----------------------------------1---------- I----------I---------- I----------I---------- I----------I----------I-----------
PEIISOIIS WITH COf1PlAIHT9 I 3 I a I o I 1 I l I 1 I I ~
I t s. oin I I a. a:1.1 I , o. oz I I t 1 • T/.1 I 1 1. T/.1 I , 1 . 1:1.1 I I t 6. 11.1
-----------------------------------l----------
PERSotlS WITH HO COHPLAIHTS I 57
l----------l----------
I 60 I 611
l----------1----------1----------1·---------I-----------
f §9 I 59 I 59 I I 56
I , ,s . or.1 I nao.o;o I 1100.0:1.1 I 1 9&. 1z1 I , n . 1:1.1 I 1 .a . 1:1.1 I I c n . 17.1
-----------------------------------1----------l----------l----------l----------l----------l----------1----·-----
PER!OtlS WITH NO DATA I O I D I O I O I O I O I
I-----------
I D
I C 0.01.1 I I 0.07. 1 I I ,.or., I I t .O:'. I I C 0 . 07.1 I I o.or.1 I I I o . o:o
0
0
~
,:,,
OD
·-
Table 3
PATIENT COUNT ClINICAl COttPlAIHTS
RtCOttBINANT HEPATITIS 8 YACCJtl(
STUOY t 11813
TIIEATl1ENT :
DOSE I 5 HCS
PATI ENT CLASS: HEALTH CARE PERSONH£l
I lOlAl VACCJNEES C 121 PATilHTS) - DOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST VACCJHATIOH I NUMBER
CLINICAL
COl1PUINTS
l----------------------------------------------------------------------------1
I O I 1 I Z I 3 I 4 I 5 I
WITH
ICot1PLAINT9
•••a••••••••••••••••••••••••••••••• ••••••••••• l••••••••••••••••••••• l•••••••••• ••••••••••• r••••••••••• •••••••••• I••••••••••
I I I I I I I I
RUCTION, LOCAL IINJECT . SITl! I I 22 I lt I 4 I 1 I o I o I I 27
I I 111.2x1 I C ,.,xi I I S.3?.I I I 0.11;0 I I o.or., I I o , o;n I I I 22 . ]XI
-----------------------------------1----------
INFLAnt1ATION I 1
----------
1
----------
D
----------
o ----------
o ----------
o ---------- -----------
I
I I 0.11?.I I O.IIXI I O.OY.I ( o.o;o C o.or., I o.ox, I O. IIXI
I
PU N- I 2 I O o o o 2
I I 1.7)0 C O.IIXI I o.o:o ( o . o:o I 0.1%) I o . o:n I 1 .7?.I
I
!IOIIIENUS I 1'4 II 3 l I O 17
I I U.6l(I ( 6. 6l0 I z.SXI I O.IIXI I o.or.1 I o . o:o I l<t.OXI
I
TEHIIERNESS I 6 3 0 0 0 O 7
I ( . s.o:o C z.Sl(J I o.ox, I O.OXI ( o.ox, I o.oi , I 5.IIXI
I
STlFFHUS/TIGHTNESS I O 1 0 0 0 0 l .
I I o . or. 1 C • • ,;,; , I 0.0)0 I a.ox, ( O. OXI I I O.OXI I o.e:o
I I I
PIIURITIS UTCHlNGI I 1 l l O O I O I 2
I C D.IIXI C , .ex, I O,IIX I C o.ox, C o.ar., I I o.o,o I I 1.7)(1
I I I I
ECCHYHOSIS I O l l 1 I a I O I 1
I I o.a;i1 c I c o.11r.1 I I a.ax, I , o. o;o
1.ex1 I I o . e:o I I o.er. 1
----------------------------------- 1----------1----------I---------- I----------I----------I---------- I----------I-----------
SYSTEHI C I 14 I 9 I 6 I 4 I 4 I 3 I I 20
I I Jl.67.1 I I 7.4l0 I I 5.0XI I I 3.3XI I C 3 . 3:o I I z.s:o I I I 16.SY.I
-----------------------------------------------------------------------------------------------.
I I I I I I ----------------------------
I I
MHDLE IIOOY/GEHIEAAL I 9 I 4 I 4 I J I 3 I J I I 13
I r 7 . <tlO I I J.3l0 I C 3.3?.I I I t.s;,:1 I 1 2 . 57. 1 I r z.s:o I I I 10 . 71.I
I I I I I I I I
FEYER ITEMP . NDT REPDIITEDI I 1 I l I 0 I D I D I 0 I I l
I I 0.11%1 I C O.IIXI I I o . or. 1 I c O.OY.I I I o.or.1 I, e . oY.I I I t o . er.1
I I I I I I I I
SWEA UNG I
I I
l
o.117.1 I I
I 0 I
o.o;o I c
0
0.0.r.1
' •
I C II.DY.I I I
I 0 I
0 , 07.1 I f
0
O.OXI
I
I
I
I I
l
0.81.1
0
0
vi
OD
..0
Table 3 (cont)
PATltHT COUHT CLINICAL COttPlAIHTS
AECOt19JNANT HEPATITIS B VACCINE
STUOY OBll
TRUTl'IEITT
DOSE 5 HCG
PATIENT CLASS HEALTII CARE PERSOHNEL
-------------~--------------------------------------------------------
I ·-----------------------------------------------------
TOTAL VAt'CJH[ES I 121 PATIEIITS I - DOSE 1 I
1-------
I
··-------------------------------------------------------------------1
DAYS POST VACClNATIOfl M.lt18ER I
CLlHICAl
Cot1PlAINTS I 0 I 1 I 2 I 3 I ,. I 5 I
1----------------------------------------------------------------------------I NITH
ICot1PUIHT9
•••••••*•••••••••••••••••••••••••••l••••••••••I•--••••••• •••••••••• •••••••••••~••••••••• •••••••••• e•••••••••l••a•••••••
I I I I
FLUStl I 1 I 0 I D I D 0 I 1
D.8)!J I ( 0 .DY.I I 0.1)!1 I o.or.1 I , O.OXI
FATIGUE/WtlkHESS I 6
I
I z l 2
I
I z
' a.ox•
2
I I
I
0.8XI
9
S.07.1 I I 1. 71.1 ( 2.57.1 I l. ?Y.I ( 1. 7Y.I ( l. 7XI ( 7 . 47.J
I
t1AUISE 3 I 2 l 0 0 0 ,.
( 2.SY.I ( 1. 77.1 I 0.87.1 I O.OY.I ( I.DY.I ( 0.0)!1 I J.:s:n
HEADACHE 2 l 1 l l 1 4
( 1. 77.1 ( o.s::o I o.e:1.1 I D.BiO ( t.87.1 I I O.BY.I I l.J:r.l
UGHTHUOEO
(
l
0.8i0 I
D
D. 07.J ( •
0.07.1 (
D
0.01.I (
0
1.07.1 (
0
o.o:o I
1
0.117.J
RlSPIRATOIIY 3 5 1 z 2 l 5
I 2.57.1 I 2.s::o C a.BY.I I 1. 7Y.) I 1.77.1 ( 0.8)0 I ,. _17.J
PffAAYHGITts I SOl!E TIIIIOAT I l t l z l l ]

( 0.87.) ( 1.r,o ( 0.87.1 I l. 77.1 C ,.ex, ( 0.(11.1 I 2.s:o
I
UPPER RESPIRATORY INFECT., NOS I 2 t l l l 0 2
.I I 1. 77.1 I 1.7:0 ( 0.(17.) I D,8Y.I ( O.IIY.1 ( a.07.I ( l. 77.1
I
WHEEZES I 1 0 0 0 0 0 l
I I 0 .111.1 I 0.0::t.l I o.o:o I o.o:o C 1.0:'.I ( 0.07.1 I 0.87.1
I
11USCU LOSIC El[T Al I t J 1 0 0 a ]
I I 1. 77.) ( i!.57.1 ( o.e:r.1 I 0 . 0Y.I I 1.0:f.l I O.OY.I I 2.57.1
I
ARTHSUTIS, 11CNOAIITICUUR I l 1 l 0 0 0 l
o.e:o I 1 o.v., ( o.a:o I D,01.1 C t.OiO ( 0.07.1 ( 0.87.1
II ' I
ARTIIRAlGIA, HONOARTICULAR I l I 1 l D 0 0 l
t.87.J I I 1.e:r.1 ( 0.87.1 I 0.07.1 C 11.07.1 ( 0.07.I I 0.8:1.1 0
I 0
~
AR"Tlll!ALGIA COTHERI I l I l 0 0 D a l -0
C o.ex1 I 1 o.ox·1 I 0.07.J I II.DY.I I 11.07.1 O.OY.I
' I o.e:o 0
Table 3 (cont)
REC0r181NANT HEPATITIS B VACCIUE
STUDY Ollll
TREATMENT
DOSE 5 tlCG
PATIENT CLASS HEALTH CAIIIE PERSOW!t!L
I TOTAL VACCIHEES I lZl PATIEMTSI - DOSE l I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NIJHBER
CLINICAL
COl1PUINTS 1----------------------------------------------------------------------------I
I O I 1 I 2 I 3 I ~ I 5 I UITH
IC011PLAINT5
•a••••••••••••••••••••••••a••••••••••••••••••••••••••••••l•••••••••••••••••••-•l••••••••••••••••u•••••••••••••••••••n••••••
I I I I I I I I
BACI< PAIN I O I l I O I o I o I o I I 1
11 . 0:1.1 I 1 1.11:0I I o.o:o I I o.o:o I r o.o:o I 1 11.0:0 I I 1 0.117.1
I I I I I I I
OTHER I 1 I 1 I o· I o I o I o I I 1
0.11:0 I I o.aio I , 0 . 01.1 I I o.o:o I I e.o:o I , o.o:o I I , o.ar.1
I I I I I I I
DIGESTIVE SYSTEt'I I Z I O I t I D I O I O I I 2
1.nl I c o.ox1 I I 0.01.1 I I o.o:o I 1 0.0;!1 I I e.o;o I I 1 1.n,
NAU!IEA l I
o . ar.1 I I
0 I
o.o;o I 1
0
0.01.1
I
II
0
o.o:o I r
I 0
0.01.1
I
II
0
a.or., I
I 'II I
1
0 . 8 1. )
I I I I I I I
ABDot'IEH DISTENDED 1 I 0 I 0 I 0 I 0 I 0 I I 1
D.IIY.I I I O.Ol() I( o.o;o I1 0.0;!1 I I o.o:o II 0.01.1 I I t O,IIY.1
I I I I I I I
NERVOUS SYSTEt'I 0 I 1 I 1 I 0 I 0 I 0 I I 1
0 . 01.1 I ( 0.117.l I I 0.117.1 I I o.o:o I I o. o:o I I o.o:o I I c o.a:o
I I I I I I I
VERTIGO/DIZZINESS
I
0
O.OY.I
I
I I
1
D.81.)
I
It
1
0.11:0
I
I I
0 I
o.o;o I 1
0
O. OY.I
I
I I •
,.or.,
I
I
I l
I ' O.IIY.I
PSYCHIATRIC/l!EHAVIORAL I O I O I l I 1 I l I 1 I I 1
1.or.1 I , 1.01.1 I c o.e:o I 1 0.11:0 I I o.11r.1 I 1 •.ar.1 I I , o . 11r.1
I I I I I I I
IRR IT A81LIT"f I O I O I 1 I I I l I 1 I I l
I I ,.or., I I o.o;o I I o.a:o I I 0.117.1 I I o.e:o I I O.lli(I I I I 0.IIY.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I------- ----
PERSOHS MITH COt'IPLAlHTS I 34 I 20 I 9 I 5 I II I 3 I I 41
I I H.17.) I I 16.SiO I I 7.11:0 I I tt.1:0 I I 3.3:O I I t.s:,o I I I l.J. 9;!1
--·--------------------------------1----------I----------I----------I----------I----------I----------I----------I----------·
PEl!SOtlS NlTH HO COl1PLAINTS I 117 I 101 I 112 I 116 I 117 I 118 I I 80
I I 71.'IY.I I I 83.5:o I I 9t.6Y.J I I 95.9Y.I I I 96.7iO I I 97.5;!1 I I I t.6.lZI
-----------------------------------1· ---------l---------- l---------·1---------- l----------l----·-----I----------I-----------
PERSOHS MITH HO DATA I I I I I D I o I O I O I I O
I I I.DY.I I I 0.0:() I C 0.0?.I I I o.o:o I I o. o;o I I 11.0;0 I I I 0.0Y.) 0
c:,
u-1
-
,0
Table 3 (cont)
PATIENT COUlfT CLINICAL C0!1PLAIHTS
RECot18INAHT H£PATITl9 B VACCINE
STUDT 0811
Tl!EATNElfT
DOSE 5 nc:G
PATIENT CLASS HEALTH CARE PEASOHHEL
- --------- ---------------------·--------------------------------------------·-------------------------------------------
I TOTAL VACCINEES I 120 PATIENTSJ - DOSE 2 I
l----------------------------------------------------------------------------1
I DAYS POST VACClllATIOM I lrut18ER
CLINICAL
CotlPU.lNTS
1--------------------------------------------------·---·---------------------I
I O I l I Z I J I 4 I 5 I
WITH
ltot1PUJHT5
••••••m•e••••••••••••••••• .. ••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••f•••••••••al•••~•••••••••a••••M••
I I I I I I I I
REACTION, LOCAL (INJECT. SITEI I 11 I 5 I l I l I l I l I I U
I I 9.2)0 I I ,.z::o I I l.!5:t.) I I 0.87.) I I 0.8)(1 I I 0.87.1 I I I 10.9)0
-----------------------------------1---------·
PAIH I 1
----------1----------1----------
O I o I o ----------1----------1----------1-----------
o I o I I 1
o.e:t.1 1 o.o;o I • I
0.0:t.1 c o.o:o • o.o;oI 1 I
0.0:1.1 I 1 11.e:1.1
I I I I I
SIJIUNESS I 8 , I J I O 0 I II I I 11
6. T/.t < 1 •.-.,0 I t 2.s:o I , a.oz, , o.o:o I 1 0.01.1 1 I , ,. 1;0
I I I I I
TENDERHESS I 2 0 I 0 I 1 l I 1 I I J
1. n1 I 0.07.J I I 1.07.1 I t 0,87.1 I o.8)(1 I ( o.ez1 I I I z.s:o
I I I I I
l&IEAL/WIIUL AND PURE I O l I O I o O I II I I 1
I , 0.0:t.1 1 0.11:t.1 I « ,.o:o I I o.o;o c o.o::o I c o.or.1 I I 1 11.11r.1
-----------------------------------1----------l----------t----------l----------l----------l----------l----------l-----------
snnKit I :S I II I 7 I , I 3 I :S I I 15
I I z.s:o I I 6.7)(1 I I S.9:0 I I J.4)(1 I I 2.5?.I I I 2.s::o I I I 12.6::0
WHOLE BODY/GENERAL
I
I 2 , l 1 I z 2 I 9
I I 1. 7:t.l I t.57.1 ( 0.8i0 I o.e:o I 1 1.7)() I 1.1;0 I I 7.6:1.1
I I I
FEVER CTENP. NOT REPOl!TEDI I II 0 0 1 I 1 l I l
I c o.o;o I 0.07.) I 0,01.I ( O.IIY.I I I o.e;o C O.IIY.J I I a.e:o
I I
FLUSH I Cl 0 0 0 1 0 I 1
I c 0.111.J ( 0.01.1 ( O.OY.I I 0.07.1 o.~, o.11Y.1 I
' o.ax 1
( I
t I
SENSATION OF WARNTH, «;€HERAL I 0 1 0 0 l 0 I z
I c o. 01.J I 1.8)0 I O.OY.I I 0.07.1 ( 0.11)0 I o.oY.1 I ( 1. 7)0
I I
FATIGU£/WEAkHESS I 1 l 0 I 1 2 I 4
I c 0.117.1 ( 0.8)() C 0.01.1 O.&lO o.e:o I I
HALAISE
I
I 0 0 0
' 0
I
0
1.11.1
I
I
I
I J.4i0
1 0
I c O.OXJ I 0.0)0 I o.o:o I ,.or.1 ( o.oz' I o.a:t.1 I I o.e:o 0
\>I
,0
N
.
,.,
Table 3 (cont)
PATIEHT COUNT CLINICAL CONPUIHTS
RECOMIIIHANT HEPATITIS 8 VlCC111£
STUl>T G8ll
Tl!EATt1£NT
DOSE S l'ICG
PATl£NT CLASS HEALTM CME PERSOtlN(l
----- -- ---- ---------------------------------------------~----------------------------------------------------------

I TOTAL VlCCIN[[S f lZO PATIEHTSI - DOSE Z I
l----------------------------------------------------------------------------1
I DAYS POST VlCCllfATION I N'Utll!ER
CLINICAL
COt1PLAINTS
1----------------------------------------------------------------------------I
I O I 1 I 2 I J I 4 I !I I
WITH
IC011PlAIHTS
~•~•••••a••••••••••••••••••••••••••l•••••••••••*••w••••••I•••••••••• ••••••••••I•••••••••• •••••••••••••••••••••f~••bvww••~
I I I I I
HEADACHE I 11 11 1 al o 01 ]
I I 0.8%1 I I 0.811 I I 0,811 I D.0ZI I I O.OXI I a.Oil I I !.5%1
I I I I I
ll[SPlRATOR'I' OI JI 4 11 D 11 5
f o.o:;o I ( 1.5)0 I I J.411 I l.8XI I ( O.OZI I 0.8:t.1 f I 4.2%1
PHARYNGITIS (SORE TffROATI 0 2 3 o
I
I o 1
I
I ,.
O.OY.I 1. 7Y.I Z.5ZI l a.ax, I l a.ox, I 0.8ZI I ].411
I I
UPPER IIESPIIIATORY INFECT., NOS 0 2 z o I o o I 2
a.0Y.I l.710 1.7ZI I 0.0ZI l I O.OXI l O,OZI I l. 7i!I
I I
OTHER 0 1 1 l I o I I
I D.0Y.I , o.e:o I O.IIY.I o.ez, I I o.ox, I 8.t:t.l I I 0.11:t.>
I
Ht"IC AND LYttPIIATIC 1 11 21 Z t ll 3
D.8ZI o.8:o I , 1.1:1.1 I 1 1.1:0 , 1.1:0 1 o.eY.1 I I 2 .SY.I
I
LYHPHADENOPATHY, CENEIIAL 1 1 J l 2 l I !
D.8)O o,9;0 0.8)0 D.8XI f 1. 7Y.I I 11.tZI I 1. 7Y. I
I
lYttPHADENOPAYHY, CERVICAL a 0 1 1 o II I l
o.o:o I 0.011 I t.8i0 0.811 , o.o;o 1 ,.o.r.1 I 0 .11:1.1
I
OIGESTIVE !IY!ITEN 0 2 0 a o o I 2
, o.o;o I 1.T/.1 t.OY.I o.oz1 , o.o;o , 0.01.1 I 1.7i!I
I
IIIAlmHEA al 11 ol O o OI l
, ,.oi:1I , I « o.o;o I ,
O.a;(J 0.0;:1 , o.oi:1 , 1.01.1 I I O.IIY.)
I I I I
NAUSEA •I ti tit o ol I z
( o.o:o I I l.7Y.I I l o.tY.I I ( 0.0%1 ( o.0Y.I I I
t.0Y.I I I l.7iO
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WltH CCfflllAINTS I n I U I 9 I 4 1 J I 3 I I Z4
I I 10.'>XI I I 10.111 I I 7.6:CI I I J.4%1 I I 2.5%1 I l z.s;o I I I 20.2%1
-----------------------------------1----------1----------I----------I----------I----------I----------I----------I----------- 0
PEIISOHS WUM HO Cet1PUJHT5 I 106 I 1117 I llD I US I 116 I 116 I I 9S 0
V,
I I 99.llO I I 89.97.1 I I t2.u:1 I I 96.r.;o I I '7.S%1 I I 97.SY.I I I I 7'1.lllO ..0
1,1
•
Table 3 (cont)
PATIENT COUNT CLINIC AL COl1PLAJNTS
RECOH81NAHT HEPATITIS B VACCINE
STUDY Ollll
ffl EATt1EHT
DOSE S l'ICG
PATI ENT CLASS: HEALTII CARE PlRSOHNE L
I TOTAL VACCJNEES I 120 PATIEHTS I - DOSE 2 •

•----------------------------------------------------------------------------
• DA'tS POST VACCINATI0N 1I MUl18tR
CLINICAL •------------------------------------------------------- -------------- ------ -• WITH
COffl'L AIHTS I O I 1 • 2 • J I " I S I I COHPLAINTS
~••••••••••••••••••••• ..•••••••••••••••••••••• l••••••••••l••••••••••••••••••••••••••••••••l ••••••••••••••••••••• l•••n••••••
-·---------------------------------l----------l----------
P£RSOIIS WITH NO OATA I 0 I 0
l----------•----------l----------l----------l----------1-----------
• 0 I 0 • o • 0 • I o
• C o.o;o I I 0.0)0 I I o.o:o I ( 0.0)0 I I O.OY.I I C 0 .0:!I • I I o.o;o
0
0
.....
,0
~
Table J (cont)
PATIENT COUNT CLINICAL COt1PLAIN15

R[Cot1BJNAHT HEPATITIS B VACCINE
STUDY 01113
TREAffltHT
DOSE S "CG
I TOTAL VACCINEES I 115 PATIENTS! - DOSE l I

1----------------------------------------------------------------------------I
I DATS POST VACCINIITlON I NUNBER
CLINICAL
COHPLAJNT!J
1----------------------------------------------------------------------------I
I O I 1 I t I 3 I 4 I 5 I
WITH
ICONPLAIHTS
•a~•••••••••••••••u•••••••••~e•• .. ••••••••••••l••••••••••l••••••••••••••••••••~l••••••••••l•••••••••••••••••••••I••••"•••••
I I I I I I I I
IIUCTIOtl, lOCll IINJECT. SITl:I I II I J I l I l I II I o I I 'I
I I 10.3?.I I I J.11:O I I 1.J?.I I I 1.37.1 I ( O.D?.I I I 0.0)0 I I I 11,57.J
-----------------------------------1----------1----------l----------t----------1----------l----------l----------l-----------
s011tHESS I 2 I 1 I O I o I o I o I I z
I I 2.61.1 I I 1.3)() I I 0 . D:'.I I I o.o:o I I 0.0?.I I I 0.0?.I I I I :!.6Y.I
I I I I I I I I
lENDEIINESS I S I 1 I l I 1 I O I O I I 6
I I 6.4)(1 I I l.])() I C 1.31.1 I I 1.37.1 I ( o.,;o I C 0.07.1 I I I 7.71.1
I I I I I I I I
PRUIIITIS I JTCHINGI t 1 I 1 I 0 I 0 I 0 I 0 I I 1
I t 1,31.1 I I 1.:SXI I I 0.0Y.I I C 0.0Y.I I C 0.0Y.I I I 0.0Y.I I I C l.lY.I
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sysnttic I z I 1 I o I o I e I o I I 5
I I Z.6Y.I I I ].II)() I I D.07.J I I a.oz, I I 0.tXI f I 0.07.1 I I C 6.4XI
I II I
~OLE BODY/GENERAL
I
1
1. 3:!I (
]
J.IIXI I
0
0.0Y.J C
0
0.07.1 ( 11.0Y.I I
0
o.o,., I ( "
5.lXI
FATIGllE/WEAKNESS I 0
0.0:!I (
z
2 .6Y.I (
0
o.o:o (
0
o.o,., ( ...,.,
e
'
0
0.0Y.I
I
I
(
z.
Z.6XI
NAUISE I 0
O.0XI (
1
l .:SY.I
0
o.o:o C
D
0.0:!I
•
•• ,1.1 (
0
0.0Y.I (
1
1 .3?.I
' C
HEADACHE I 1
1.31.1 C
2
l!.6)(1 C
0
o.o:o (
0
O.0ZI ( •
0.0)0 I
0
0.0)(1 I
l
3.11?.I
II '
ACIUHESS I 0 1 0 0 0 0 l
I O.0Y.I I l.JXI ( 0.OY.I o.o;o ( o.o;o I o.or., I I. JXI
I
I
'
H[HJC lltlll LYHl'HATJC I
I I
l
1.])(I C
0
0.0Y.t
I
I I
0
0.0Y.I C
•
o.o;o C
D
o.o;o I
0
o.o:o I
1
n.1;0
I I
LYHPHADl:NOPATHY, GUll:RAL I
I I
1
1.JY.I (
0
I.DY.I
I
I I
0
o.o:o (
•
0.01.1 (
•
o.oin I
0
o.o;o I
l
ll..lY.I
0
0
IA
,.,,0
-
Table 3 (cont)
PATIEHT COUNT CLINlCAL COMPLAIHTS
IUC0t18INAHT HEPATITIS II YACCJtlE
STVDT 01113
Tl!EATH£NT
DOS£ 5 t1CG
PATI ENT CLASS Ht AlTl4 C~I PIRSctM l
I TOTAL VACCIHf:ES C 115 PATifNTSI - DOS£ l I

1----------------------------------------------------------------------------I
I DAYS POST VACttNATION I N\Jl18ER
CLINl CAL
COMPLAINTS
1----------------------------------------------------------------------------I
I o I 1 I 2 I 3 I 4 I 5 I WITH
ICDNPLAJNTS
"••••••••••••••••••••••••••••--•••• l•••••-•••• 1•••••••••• •••••~••••• 1••••••••••1•••••••••• 1-••••••••• l••••••••••l•~o•••••••
-----------------------------------1----------I----------I----------I----------I----------I----------
PUSOHS WITH COMPLAIHTS I 9 I 6 I l I l I O I O
I----------I-----------
I I 13
I I 11,57.1 I I 7.7Y.I I I 1.3%1 I I l.lY.1 I I o. o:o I c o . o:o I I c 16.7XI
-----------------------------------l----------
PUSONS MITH NO COt1PLAIHTS • I 69
l----------l----------t----------1----------1----------1----------I-----------
I 72 I 77 I 77 I 78 I 711 I f 65
I C 88.s;o I C 92.]Y.I I I '18.7½1 I I 911.77.1 I U00 . 0%1 I flOD.o;o I I C ll] . ]:11
-----------------------------------1----------l----------l----------l
PEIISOH!I Wint NO DATA I O I O I O I
----------l
O I
----------1----------
O I O
I----------I-----------
I I 0
I I O. OXI I I O.OY.I I I 0.07.1 I C O.OY.I I I o .o:o I I O.OY.I I I I 0 . 0:11
Q
0
""0-
-0
-
Table 4
PATIENT COUNT CLINICAL COf1PlAIHTS
RECOttlllHANT HEPATITIS B VACCIHC
STUOJ 0111]
TRUTlttNT
DOSE 10 ltCG
PAlIEHT CLASS HEALTH CARE PERSONNEL
--------------·-------------------------------------------------------------------------------------------------------------
I TOTAL VACCIN££S I 1)2 PATIEHTSI - DOSE l I
l----------------------------------------------------------------------------1
I DAYS POST VACCitlATJOH I NU11BER
CLINICAL
t0t1PLAIHTS
1----------------------------------------------------------------------------I
I O I 1 I Z • 3 I 4 • 5 I
YITH
•cot1PUINTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••I••••••••••
RtACTiffi, LOCAL CINJECT. SITE I
t
I 27
II 17
•I ID
II 3
II t
II 2
II II 311
I 1 20.<11.1 I , u.2::1 I , 1.11;0 • , 2.J1.1 I 1 1.6,0 I 1 1.ii!1 I I I n.s?.1
-----------------------------------1----------l----------1-··--------1----------l----------•----------•----------I-----------
PAIN I t I l I 1 I o I o I o I I :S
f I 1.6)0 I I 0.11)0 I I tl.lli!I • I O.Oi!I • I o.o;o I I 0.01.1I I I t.li!l
• I I • I I • I
SORENESS I n I 7 I 4 • 2 I l • l I I 18
I ( U.lXI I I S.ft)(l f I 3.llO I I l.6l0 I I 0.111.1 f I ,.e;o I I I l't.li!I
TENDERNESS I 11 I 7 I 4 I 0 I 0 0 I I 15
I I 11.Si!I I I S.'ti!I I I 1.1::'.I I I 0.01.1 I I 0.0::'.I I• I o.o:o I f I U.61.I
I I I I I
• I
ERYTHEMA IREDHtSSI I l I 0 I 0 I 0 I 0 I 0 •
I 1
I t 0.117.1 I I O.OXI I I 0.0,:1 I I 0.0,:1 I I o.o;n I 1 0.0:1.1 • •I I 0.11:0
I I I I I I I I
!CCHJMOSIS I 0 I l I 0 I 0 I 0 I 0 I I 1
O.OXI I I o.a:o I , o.e,:1 • c o.o;o • I 0.0,:1 I c 0.01.1 I • I 0.111.1
RASH, NOS I l I l I t I l I 1 I l • I 1
I I O.IIXI I I 0.117.J I I 0.8?.I I I 0.11:0 I I 0.111.I I I 0.111.I I I I O.lliO
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sysrErtlC I 10 I 11 I II I 6 I 3 I 3 I I 20
I I 7.117.) I f e.SX) I I 6.ZY.I I I ... 77.1 I ( t.JiO I I Z.lY.) I I ( 1s.s;1.1
----------------------------------------------------------------------------------------·-----------------------------------
I I
WHOLE BODY/GENERAL I !; l t I 1 I l I I 8
]. 91.1 ( 2.ll!I I 1.61.1 o.e:o f I I
I
' ( O.IIXI
I
0.11:0
I I'
I
f>.ZXI
FEVER CTEl'tP. NOT REPOIITED I 0
O.OlO C
2
1.6)0 I
D
0.01.1
0
0.07.1 f
• I
I
0 I
I
I
I
z
FATIGUE/NEAKNESS I 3 1 0
' 0
o.ox1
1 I
I
c O.D1.1
1
I
I
I
I
I l.6Y.I
4
2,31.1 I O.IIXI I O.GlO ( O.JY.I ( 1.11:0 I 1 O.IIXI I I I l,li!I
I I I
11AlAISf I l
o.a,o t •
I.OY.I C
1
0.8)() C •
0.07.1 I
0 I
o.o:o I I
0
O.OlO
I
I
I
I I
z
l.6ll
0
0
"'.....a
Table 4 (cont)
PATIENT COUNT CllNtCll Cot1PUitlTS
RECOt19INANT HEPAT1Tl9 8 VACCINE
ST\JOY I oen
TREATMENT :
DOSE 10 t1CG
PATIENT CLASS• HEALTH CARE PERSOHH[l
--------------------------------------------------------------------------------------------------------------------
I TOTAL YACCINEES I llt PATIENTS! - DOSE l I
1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I tl\Jt113ER
Cllt«CAL
Cot1Pll INTS 1----------------------------------------------------------------------------I
I 0 I l I 2 I J I I 5 I ~
WITH
ICotlPUINTS
ua•••••••••N•w•••••••••••••••••••••I•••••••••• ••••••••••l•••••••••• ••••••••••I•••••••••• ••••••••••fa•••••o•••I••••••••••
I I I I I
HEADACHE I 1 0 I l 1 I 0 D I I 2
8.81.1
• D.Ol!l II I 0.8Y.l ' o.e;o II c o.o:o ' D.D:!I II I ' 1,6)(1
I
IN1ECTIOIJS SYHOROl1E9 I 0 1 I l
o.az1 I c 0.8Y.I
0 I 0 II I I l
0.81.l ( I I.DY.I I I D.OXI o.o:o I I c o.8:!I
INFLUENZA, HOS 0 l
I
I 1 0
I
I 0
' II II I
I l
o.o:o
' o.eio I c
• o.9r.1 I o.o;o
( I c O.OY.l o. oz, I I I D.1!7.1
INTE;Ul1EHTART SYSTEn l t l l 0 D J
( o.e;o • 1.6%1 ( o.ez, I o.9z1 t O.Oi'!I I o.o:o
' 2 .]1.1
UIITICARI&lfflVES 0 1 1 1 0 D 1
t D.117.1
l'RlmlTIS/JTCHIN& II
' o.&Y.1
l
' 0.8%1
0
'
0.8%1
0
' O.OXI
0
I
I
( I.Dl!I
D
( 0.1!7.I
1
( O.Ol!I 0.8Y.I t t I ,
' O.OY.I o.or.1
( 0 .OXI 0.07.1 ( 0 .Iii()
PASH, HOS
I
l 0 0 II 0 0 l
I 0.8)(1 I O.DY.I I O.Ol!I o.o:o 0.0;(1
' o.o:o (
RESPIRATORY I 1 2 2
' 2 2 2
' 0 . 87.1
!I
I I 0.87.1 ( 1.6;() I l.61.1 1.1.:1.1 1.67.) l.6;(1
' ] . '97.1
(
IIHIHITIS
I
I D 0 l
' 1
' 1 0 2
o.o;n
II '
I o.o;o I 0.87.) ( 0.117.1
• 0.87.l ( O.OY.I l l.67.1
PHARYHGITIS I SOf!E THROAT I I 0 l 2 1 t 1 ]
0.07.1 ( 0.117.) I 1.67.I I o.e:f.l I 1.67.1 I 0.117.1 ( t. 37.1
I
UPPER RESPIIIATOIIY INFECT., HOS I l I l 0 0 0 1 J
11.8)(1 I I 11.11)0 0.07.1 I I
ttEnit AND lYlfflHlTIC I 0
I
I 0
' 0
0.07.1
l
' 11.117.1
0
' O.l!Y.I
0
2 . 37.1
1
O.OY.I I I o.o:o ( 0 . 0)0 ( o.er.1 II.DY.I 0.07.1
lYl1PIIADENOPATffY, CERVICAL I 0
I
I 0 0 l
' II
' 0 I
'
o,9;0
1
0
.,.
0
o. 07.1 I 1 0.07.) I
( 1.e:r.1 I 0.11:0
' O.DY.I I O.DY.I
' D. eY.J
"'
(lD
6
Table 4 (cont)
PATIENT COIJIT CLJHICAL COMPLAINTS
RECONeIIUNT HEPATITIS B VACCIIIE
Slut)Y 0813
TREAT11ENT
0OSE 10 ttCG
PATIENT CLASS HEALTH CARE PERSON11£L
I TOTAL VACCINEES I 132 PATIENTS) - DOSE 1 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I tll.JHBER
CLINICAL 1----------------------------------------------------------------------------I WllH
COIIPlA IHfll I I 1 I 2 I 3 I I I ICOMPLAJHTS
0 5
"
•~a••Dauaa••••••••~u••••••••••••••• •••••••••• •••••••••• •••••••••••~•••••••••••a•••••••••••••••• ••••a••~••l••~••••••o
111.JSCULO!IK ElET AL l l 0 0 0 0 1
I 0.111.1 I o.a:o I 0.07.1 I o.o::o ( o.o:o ( 0.0)(I ( 0.11)()
NECK STIFFNESS 1 l 0 0 0 0 l
( 0.87.l ( e.11:O ( 0.0)() ( 0.07.I I o.o;o I 0.0)() I 0.8)()
DIGESTIVE SYSTEN J 2 1 D 0 0 5
2.37.1 ( l.6l0 I 0.111.t I o.o:o I o.o:o o . o;o J.9)(1
' '
(
ABDOl1IHAL PAINS/CRAtlPS 0 J 0 D 0 0 l
0.0)0 ( 0.87.1 I o.o:o I 0. 07.l I 0.0iO I 0.0)(1 I 0.8Y.I
DIARRHEA I 1 1 l 0 0 0 2
o.e:o I o.a:o ( 0.87.1 ( 0 .01.1 I 0.07.1 I I 0.0)0 I 1.67.1
I
NAUSEA I 2 0 0 0 0 I 0 2
1 .67.1 I 0.07.1 ( 0.0Y.l ( 0.DXI I o.o::o I t o.o::o I 1.67.1
I
VOl1ITING I 0
o.o:o I
1
0.87.1 (
D
o.o;o C
0
0.07.1 I
0
0.DiO
' C
0
O.Oi'.I I
l
D.117.l
OTH[II 0 1 1 D 0 0 l
( o.o;o ( 0.81.J ( o.a;o I O.Oi!I I o.o;o I O.OiO I 0.8i0
UROGENITAL SYSTEn 0 l 1 1 1 1 2
D.0::0 0.87.) 0.8)0 D.8:o 0.87.1
' ' I I 8.87.1
( 1.67.I
' (
UIIJHAIH TRACT JNflECTION

I
0
0.0Y.l I •
o.o:o I
D
0.07.) I
l
0.8)(1 I
D
0.07.) I
0
0.0:r.1 (
l
o.a:o
DYSURIA 0 J 1 0 0 0 l
I 0.07.1 I 0.8)!) ( o.a;o I 0,DiO I ,.ox, I 0.01.l ( 0.11:r.1
OTHIER 0 0 0 0 1 l l
0.07.1 I I 0.07.l I 0.0:r.1 r 0.0lO I t.8)0 I 0,IIY.I C t.87.t
I 0
0
Ol!GANS OF SJ'ECIAL SENSE I l I 0 0 0 0 0 1 \,a
0.117.1 I I o.or.1 I 0.DXI ( 0.0:r.1
• ,.ox, ( 0.07.I ( o.11r.1 .a
,0
--
Table 4 (cont)
PATIENT coun CLINICAL Cot1PLA1NTS
AECot181NAHT HEPATITIS II VACCIIIE
STUDT aeu
TIIEATl1£NT
OOSE 10 t1CG
PATIENT CLASS HEALTH CARE 1'£RSOMfEl
I TOTAL VACCINEES C lU PATIENTS I - DOSE l I

l---------~------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I NUMIIEA
CLINICAL
COMPUIHTS
1·------------·--·-··------------------------··----------------·-------------I
I o I I I 2 I J I 4 I 5 I
WITH
IC011PlA1HTS
dM•••••••••••••••••••••••••••••••••&••••••••••l•••••••-••l•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••o•••••
I I I I I I I I
l!LURl!ED VISION I l I O I o I o I O I O I I 1
f I D.117.1 I ( 11.0i(I I I 0.01.1 I I 0.0:1.1 I I o.o:o I I 0.07.I I I C 0.!17.1
-----------------------------------l----------l----------l----------l----------l----------1----------I----------I-----------
P£RSONS MITH COttPlAlNTS I lt I Z6 I 17 I 9 I '5 I S I I 49
I C 24.11%) I I 21.tr.l I I 13.t?.I I I 7.o:o I I J.9Y.I I I ].9Y.I I I C 311.0)0
-----------------------------------1--------··1···-----·-1·------··-l----------l---···-·--1----------I----------I-----------
PER!OMS MITH HO COMPUINTS I 97 I 103 I llZ I 120 I 124 I lZct I I 110
I I 1s.2r.1 I I 79.e:o I I 86.81.1 I I 9J.0iO I I 96.lY.I I I 96.liO I I I 6:Z.07.1
-----------------------------------1----------l···-------1-··-····-·1----------1--·-------l----------l----------1-----------
PERSON!I WITH HO DATA I O I O I II I O I O I D I I 0
I C o.o;o I I o.or.1 I I 0.01.1 I I I.DY.I I I 0.01.1 I I o.o;o I I I 0.0Y.I
0
0
t::
0
0
.,
Table 4 (cont)
PATIENT COUNT CllNlCAl COHPlAlHlS
11£Cot1BINAHT HEPAlITIS 8 VACCIIIE
STUDT 0613
TIIEATMENl
DOSE 10 ttCG
PATIENT ClASS HlALlH CAR£ P£11SDNHEL
---------·------------------------------------------------------------------------------------------------------------------
I TOTAL YACCIHEES I 125 PATIEHTSI - DOS£ t I
1----------------------------------------------------------------------------I
I OAlS POST VACC1NAT100 I NUf13EII
CLINICAL
COltPLAINT!I
l----------------------------------------------------------------------------1
I o I 1 I 2 I 3 I 4 I S I
WITH
ltOttPLAlNTS
a•••••••••~••a•••••••••••••••••••••l••••••••••••••••••••••••••••••••l••••••••••••••~•••••••••••••••••I•••••~•••••••••••••~•
I I I I I I I I
REACTION, LOCAL I INJ!CT. SITE I I 13 I 10 I 7 I 2 I 1 I 1 I I 'lll
I I 10,9)(1 I I 8.4lO I I 5,9)(1 I I l. 7?.I I I o.ex, I I 0,87.) I I I IS.l?.I
-----------------------------------1----------
PAIN I 1
----------l----------1----------1----------1----------
2 I l I l I o I o ---------- -----------
3
o.a:o I l.7:11 I I 0,8)(1 I I 0.8%1 I I 0.07.1 I I 0,0lO I t.s;o
I I I I
S011£HE5!1 I 5 • I 3 I l I l I 1 6
4.t?.I 1 3.4?.I I 1 2 . sx1 I I o.a?.1 I I t.87.1 I , o.ax, , s.o;o
I I I I
TEtllJEIINESS I 7 • I J I o I o I o 9
5.9¼1 I 3.4:11 I I 2.SY.I I I 0.0Y.I I l 0.Oi!I I ( o.0?.I I 7.6lO
I I I I
STIPFNESS/TIGHTNESS I 2 l I 0 I 0 I 0 I 0 2
I I l. 7X I I 0. 8%) I t 0. 07. J I I O. o:o I I O. OX I I I O, 07.1 I I. 7i( I
-----------------------------------l----------t----------l----------l----------t----------l----------l----------l-----------
s,sun1c I 5 I , I 7 I 5 I 6 I r, I I n
I I 4.2Y.I I I 7,6)() I I 5,97.1 I I 4.27.1 I I 5,0iO I I 5.07.1 I I C J0,97.1
W'HOL£ BODY '6ENEAAL I 3 s 3 I t 2 t 8

2.57.1 I •.t?.I I 2.5)(1 I l. 7?. I I 1.7?.I C I. 77.1 ,.no
FATIGUE/WEAKNESS I 3 2 1 2 2 2
' 5
I t.5?.I I 1.7;(1 I D.87.1 C l.77.1 I l. 77.1 C I. n:, ( •.ZY.I
t1AlAlSE 0 I 1 I 1 I 3
I 0.0)0 I 0.8)0 I 0.8:1!) I o.e:o o.8XI I l,8lO I 2.57.)
HEADACHE 0 z I 0
' 0 0 t
I 0.0)() 1.7)0 O.OiO o.o:o o.o:;o
lNTEGUnEHTART STSTEH 0
I
I
' 1
I 0.8?.I
z
C
2
I
l
I
1
I I. 7Y.)
2
I 0.D7.I I I 0.8)0 I 1. 7%1 ( 1. 77.1 ( 0.8:1!1 I 0.87.1 I 1.7)0
I
URTICARIA/HIVES 0 I 1 l I 0 0 1 0
I 0.0,:1 I I 0.8)() I 0.87.) 0.87.1 o.o:o I D.0X) 0.117.l
'
C ( 0
&:
....
0
•
Table 4 (cont)
PATIENT COtR-IT CLINICAL COHPLAJNTS
RECOttBINANT HEPATITIS l'l VACCJIIE
STUDY 0813
lREAlHEHT
DOSE I 10 l'ICG
PATIENT CLASS: KEALTH CARE P£ASOte!El
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIIIEES I HS PA TilHTS l - DOSE 2 l
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUMBEA
CllNICAl
CONPLAINfS
1----------------------------------------------··----·---------·-------------I
I O I l I 2 I :S I It I 5 I
MITH
IC011PLAINTS
•e••••••••-••••••••••••••••••"•••••l•••••~••••l•••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••a•••••••
I I I I I I I I
PAUIIITIS/JTCNUIC I a I a I 1 I 1 I 1 I 1 I I 1
a.oz, I C O.OY.J I I 0.8Y.I I I 0.11:0 I I 0.11%1 I I 0.11:0 I I I 0.87.1
IIE!IPIIIATORY l t l t I
I 0.87.1 I l. T/.1 I 0,8)(1 C l.7i!I I " "
3 ...Y.l I C 'J.4Y.I I
5
4.27.1
I
PIIARYNGITIS ISORE THAOATI l t 1 l 2 I 2 3
( 0.81.l ( 1. ?XI I 0 .1'1)0 I 0.8)(1 I l. Tl.I I C 1.7?.I I 2.5%1
I
LARYNGITIS 0 0 a a l I l l
I O.OiO I o.o~n I 0,DiO I O.DY.l I O.IIXI I C o.e:o I 0,87.l
I
UPPER RESPIRATORY INFECT., HOS 0 0 D 0 l I l 1
I o.a:o I o.o:o 0.07.1 C o.ei(I I f
BROHCHITI!I, H09 0 0
' 0
11.0XI
D
f
l
I
0.8Y.I
1
I 11 .8% 1
1
I O.D7.I C O.Oi(I I O. OXI O.OXI I
COUGH I 0 0 0 I
' 1
I o.a:o
a
o.ex,
0
I 11.l'li()
l
I I 0.07.) C O.OY.I I 0,0?.I I I 0.8i0 O.DlO I O.lllO C
NEHIC AND LYHPHATIC

I
a I
I ' 0.117.1
••I I 0.0?.t
0
o.o:o I
1
o . ei(t I r
0 0 0 l
I ' I
0.07.1
' O.Oi(I I 11.or.1 I 11.87.1
l'r11PICADEHOPATHY • GENERAL I
I I
0
0.07.t C
a
0.07.1
1
0.8?.)
I
f
•
,.ox,
0
C o.oxt I
0
11.07.1
l
0.87.1
LYNPICAOEt«>PllllY, CERVICAL
I
I D
' (
G l II I II 0 l
Ir
I
0.0lO
,- C 0.0?.I I 0.87.I ( 0.07.I I C O.Ol!I
I
I 11.0XI
' 0.87.1
NUSCULOSKELETAL I
IC
0
o.ox1
I l
I « a.ext I
0
0.07.J (
0 I
I.DY.I I I
D
O.Oi(I •
1.07.1
1
0.8)()
HYALGIA
I
I 0
I
I l 0 0
I
I 0
I
I
' 0
' l
o.a,o I , 0.1'1?.I C 0.07.1 ( O.OXI I l 0.01.1 I , 0.07.1 C 11.87.1 c:>
I I I Q
OI;£STIY£ SYSTE" I l I 0 0 a I 0 I II 1 b
0.87.1 I c 0.07.1 C 0.07.1 I. OY. I I I 0.07.1 I I O.OY.I c:,
' I 0 . 87.1
ru
·-
-------
· Table 4 (cont)
PATIENT COIJHT CllHICl l tOl1PLAIHTS
REC0111UH&Hf HEPlflTI!I & vaccme
STUDY 0813
TR£ All1EHT
DOSE 10 HCG
PATIENT CLAS, HEALTH CAIi! PlA!ONNEl
I TOTAL VACCIHEES I US PATIEHTSI - DOSE Z I

l----------------------------------------------------------------------------1
I DAYS POST YACCIHl TIOO I NUt18EII
CLINIC AL
Cotff'll lHTS
1I ---------------------------·-··-·-·-------------------·---------------------I
O I I I 2 I 3 I <t I 5 I
WITH
ICOtlPLAIHlS
• 0 •a•••••~••••••••••••••••••••••••• l•••••••••• l••••••••••••••••••••• l•••••••••• •••••••••••l •••••••••• l••••••••••I••••••••••
I I I I I I I I
A8DOl1JNAL PAINYCRA11PS I 1 I O I o I o I O I o I I l
I ( o.e;o I I O.DZI I I o.o;n I I 0.0:1.1 I I O.OZI I I O. OZI I I I o.e;n
I I I I I I I I
DIARRHEA I l I O I O I O I o I o I I I
I I o.ez1 I ( o.OZI I I O.OZI I ( O.OZI I I ,.oz, I I O.OZI I I I O.IIZI
-----------------------------------1·---------l----------
PERSOHS WITH COttPlllHTS I 16 I 16
l-··-------l----------1----------l·
I 14 I 7 I 7 I
----------1
7 I
----------I-----------
I 27
I I n.4Zl I I 13.47.1 I I 11.e;o I I 5.91.I I I 5 . 9)0 I I 5.9Zl I I I u . 77.1
-----------------------------------1-···------l----------l--------·-1----------l----------l----------l----------
PERSONS WITH HO COltPUIHTS I l Ol I 103 I 105 I 112 I 112 I JU I
l---·--------
I 92
I t 116.67. 1 I I 116.621 I I ee.2z1 I I '14. 11.l I I 94 . lZI I I 94.llO I I I 77 . ]Z)
-----------------------------------l------·-·-1···-·-····1----------l----------1----------1----------1----------I-. ---------
PERSOMS WITH NO DATA I I I O I O I o I O I I I I 0
I ' 0.0ZI I I o.o:;o I I o.o;n I I O.OZI I I 0 . DlO I I O. 0ZI I I I o.oz,
-::,
0
C
0
u,I
_..,
Table 4 (cont)
PATIENT CO\MT tlIHICAL COMPlllHTS
REC0111!INANT HEPATITIS B VACCINE
STUOY HU
TR£ATN£NT
DOSE 10 HCG
I TOTAL YACCIHUS I 1119 PATUNTS I - DOSE J I

1----------------------------------------------------------------------------I
I DA1S POST YACCINATIOH I NU118ER
CLINICAL
COl1PlAttns
1----------------------------------------------------------------------------I
I O I 1 I :t I J I 41 I 5 I
WITH
ICOl'IPUIHTS
••••••••••••••••••••••• .. ••••••••••••~••••••••l••••••••••l••••••••••••••••••••••••••••••~•l••••••••••l••••••••••••••Q••••••
I I I I I I I I
IIIEACTIOH, LOCAL IIHJECT. SITE> I 11 I 10 I 6 I 6 I 5 I s I I U
I C 14.JY.I f" I 13.0lO I C 7.e;o I I 7.e;:1 I I 6.57.1 I I 6.S:o I I I 16.9%1
-----------------------------------1----------l----------l----------l----------l----------l----------1----------I-----------
PAlH I l I 1 I 1 I o I o I e I I I
I.Jr.I I I 1.JXI I C l,JY.I I I O.OXI I I 0.0;:1 I I 0,07.1 I I I 1.37.1
I I I I I I I
!IOl!EHESS I e I 6 I J I l I :t I t I I 9
10.4;:1 I c 1.e;:1 I C J.97.l I I J.9;:J I I :t.6i0 I C t.6%1 I I I ll.7XI
I I I I I I I
TEHDEl!HESS I 2 I t I l I l I l I 1 I I l
t.6Y.I I I :t.67.I I C 1.JXI I I l.lXI I C 1.J7.J I I 1.3;:J I I I J.9%1
[RYTHENA CR[DNESSl l 1 l 1 o I o t
I 1.37.1 l,JlO 1. 3%1 1.liO o.ox1 I I o.ox, 2.6%1
INIJURATION I O I 1 I l I l I l I 1 I I l
c o. ox I I I 1. 37.1 I I 1. JiO I I l. Ji! I I I l. 3i0 I I 1. 37. I I I I 1, l7. I
I I I I I I I
PAPULU s I I O I 1 I l I 1 I l I l I I 1
O.OlO I I 1.17.l I I l.l%t I C 1.Ji!I I C l.J%1 I I 1,3%1 I I I l.JiO
I I I I I I I
STIFFNESS/TIGHTNESS I l I l I l I 1 I l I 1 I I 1
I C 1.31.1 I C 1.37.1 I C l.37.1 I I 1.1;:1 I C 1.JXI I I 1.31.1 I I I 1.]%1
-----------------------------------l----------l----------l----------l----------l----------l----------l---------l-----------
srsnn1c I l I t I t I l I l I o I I 1t
I I_ 1.37.I I C t.f>7.I I C t.f>i'-1 I l l.UI I C l.JXI I I O,OiO I I t 5.2%1
I I I I I I I I
I
WHOLE BODY/GENERAL I
II '
l
J. 3?.I
I t
'
2 I
I C Z.6?.t I I Z.6%1 I I
l I
1.37.1 I I
l I
1.37.1 I I
0
O.OXI I '
f I
4
5.;!XI
NALAI5E I 0
I I a. ox1
I
I 1 I '
0
I
I
I c 1.JXI I I 0.0%) I I
0
o.o:o I I
I
I •
I
I
0.0;:1 I I
0
I
I
0,0;,:1 I
I
I
I I
l
l. ]%1
I I I I I I I I
HEADACHE I 0 I 1 I 2 I 1 I 1 I a I I 2
0
I C 0.0;:1 I 1 l.J;:J I C t.6i0 I I 1.3%1 I C 1.l)O I I 0.0?.I I I c t.61.t 0
b
0
.t:
....
Table 4 (cont)
PATIENT COUCT CLJNJC AL COMPLAINTS
l![COHBitlAllT HEPATITIS B VACCINE
STUOY 081]
TRUTl1EHT I
DOSE 10 MCG
PATIENT CLASS: HE ALTH CARE PERSOtNL
I TOU L VACCINEES I 109 PATIENTS I - OOSE l I

II ------.. · · --------- . . · --· ·--------- -·--· --· ·· ··-·· ---·····---------····----·-II
DAYS POST VACCIHATIOO H\JttBER
CLINIC AL
COl1PLAINT9 I
1-----------------------------------------------------------------------·----f
o I l I t I 3 I c; I s I
MITH
ICOHP\AlHTS
a•••••••••••••••••••••••••••••••••• t•••••••••• l•••••••••• l••••••••••••••••••••• ••••••••••• l•••••••••• l•••••••••• I••••••••~~
I I I I I I I I
ACHINESS I l I D I D I o I o I 0 I I l
I I 1.JXI I I O.DXI I C o.ox, I I o.o;o I C o.o;o I I o.o:o I I I 1.37.1
-----------------------------------1--------·-1----------
PHSONS MITH COHPUINTS I 1t I U
1I ----------1·---------l-------·--1----------l----------1-·------·--
1 I ft I 6 I s I I 15
I I 15.f,7.) I I 15.6X I I I 9.17.1 I I 7.8Y.I I I 7.e:o I C ,.s:o I I I n .sr.,
--------------------------·--------1--···-----l-·---·-···1-------·--1----------l----------l--------·-1----------I-----------
PERSOM9 MITH tl0 COttPLAIH'l'S I ftS I r,5 I 70 I 71 I 71 I 72 I I 62
I I e,.1tr.1 I c M.47.1 I c 911 . 9XJ I 1 92.2:r.1 I , u.2:i1 I c 9J.57.I I I I eo.sr.,
-----------------------------------l----------l----------l----------l----------l----------1--·--··-··1----------l----·------
PfRsOl1s MITH HO IIATA I O I O I O I O I O I I I I 0
I I o.o;o I I 0.0,0 I C ,.or., I I O.OXI I I O.D,O I I 0.07.) I I I O. Ol!I
0
0
C
0
\II
Table 5
PATIENT COl.l'IT CLINICAL COl1PLAJN1S
RECOHBINA>fl HEPATITIS B VACCINE
STUDT 081]
lR£All1f.HT
bOSE ZO 11CG
PATIENT CLASS HEALTH CARE PERSONH£L
I lOTAL VACCU1£ES l 7 PATIEIITSI - DOSE 1 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I N\1118£11
CLINICAL l----------------------------------------------------------------------------1 WITH
COHPLAINTS I D I 1 I t I J I 4 I 5 I ICOHPLAIHTS
•••a•••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••~••••••••••••••••••I••••••••~••••••••••••••••~••••••
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sTSTEHtC I 1 I o I o I D I o I o I I 1
I ( 16.7)0 I I I.DY.I I I 0.0)(1 I ( O.Ol!I I I O.OY.I I I o.o;o I I t Ut.7ll
-------------------------------------------------------------------
1 I I I I I
WHOLE BOOl/GENERAL I l I D I O I O I o I O I I 1
J6.r,o I I o.ox1 I I o.or.1 I , o.oio I , o.or.1 I , o.oio I I t J6.n1
I I I I I I I
SENSATION OF WAAltTH. CDIEAAL I 1 I O I O I O I o I a I I 1
I ( 16.7?.J I I O.OlO I I O.OiO I I o.o:o I I O.Ol!I I I D.Olll I I I U.7ll
----·------------------------------1----------l----------1----------I----------I----------I----------I----------I-----------
PERSONs lfllff COMPLAINTS I 1 I O I O I o I O I O I I 1
I ( 16. 7?.I I I O.OY.I I I O.OZI I I O.OY.I I I O.OY.I I I O.Olll I I f 16.7?.I
-----------------------------------1----------l----------1----------I----------I----------I----------I----------I-----------
PERSOHs MITH HO COMPLAINTS I S I 6 I 6 I 6 I 6 I 6 I I S
I C 8J.3)0 I 1100.0Y.J I 1100.0Y.I I 1100.0Y.I I 1100.0iO I ClOO.OY.I I I I 19J.])(J
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PH~s MUM HO DATA I o I o I o I o I O I O I I O
I , o.ox, I , o.an I 1 0.0,:1 I , a.ox, I , a.a;,o I , a.ox, I I I o.ox,
0
0
~
0
c,,
-
Table 5 (cont)
PATIENT COUNT CLINICAL COHPLAIHTS
l!ECOt18IMANT HEPATITIS 8 VACCIUE
STUDY I 0013
Tl!EATtt[HT
DOSE 20 11CG
PATIEHT CLASS• HEALTH CARE PEIISOH!fEl
I TOTAL VACCIMEES l 4 PATIEHTSI - DOSE 2 I

1----------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I MJN!IER
CLINICAL
Cot1PLAJtlT!I
1----------------------------------------------------------------------------I
I D I l I 2 I l I 4 I 5 I WITH
ICotlPlAIHTS
••e••••~•••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l•••••••••••••••••••••••••••••••••••a•••••••
-----------------------------------1----------1----------1----------l----------1----------l----------l----------l-----------
svsnHIC I O I I I 1 I 1 I 1 I 1 I I l
I ( o.o:o I l so.o;o · ' I !iD.OiO I I so.0;1.1 I I so.o;o I I SD.0%1 I I I 50.07.1
WHOLE BOOYIGEHEIIAL I 0 1 0 0 I 0 0 1
I < o.o;o I 50.07.I o.o:o I 0.01.1 I I o·.01.1 0.07.1 so.ox,
I
(
I '
SEHSATIOH OF NAIIHTII, GENERAL I 0 1 0 0 I 0 0 1
o.o:o ( 50.07.1 o.o,o 0.07.I II o.o:o I 0.0%1 I SO.DY.I
'
( (
I
fATIGUE/MlAKHESS I 0 l 0 0 I 0 0 1
0.07.1 ( 50.0%1 I 0.07.1 I 0.0%1 I I 0.0%1 I o.o;o 50.0%1
I
IIESPIRATOAY I 0 l 1 I I l 1 1
•• 07.1 ( ,o.o:o I 50,07.1 l SD.07.J II 50.07.1 ( S0.0%1 so.ox,
I
PHAIIYNGUIS I SOIIE THROAT I I 0 1 l l I 1 l 1
0.07.1 C 50.07.1 ( 50.07.1 I 50.0%1 II 50.0%1 ( so.oz, so.o:o
I
Of!GANS Of SPECIAL SENSE I 0 0 0 1 I 1 l 1
o.o;n ( 0.07.I 0.07.1 I 50.07.1 I I SD.0?.I I 50 . 07.1 I 50.07.I
'
(
I
EARACHE I O I O I o I l I 1 I l I I 1
I l 0.01.1 I I 0.07.1 I I 0.01.1 I < 50.07.1 I < so.01.1 I I so.o;o I I c so.or.I
-----------------------------------l----------t----------1----------l----------1----------1----------1----------1-----------
PERSOHS llllH COHPUIHTS I O I 1 I 1 I 1 I 1 I l I I 1
I c 0.01.1 I , so.01.1 I c so.o;o I , so.ox, I I so.o;o I I so.ox, I I c so.ox,
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH HO COl"IPLAIHTS I 2 I l I l I 1 I 1 I l I I 1
I 1100.0:r.1 I l so.o;o I C so.ox, I I so.or., I I so.ox, I I 50.0)(1 I I I 50.0%1
-----------------------------------l----------1-·--------1----------l----------l----------1----------1----------1-----------
PERSOHS WITH HO DATA I O I O I O I O I O I O I I O
I, o.ox1 I c o.oxt I, o.ox, I, o.or.1 I, o.or.1 I, o.ol!I I I I o.or.1
0
0
.c::
0
.....
•
Table b
PATIENT COUNT MAXIMUl1 TEMPER ATURES
RECOt1BlHAHT HEPATITIS 8 VACCitlE
STUDY 1 01113
TRE ATnEHT
DOSE 2 .5 ltC6
PATIENT CLASS! HEALTH CARE PfRSOffll£l
I TOTAL VACCIHEES I 61 PATIEHTSI - DOSE I I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCJNATJON I 11-\JNIIER
MAX TEMPERATURE
I DEG F, CRALi
1------------------------------------------------•--------------------------------------I
I t I 1 I 2 I l I " I 5 I I I MAX TEMP
MITH
••••••••••••••••••••••••••••••••••• l•••••••••• l•••••••••• ••••••••••• ••••••••••• l•••••••••• l•••••••••• l•••••••••• I••§•••••••
I I I I I I I I
HOIINAL I 60 I 59 I 60 I 60 I 60 I 59 f I 59
I ( 'J8 •• l0 I I 96 . 7Xt I I 911.47.t I I 98. 47.t I I 911 . 47.1 I I 911 . lZl I I I 96. 77.I
I I I I I I I I
< 99 I 1 I l I l I l I l I l I I l
I f l.6XI I I 1. 6Y.I I I l . 6XI I I 1. 6Xt I I 1.6%1 I I 1.77.t I I I 1 . 67. t
I I I I I I I I
99 - n.9 I o I l I o I D I o I D I I l
I I ,.or., I f 1.67.) I I 0.0%1 I I 0.0)0 I I 0.0)0 I I a.o:o I I I 1 . 67.)
------------------------l----------l----------l----------l----------
n:tff'ERATURt T AKEN I 61 1 n t n I u l----------l----------1---------------------1-----------
I 61 I 60 I I n
I ,100.or.1 I 1100 . or.1 I 1100.ox, I 1100.ox, I c100.ox1 I, 99 . 47.1 I I 1100 . oz ,
------------------------l----------l----------l----------l----------l----------l----------l---------------------1-----------
n l f tRAT\JRt HOT TAKEN I a I o I • I o I o I 1 I I a
I I , .or., I C o.ax, I I •• ,x, I I o.oz, I I D.OXI I I 1.67.1 I I I I. oz ,
0
0
~
0
CJ)
,...
Table 6 (cont)
PlTIEHT COUNT t1AXll'llt1 TEMPERATURES
RECOttBINANT HEPATITIS B YACCltlE
STUDY I 0813
TREATHENT
DDSt t.S 11CB
PATIENT CLASS! HEALTH CARE PEASOHHEL
I TOTAL VACCINEES I 61 PATIENTSI - DOSE t I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATiotl I NUteER
NAM TEMPfRATUIIE
IOEGf,ORAll
1
Io
--------------------------------------------------------------------------•--------•---I
I 1 I 2 I 3 I 4 I 5 I I WITH
INA>CTEt1P
••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l•••••••••••••••••••••l•••••Q•••••••••••••••••a•••••••••••••~•••••
I I I I I I I I
HOIIMAl I .o I 61 I 60 I 61 I 61 I 61 I I 59
I c 98.47.1 I uoo.o;o I , 9&.47.1 I naa . 0%1 I uoa.07.1 I uoo.0%1 I I , 96.7Y.>
I I I I I I I I
<•'9 I 1 I o I o I o I o I • I I 1
I l 1.6)0 Ic 0.01.1 I 1 0.01.1 I, o.07.1 I l o.or.1 I 1 1.0:1.1 I I, 1.6:I.J
I I I I I I I I
99 - 99. 9 I o I o I 1 I o I o I o I I
I l O.OY.I I I O.OY.l I C 1.67.1 I f D.07.1 I l 0.0:1.1 I I o.OY.I I I I 1.6%1
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
Tu1PERATURE TAKEN I 61 I 61 I 61 I 61 I 61 I 61 I I 61
I ll00.07.1 I 1100.or.1 I ClOO.OY.J I UOD.OY.I I llOO.OZJ I UOO.OY.I I I llOO.Oll
------------------------1----------1----------l----------l----------1----------l----------l---------------------l-----------
nnPERATVRE HOT TAKEN I I I I I O I O I O I O I I 0
I , o.o,o I , 0.01.1 I c 1.oY.1 I c 0.0:1.1 I , o.o;o I 1 0.0:1.1 I I I o.o;o
0
0
.c,
0
-0
Table 6 (cont)
PATifNT CDUff MAXJtllM TEMPERATURES
STUDT I 0&13
TREA111£NT
OOSE· Z.5 MCG
PATIENT ClASSI H[AlTH CARE PERSONNEL
I TOTAL VACCJHfES I 60 PATJENTSI •DOSE] I

1···--------------------···-··----------··------------------·------··-··-·---·--···-----
I DAYS POST VACCIIIAT1014
1I HUl18ER
nAX TEnPERATUI!(
I DEG F, ORAL I
1-·---···-·-···---·-·-·------------··--···---···--··-·--···-·-········-··········-····-·1
I O I l I 2 I 3 I 4 I 5 I I
WITH
I MAX TEMP
••••••••a•••••••••••-••• l•••••••••• ••••••••••• l•••••••••• •••••••••••••••••••••• l•••••••••• ••••••••••• ••••-••••••l•Q••••••••
I I I I I I I I
NORHAl I H I 60 I 60 I 60 I 60 I 60 I I 60
I 1100.01. 1 I 1100.0;0 I noo . o;o I noo.o;o I 1100.0;0 I 1100.0;0 I I noo.or.,
·--··--·-·-······-······1·-········1
TEHPU!ATURE TAKEN I 60 I
·······--·1·····-····1··-····-··1
60 I 60 I 60 I
··-····-··1·-·--···--1
60 I 60 I
·-····-·--·--···-·-·-1I -----·--··-
60
I 1100.0;:1 I 1100.0;0 I noo.or.1 I 1100.or.1 I 1100.0:0 I 1100.0:0 I I noo.or.1
-----·--------------·--·l·---·-·-·-1--·--·---·1----------l------·-··1--·--·····1·-····-···1
nnP£RATURE NOT TAK EN I o I o I o I o I o I o I
···-····-·······--··-1I ········---
o
1 c o.o:o I 1 0.11:0 r I e.or.> I I o.or.> I c o.o:o I I o . or.1 I I I o . or.1
C,
C,
....
l:::
-
Table 7
PATIENT COUtlT NAXI,._, TEHPE~ATUl!ES
RtCOl181NANT HEPATITIS 8 YACCIIIE
STUDY O&ll
l1UA111UIT
DOSE 5 t1tG
PATIENT ClASS HEAllH CARE PERSONHtl
------~---------------------------------------------------------------------------------------------------------------------
I TOTAL YACC1H££S I 121 PATIENTS) - DOSE l I
l---------------------------------------------------------------------------------------1
I t•t.l S r1;s ·1 '{ t,C!:.INUiC·I I NUt18ER
HAX TEtff'ERAT\ff!E
I DEG F, ORAL I
l---------------·--------•--·-·-··--------------·---------------------------------------1
I D I 1 I 2 I :S I '+ I 5 I I
WITH
I HAX TENP
••~••a••••••••••••••••••I••••••••••
I
•••••••••• ••••••••••l••••••••••l•••N••••••
I I
•••••••••••••••a~~••••••~~•••••••••"~••••••
I I
NOl!t1Al I 11'+ 117 116 I lU I 117 116 I I 109
I 1 ~.z:o I CJt..1x1 1 '16.7%1 I 1 9s.e;o I c ,e.:s:o I CJS.CJY.I I I 1 ,o.uo
I I I I I
<99 I 2 1 1 I o I o l I I 2
I I 1.n1 I l.8XI C o.a;o I C o.ox, I I o.o:o C 0.&iO I I t 1.77.)
I I I I I
99 - 99. 9 I 4 2 2 I 5 I z " I I a
I C l.lY.l C 1.71.1 I 1.71.l I I '4.tiO I t 1.71.1 C l.lXI I I C ♦ .6Y.I
I I I I I
100 - 100. 9 I 1 1 l I o I o o I I 2
I c o.87.) I 1 1.ex1 1 a.e:o I t 0.01.1 t , 0.07.1 , ,.ex, t I 1 1.1:1.1
------------------------l----------l----------l----
n11PuATURE TAKEN I 121 I Ul I
·-----l----------l----------l----------l---------------------1-----------
120 I 120 I 119 I 121 I I Ul
I UOO.OY.I I 1100.07.1 I t 99.ZlO I t 99.21.t I I 98.31.1 I 1100.0XI I I 1100.aY.1
------------------------l----------t----------l----------l----------l----------l----------1---------------------1-----------
TEHPtRATURE HOT TAKEN I O I D I l I 1 I 2 I O I I o
I I I.DY.I I I I.OXI I t O.IIXI I C O.IIXI I I l.7Y.) I I O.OXI I I I O.OY.I
0
c:,
--
~
Table 7 (cont)
PATIENT COUNT HAXIi.Jtl TEHP[RATUR[S

RECot1BINANT HEPATITIS B VACCltlE
STUDY O&lJ
TREAfflEHT
DOSE 5 11CG
I TOTAl VACCINEES I 120 PATIENTS! - DOSE 2 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I tufflER
HAX TEHPERATUR!
IDEG F, ORAL)
1---------------------------------------------------···--··------··------------··--··---1
I O I l I Z I J I 'I I S I I I
WITH
NA)( T£HP
••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l••••••••~•••••••••••••••••••••••••••••~•••••••••••••a•l••ae••••••
I I I I I I I I
NORHAL I 11] I 114 I 114 I 116 I us I 116 I I 110
I I 95,0)0 I ( 95.8)0 I ( 9S.8Y.I I ( 97.SY.) I I 96.67.) I ( 97.S,O I I I 92.47.1
I I I I I I I I
< 99 I ,. I J I ,. I 2 I 2 I z I I s
I , J.tor.1 I , 2.s:o I , 1.1tx1 I , 1.1x1 I , 1. 1x1 I , 1.n, I I , ,.,2;,;1
I I I I I I I I
9' - 99. 9 I 2 I 2 I l I l I z I 1 I I 4
I I l.7Y.I I ( l.7:f.l I I o.ex, I ( 0.87.) I I 1,T/.1 I I O.BlO I I ( J.ti7.I
------------------------l----------l----------l----------l----------l------·---l----------1---------------------1-----------
nttPEAATUAE TAKEN I 119 I 119 I 119 I 119 I 119 I 119 I I 119
I I '9.ZlO I ( 99.2l0 I I 99.2)0 I ( 99.2X) I I 99.2Y.I I f 99.2l0 I I I ,,.vo
------------------------l----------l·-----·---l----------l----·-·---l----------1----------1---------------------l-----------
nHPERAtURE HOT TAKEN I l I l I l I l I l I l I I I
1 1 o.et1 I I a.ax, I t o.a;o I t o.aY.1 I I a.BY.I I I a.BY.I I I • o.eY.1
0
0
-""
N
Table 7 (cont)
PATIENT COUNT NAXI'1Ult TENPERATUllES
REC011BINANT HEPATITIS 8 YACCltlE
STI.OY 0813
TRUTl'IENT
DOSE t 5 HCG
PATIENT ClASS' HEALTH CARE PERSONNl:l
J TOTAL VACCIHEES I 115 PATIENTSI - DOSE l I

1---------------------------------------------------------------------------------------I
I DAYS POST VACClHATIOfl I NUt18ER
NAX TEHPERAT~E
CDEG F, OR AU
1-----------------------------------------
I O I l I t I J
------------------------------------------•---I
• 4 • 5 • •
MITH
• l'IAX TEHP
••••••••••••••••••••••••l••••••••••l••••••••••••••••••••• I•••••••••••••••••••••••••••••••• •••••••••••••••••••••••••••••••••
NORl1Al
II 75
II 75
II 75 I• 78
•• 78
•I 78
•• I• 78
I 1100.01.1 I 1100.0Y.l I 1100.01.1 I 1100.01.1 I 1100.01.1. 1100.01.1 I • ClOO . OXI
------------------------l----------
TEl1PERATURE TAKEN I 78
l----------l----------l----------l----------•----------I---------------------I-----------
I 78 I 78 I 78 I 78 I 78 I I 78
. I c 67.81. 1 • I 67,81.1 I I 67,81.1 I C 67.8l0 I I "7 . 81.1 I c 67.81.1 I • I "7.81.1
------------------------l----------l----------
Tu1PERAtURE HOT TAKEN • •3 7 I n
l----------l----------•----------I----------I---------------------
• l7 • 37 I 37 I 37 I
I-----------
• 17
I C l Z.2)0 • I 32 . 21.1 I I JZ.Zl<I I I 32 , Zl<I I I JZ . 21.1 • I 32,21.1 I • I 32.21.l
0
0
...
J;::
v,t
_,
Table 8
PATIENT COUNT MAXIHUl1 TEMPERATURES
RECOt1BIHANT HEPATITIS B VACCINE
STUDY oan
Tl!EATMfHT
DOSE 10 11CG
PATIENT CLASS HEALTH CAI!! PER50NN(L
I TOTAL VACCIH[E5 C 13Z PATIENTSI - DOSE 1 I

1I ---------------------------------------------------------------------------------------
DAYS POST VACCIHA.llON II tM19ER
ffAX TEMPERATURE
CDEG F, OIIAL I
1---------------------------------------------------------------------------------------I
I O I l I t I l I 4 I 5 I I
WITH
I ttAX TfHP
~•••••••••••••••••••••••l•••••••••• I•••••••••• •••••••••• •••••••••• •••••••••• •••••••••••••••••••~•••••••••••••••n•••••••
I I I
NORMAL I . 114 I ua 119 119 118 ue I I 111
89,17.1 I I 9l.S7.I I 9J , 07.I I 9J.07.I I 92.27.1 I 92,27.1 I I I a,.or.1
I I I
<99 I 4 I 7 s 2 ti s I I ,.
J.17.J I I 5.47.1 C J.97.1 C l.6l0 C l.17.1 I J.'IXI I I I l.lXI
I I I
99 - 99. 9 I 10 I 4 4 6 6 s I I n
7.8l0 I I J.17.1 I J.liO C 4.T/.1 I 'o.77. 1 I J.'IXI I I C 10.lXI
I I
100 - 100. 9 I o I o o l O o I
I I O,G1.I I c O.OiO I O.OiO I , .87.1 I 0 . 07.1 I 0.07.1 I I C 0 . 8:/.1
------------------------ l----------l----------1----------l----------l----------l----------l---------------------
,u1P1RATURE TAKEN I 128 I u, I 128 I U8 I 1211 I 1211 I Il-----------
129
I c 97.07.1 I 1 97.TI.I I C 97,0iO I I 97.0lO I I 97.07.1 I C 97.07.I I . I I 97.71.1
------------------------ It----------l----------1----------1----------1----------t----------l---------------------1--··--------
nmotRATlllll! NOT fAl([M 4 f ] I 4 I 4 I 4 I 4 I I l
I C J,07.1 I C t.~I I C J.OY.I I I J.07.1 I I J.07.1 I C J.07.I I I I 2.3i0
-
0
t
-P
-
Table 8 (cont)
PATIENT COUNT 11AXIt1Ult TENPERATUIIES
RfCot181HANT HEPATITIS 8 VACCINE
STIJOY t 01113
TRf:AfflatT
DOU 10 t1CG
PATIENT CLASSt HEALTH CARE P!RSOtlNfL
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES I 1Z5 PATIENTS>· 005£ 2 I
l--------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I tM18£R
ttAX TEHPERATUII[
IDEG F • 011ALI
1
I
---------------------------------------------------------------------------------
I I 1 I Z I J ( '- I 5 I I
·-----1 MITH
I 11Al( TEMP
"••••••••••••••••••••.. •••••••••••••••••••••••••••••••••••••••••••• I•••••••••• •••••••••• ••••••••••l•••••••••• •••w••~•••
I
HOl!l1AL I 109 I 112 I 112 I lU I 114 111 104
9Z.4)0 I C 94 . 97.1 I C 94 . 97. J I I '5 . 87.1I C 96.67.> C 94.17.1 I o e . 1r. ,
I I I I
<99 I 4 I J I 4 I z I 2 l :s
J.47.1 I C Z.57.1 I t J.4l!I I I l . 7ZI I C 1. 7ll c 1.97.1 I z . sr.t
I I I I
9'1 - "'·" I !5 I l I z I l I z s 10
lt.21.I I I Z.57.1 I l I. Tl.I I I 2.s;o I ( 1.71.) l lt.t)O I 8 . 5Z)
I I I I
100 - 100. 9 I o I o I o I o I o 1 1
I , e.or.1 I , o.ox, I c o.07. l I , 0.07.t I , 0.01.1 c o.az1 I I o.a:o
------------------------l----------l----------l----------l----------l----------l----------l---------------------1-----------
TEl1PIERATUl!E TAl< !H I 118 I 118 I 118 I ua I 118 1 ua I I ua
I I M.ttio I c 9"·"'" I c 94.4Xt I c .,._ _,.,o I c 94.47.l I c 94 . 47.1 I I 1 9tt.4i0
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEffl'El!ATUl!t NOT TAKEN I 7 I 7 I 7 I 7 I 7 I 7 I I 7
I C 5 .6l'-I I C 5.6)0 I l 5.610 I C 5.6i0 I c 5 ,6Y.I I t 5.67.I I I I S.6XI
0
0
...
.,:,
<JI
-
Table 8 (cont)
PATlEMT CO\ffl 11lX1'1Jt1 TEHPERAT\JllES
REC01181NANT HEPATITIS 8 VACCINE
STUDT 081]
lREATffl:NT
DOSE 10 NCG

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOtf I NUt18ER
11AX Ttt1PtRA1Ulll
I DEG F, Ol!Al I
l------------------------•--•-----------------------------------------------------------1
I O I I I t I J I 4 I s I I I
WITH
MAX TEl1P
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••••••••••••••••••••••••l•••••••••••••••••••••I•••••••••• ............
NOlll1Al 71 I 71 I n I 72 I 7t I 7t 71
92.27.1 I I 93.4)0 I I 93.5?.I I I ~.77.1 I I n.s:o I I 93.57.1 92.2Y.)
I I I I I
< ,, l I 2 I l I t I J I J l
J.9:o I 1 2.6:'.I I I 11.9:t.l I I 2.67.1 I I 11. 9:t.> I I 3.97.) l.li!)
I I I I I
99 • 99.9 2 I l I 2 2I I z I t 4
Z.61.l I I J.9l0 I C 2.6i!l I C t.67.l I I 2.6)0 I I 2 .t.Y.) 5.2;()
100 - 100. 9 I l I O I o I O I O I II I I l
I I 1.1:n I I o.or.1 I C o.o.o I C o.o:o I C 0.0iO I C o.o:o I I I l.]7.1
------------------------1----------1----------1----------1----------1----------1----------1---------------------t-----------
TtHPtU.TUAlt TA!tlN I 77 I 76 I 77 I 76 I 77 I 77 I I 77
I I 70.6iO I I 69. 77.1 I I 70.67.) I I 6'. 77.) I I 70.6i!) I C 70.t.lO I I I 70.6Y. I
------------------------1----------1----------l----------l----------l----------l--------·-1---------------------l-----------
nMPEAATimE NOT TAKEN I 3Z I Jl I 32 I ll I l2 I l2 I I 12
I t u.-.u I 1 110.l½> I I n.":o I 1 111.1;0 I I z, ...z, I 1 2,.4;:1 I I r 29.4?.I
0
0
-
~
0-
-
Table 9
PATIENT COUNT t1AXI11Utt TEHPERATURES
RECOHl!INANT HEPATITIS B VACCIH£
!ITUOY 0913
TIIU Tl1EHT
DOSE 2D HCG
PATI[Nf ClASS HEAlTH CM! PERSONMEl
I TOTAl VlCCIN\ES C 7 PATIENTS) - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I NU118ER
HAX TEHPERAT\JIIE
I DEG F, OIIAL I
1---------------•--·•-••--••••••••·•-----------------------------•-····--•--------------I
I O I 1 I t I J I 4 I 5 I I I
WITH
t1llC TEHP
•••a••••••••••••••••••••l••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l•••••••••al••••••e•~•l•a••G•••••
I I I I I I I I
NOAHAL I J I J I J I J I 3 I 3 I I 3
I I so.o:o I c so .o:o I c so.ox, I c so.o:o I c so.o;o I c so.a;o I I I so.o;o
I I I I I I I I
<H I 2 I 3 I 3 I 3 I 2 I J I I l
I I JJ.Ji'.I I C 5D.07.1 I C so.o;o I I so.o:o I C 33.37.1 I I 50.07.1 I I I 16.77.1
I I I I I I I I
99 - 99.9 I 1 I o I o I o I l I o I I 2
I C 16.7XI I ( 0.D7.1 I C 0.01.1 I C 0.D7.1 I C 16.7)0 I I 0.07.1 I I I J3.3XI
------------------------l----------l----------l----------1----------l----------1----------1---------------------l-----------
nnPtRATUl!E TAKEN I 6 I 6 I 6 I 6 I 6 I 6 I I "
I I es.77.1 I I 85.77.1 I I as.n, I C 85.7%1 I ( 85.71.1 I I es.n, I I C 85.71.1
------------------------l----------l----------l----------l----------l----------l----------l---------------------l-----------
nt1PERATURE HOT TAKEN I l I 1 I l I l I 1 I l I I 1
I C 14,37.) IC 14.37.1 I I 14.37.1 I I 14.37.1 IC 14.37.1 I I 14.37.) I I I 14.37.1
0
0
-
.e
.....
Table 9 (cont)
PATIENT COUNT HAXIl!ll1 TEHPEAAT'-"ES
AECOHll!NANT HEPATITIS 8 VACCINE
STUDT 0813
TREATt1EHT
OOSE 20 t1CG
PATIENT CLASS HEAllff CARE PERSONNEL
-~--------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES ( 't PATIENTS) - DOSE Z I
l--------------------------- ------------------------------------------------------------1
I DAYS POST VACCINATION I NU!18ER
HAX TEHP£AATlmE
I DEG F, Ol!AU
1-------------------------------------•-----•------------------------·-··-··--·--·------I
I O I 1 I 2 I 3 I 't I 5 I I
NITH
I t1AX TEMP
eaae•Dn•••••••••••••••e•l•••••••••al••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••~••••••••e•••
I I I I I I I I
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- -- 00420
tu::COMBINANT YEAST H'EPATITIS B VACCINE: SIDE EFFECTS AWD

IHMUNOGENICITY COMPARED WITH PLASMA-DERIVED HEPATITIS 8 VACCl~E.
Morton Davidson and Saul Krugman
NYU Medical Center, New York, N.Y.
A yeast recombinant hepatitis B vaccine (Merck Lot no. 972/C-
K444) was evaluated in 197 seronegative health professionals, 21-
30 years of age. The clinical and antibody responses were
compared with the results of a previous &imilar study using a
plasma-derived hepatitis B vaccine (Herek Lot no. 751).
~he vaccine was administered ate, land 6 months to the
following three groups: l) 51 adults who received a li mcg dose
of recombinant vaccine;-2) 56 adults who received a S mcg dose -of
recombinant vaccine, and 3) 47 adults who received a 20 mcg dose
of plasma-derived vaccine. The three groups included medical
students, house staff, and nurses who were of comparable age and
sex.
Results
Side effects were ne9ligible in all three groups. They
consisted of transient, local soreness at the site of the
inoculation in about 25\ of the vaccinees in each group. No
systemic reactions wer~ observed.
The seroconversion rates and geometric mean titers are
summarized in the Table. The results re essentially the same for
all three groups. Under -the conditions of this study the S mcg
and 10 mcg doses of recomblnant hepatitis B vaccine were, just as
im.~unogenic as a 28 mcg dose of plasma-derived hepatitis B
vaccine.
Comment
A recent report by Jilg et al (Lancet 1984; 2:1174-75)
described a similar study in 36 seronegative medical students and
laboratory-workers whose age and sex were comparable to those in
our groups. They stated that "the immune response in the
recombinant vaccine group was less pronounced during the first
months than in the plasm~ vaccine group, as shown by lower
seroconversion rates and lower ~ean anti-HBs levels." Our results
in 107 similar.recipients of the recombinant hepatitis B vaccine
do not support this conclusion. ..
It is obvious that valid conclusions cannot be drawn from
studies involving either 30 or lie vaccinees, M&-re extensive
studies ~ill be required to determine anti-HBs response and its
persistence in recipients of recombinant hepatitis B vaccines.
D1vidion Krue n s. ft c 1n•nt y st h pmtit1$ D v ccin~: Sidi ffects

~nd 10Yno9 n1c1ty t~ijrod ~1th · pl s -der1v d hep11tit1s B vacc1ne.
Subfii1tt~d for pub11c t1on to Hepmt1t1i Sc1ent1~1c @r1nd1.
00421
TABLE
Seroconversion Rates and Geometric Mean Titers of Seronegative

Adults Who Received Recombinant Yeast Hepatitis B vaccine (Herek
Lot No. 972/C-K444) or Plasma-Derived Hepatitis B Vaccine (Herek
Lot No. 751).
T imE Recombinant Hepatitis B Vaccine

Interval 19 ll\CCI dose 5 mc0 dose
anti-Has mlU/ml S/N Ratio ant:i-HBs mlU/ml ~/N Ratio
(Months) reseonse GMT GMT res2onse GMT GMT
0
1
-
22/51 (43%)
-42 -19 -
21/56 (37%)
-ss -
25
2 48/51 (94%) 88 37 51/56 (9.,l%) 69 38
l S0/51 (98%) 145 52 52/56 (93%) 128 51
6 49/50 (98%) 321 63 53/56 (95%) 184 42
8 45/46 (0~%"1 1CH1 t ,;1.i 49/50 (98%"1 839 1 ?I,
Vaccine given ate, 1 and 6 months.

Age Range: 21 - 30 years
Time Plasma-Oer1ved Hepat1tis B Vaccine

Interval 29 mccr dose
anti-HBs S/N Ratio
{Honths! res0onse GMT
0
1
-
18/47 (38%)
-20
2 34/47 (79%) 37
3 45/47· (96%) 79
6 44/47 (94%) 94
7 46/47 (98%) 141
Vaccine given at s, land 6 months.
~ge rsng~: 21 - 30 y rs
L
,·:~~....~. .l i;'~,""t,,·;~;t:-:-.,.....:,
'.B:;tll!!~~-r.;:
·:,·;'
REPORT NO. 3
in Support for a License Application for
RECOMBIVAX
(Yeast Reco:mbinant Hepatitis B Vaccine, MSD)
CLINICAL DATA* ~
VOLUME 2 OF 3
Research Labora ories
I ■ 11 111 11111
;,;,~;j~;,
• -: _·,:7;;~~-;i,,'•~; . . . .~
F
HEALTH CARE PERSONNEL
/HEALTHY ADULTS (CONTD)
00'&22
PROGRA'4: Alum-Adsorbed Yeast Recombinant Hepatitis 8 Vaccine,

Study 815
PURPOSE: To compare antibody and clinical responses to yeast

recombinant and plasma-derived hepatitis B vaccine
among:
Mentally retarded individuals who are negative for
2. Health care personnel who are negative for
VACCINE: 1. Yeast Recombinant Hepatitis B Vaccine

Lot 993/C-K937 (20 mcg/HBsAg/ml)
2. Plasma-Derived Hepatitis B Vaccine
Lot 2277K (20 mcg HBsAg/ml
PRIMARY Solko W. Schalm, M.D.

INVESTIGATOR: Department of Internal Medicine and Gastroenterology
University Hospital D1jkzigt
Rotterdam, The Netherlands
SECONDARY Dr. Rudolf A. Heijtink

INVESTIGATORS: Department of Virology
Erasmus University ·
Dr. Maria Alida van de Velde
Dr. ~r. Willem van den Bergh - Stichting
Noordwijk, The Netherlands
STUDY LOCATION: Dr. Mr. Willem van den Bergh-Stichting

University Hospital D1jkzigt
OATE STUDY INITIATED: December, 1985
DATE STUDY CO~PLETED: In progress
32341/1
1/21/86
00423
Study 815

mentally retarded individuals. and ~O health care
personnel, who are negative for HBsAg, anti-HBc,
anti-HBs. have a normal ALT and have not previously
received any hepatitis B vaccjne.
STUDY PROCEDURE: ~entally retarded individuals and health care
personnel are randomly assigned to receive either
yeast recombinant or plasma-derived hepatitis B
vaccine, stratified by sex and age.
Mentally retarded individuals and health care
personnel receive a 0.5 ml (10 mcg HBsAg) or a 1.0 ml
(20 mcg · HBsAg) intramuscular injection of yeast
recombinant vaccine or a 1.0 ml (20 mcg HBsAg)
intramuscular injection of plasma-der1 ved vaccine at
o, 1, and 6 months.
The temperature of each vaccine recipient and any
local or systemic complaints are recorded for five
days after each injection of vaccine.
A blood sample is obtained from each study participant
approximately three weeks before the first injection
of vaccine. Post-vaccination blood samples are
obtained from mentally retarded individuals at 3, 7,
and 12 months and from health care personnel at 1, 2,
3, 6, 7, 9 and 12 months. Blood samples are obtained
at 24 months from those participants who have
seroconverted.
All serum samples are assayed for HBsAg, anti-HBc,
anti-HBs and ALT. Samples may be assayed for yeast
antibody. In addition, samples with an anti-HBs titer
~ 25 mlU/ml may be tested for anti-! and anti-t
subtype specificity.
RESULTS: Clinical follow-up data and serologic results are not

yet available. The study continues in progress.
32341/2
1 /21 /86
-
ID
co
►
C
;:)
~
V')
00424
PROGRA~: Alum-Adsorbed Yeast Recombinant Hepatitis B- Vaccine,

Study 816

recombinant hepatitis B vaccine among:
1. adult dialysis patients negative for hepatitis B
serologic markers.
2. health care personnel negative for hepatitis B
serologic markers.
serologic markers, who previously received plasma-
derived hepatitis B vaccine and were nonresponders
(anti-HBs negative).

PRIMARY Stanley Plotkin, M.0./Stuart Starr, ~.D.

INVESTIGATOR: Division of Preventive Medicine
34 Street and Civic Center Boulevard
Philadelphia, Pennsylvania 19104
STUDY LOCATION: Biomedical Applications of Lehigh Valley

2015 Hamilton Avenue
Allentown, Pennsylvania 18104
Dialysis, Inc.
1230 Burmont Road
Drexel Hill, Pennsylvania
The Kidney Center of Delaware Count
15th Street and Upland Avenue
Chester, Pennsylvania 19013
The Kidney Center of Chester County
960 East Lincoln Highway
Oownington, Pennsylvania 19335
25381/1
l/21/86
00"25
Study 816
DATE STUDY INITIATED: ~ay 14, 1984
DATE STUDY CO~PLETEO: In progress
STUDY POPULATION: The study population consists of 40-50 adult

dialysis patients (including previous nonresponders
to plasma-derived vaccine), and 20-25 health care
personnel, of either sex (excluding pregnant women),
who are negative for HBsAg, anti-HBc and antt-HBs,
and have a nonnal ALT level. Dialysis patients
(excluding non responders to plasma-derived vaccine)
and health care personnel have not previously
received any hepatitis 8 vacctne.
STUDY PROCEDURE: Dialysis patients are assigned to one of two groups,

stratified by sex and age, to assure that patients
in the two groups are similar. Health care
personnel constitute a third group.
Dialysis patients receive 1.0 ml' (20 mcg HBsAg) or 2

x 1.0 ml (40 mcg HBsAg) intramuscular injections of
vaccine at 0, l, and 6 months. Health care
personnel receive 0. 5 ml (10 mcg HBsAg)
intramuscular 1nject1ons of vaccine according to the
same regimen. Vaccine recipients record their
A blood sample is obtained from each study

injection of vaccine. Post-vaccination blood
samples are obtained at 1, 3, 6, 8, 12 and 24
months.
All serum samples are assayed for HBsAg, ant1-HBs,

ant1-HBc, and ALT. Samples may be tested for yeast
antibody. In addition, samples with an anti-HBs
t;ter > 25 mIU/ml may be tested to determine anti-a
and anti-& subtype specificity. -
10 mcg Lot 974/C-~446 at 0, 1, and 6 months
25381/2
l /21 /86
00£12b
Study 8H,
RESULTS: (Contd) l. Number Vaccinated:
Injection No.
_1_ _L ...L
8 B 6
Serologic data at 7/8 months are available for 5
health care personnel. At 7/8 months, 80% (4/5)
of health care personnel seroconverted (S/M
~2.1) and developed protective levels of
ant1-HBs (mIU/ml ?,10). The G"1T for all
vaccinees was 37.9 mIU/ml at that time. Among
responders with a .t iter of S/N ~2 .1 and
mlU/ml ~10 the GMT was 127.2 mIU/ml.
By 12 months, 60% (3/5) of health care personnel
retained an anti-HBs titer of 111[U/ml >10. The
GMT for all vacc1nees was H,.4 mIU/ml- lit that
time.
Ant 1-HBs responses at l through 12 months are

health care personnel following the first two
injections and for 6 health care personnel
following the third injection of vaccine.
Clinical complaints and maximum temperatures
reported following each injection are provided
in Tables 2 and J. In sumnary:
Clinical %Frequency by Iniection No.

Complaint __l_ 2 3
Injection Site 25 (2/8} 25 (2/8) 17 (1/6)

Systemic 38 (3/8) 25 (2/8) 17 (1/6)
25381/3
1/21/86
00427
Study 816
RESULTS: (Contd) Ho serious or alarming adverse reactions

25381/4
l /21/86
Table 1
ANTIBOOY RESPONSES FOllOWIHG VACCINATION WITH RECOt18INANT HEPATITIS B VACCI NE
STUDY 11816
POPULATION I HEALTH CARE PERSONNEL
DOSE 10 t1CG
LOT CKft46
REGI'1EN 0, 1, ANO 6 HOHTHS
INITIAL SEROLOGY: NEG ATIVE
I 7. WITH ANTI-HBS I Gffl' (11IU/11U I

l---------------------------------------1-----------------------------------------------------I
I I I RESPOHDERS I
T IME
(tlOHTHS )
l---------------------------------------l-----------------1
I SIN >s t.1 I 11IU/t'IL >= 1 0 I Al l VACClHEES I -----------------------------------I
9/H >= t.1 I 111U/11l >= 10 I
..................................................................................................................
I I I I I I
1 HONTM I 25Y. ( t/81 I 13,: (1/8) I 1.2 I 13.Z I 86.5 I
I I I I I I
:s ii,oNTHS I "or. (t/51 I 1tor. lt/51 I 7.1 I 355.S I 3 55. S I
I I I I I I
6 110HTltS I 7SY. 13/41 I !IOZ U/4) I 6.6 I 18.. f 30 . 6 I
I I I I I I
7/8 110NllfS I BOY. (41!1) I &OY. ("15) I 37.9 I 127.Z I 12 7.t I
I I I I I I
12 HOHTHs I eor. (4/!11 I 6or. n1s I I 16 .4 I -.-.. 7 I .e a. 9 I
I I I I I I
...................................................................................................................
0
0
"'
N
0,
Table 2
PATJENT COUNT CLINICAL CottPLAINTS
RECOH&JNANT HEPATITIS 8 VACCINE
STUDY t 0816
TREATHEHT
LOT HUHDEII CK446
DOSE : 10 t1CG
PATIENT CLAS9l HEALTH CARE PERSONNEL
I TOTAL VACCIHEES ( 8 PATUNTS t - DOSE 1 I

l----------------------------------------------------------------------------1
I DAY9 POST VACCINATIOH I NUt1BER
CllHICAL
COHPLAIHT9
l----------------------------------------------------------------------------1
I O I l I 2 I 3 • 4 I 5 •
WITH
ICOt1PUIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••o••l•••••••••••••••••••••l••••••••••••••••••a••I•••••••••••••••••••••
I I I I I I • I
RUCTIOH, LOCAL IINJECT. SlTU I 2 I O I O I O I O I O I I 2
. I f t!J.OlO I I O.DlO I ( 0.0)0 I ( 0.0)0 I ( O.OY.I I ( 0.01.1 • I I U.OY.J
-----------------------------------1----------l----------l----------l----------l----------l----------l----------1-----------
PAtH I 1 I O I O • 0 I O I 0 I I l
I , 12.57.1 I t 0.0;:1 I t 0.01.1 I t D.oi:, I 1 0.01.1 I I o.o:o I I 1 12.s:o
I I I I I I I I
SORENESS I 1 I O I O I O I O I II • I 1
I I 12.57.J I I D.07.I I I D.DlO I I D,CIY.J I I O.OY.I I ( O.OlO I I I lZ.57.1
-----------------------------------1----------l----------l----------l----------l----------1----------l----------l-----------
snTENIC I 1 I 1 I 1 I 3 I z I z I I 3
I I U.57.J I I lZ.5)0 I ( 12.51.) I I 37.s:o I I Z!S.0)0 I I Z!UJY.I I I C iJ7.5Y.t
WHOLE 800T/1iEHERAl I 0 0 0 z I l 1 l
0.07.J o.o;o ( o.o:o I 25.D7.J I ( lZ.57.1 I U.57.1 25,0)()
' z
I
HEADACHE I 0
0.0:X)
'
0
0.07.1
'
0
0. 07.) I ZS.07.I ' 1
I lZ.5Y.l
1
I lZ.SlO
2
I 25.0)0
RESPIRATORY I 1 l l 1 1 0 1
12.57.) I lZ.57.J ' 1Z.5Y.) , 12.s::o I lZ.57.1 ( o.o:o r 12.s;o
UPPER RESPIRATORT ltlfECT., HOS I 1 1 1 1 1 0 l
( 1Z.5Y.) ( lZ.SY.J I lZ.57.1 I 1Z.5Y.I o.o:o ( 12.5¼1
t1U5CULOSKt:LETAL I
12.57.t
0 0 0 0 0
' 1 1
o. 07.J ( •• 07.J I 0. Cl?.J I 0.01.1 ( 0.0)0 ( 12.57.1 U.57.)
14RIST PAIN I 0 0 0 0 0 1 l
0.0)0 ( 0.01., f O.OY.I I 0.07.1 ( 0.0)(1 I U.!>iO 12.57.)
HIP PAIN l 0 0 0 0 D 1 1
D.OY.J ( ,.ox, I 0. Ill! I I O.OY. I ( ll.OY.I I U.SY.I lZ.57.)
DIGESTIVE SYSTEN I 0 0 0 1 1 0 1
•• 01.) f 0.01.1 I o. 07.1 f 12.57.1 ( lt.5)() ( 0.0)(1 u.s:o
0
0
~
IV
,0
Table 2 (cont.)
PATIENT C0UNT CLIHICAL COttPLAINTS
RECOltBIHANT ffEPATIT~S B VACCINE
STUUY 0816
TRt ATNENT
LOT NUtfflER I Cl<446
bOSE 10 NCG
PATUNT CLASS: HEALTH CARE PERSONNtl
-------------------~----------------------------------------------------------------------------------------------
I TOTAL VAtCtH£U I 8 P ATt£HTS J - DOSE 1 I
---------
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION • .«Jt18ER
CLIMtt l l
t011P U INT9
l---------•------------------------------------------------------------------1
I O I 1 • 2 I 3 I lt I 5 I ltOHPLAIHTS
MITH
•""•••••••••• ..•••••••••••••-•••••l•••••••-•l•••••••••••••••••••••l
I I I I••••••••••l••••••••""I••••••••••••••••••••••••••••••••
I I I I
HAUSl:A I O I O I O I 1 I 1 I O I I 1
I ( 0.07.1 l ( o.ou I ( o.oY.1 l , 12.s:o I , 12.sY. 1 I 1 0. 0:1.1 I I 1 12.s;o
-----------------------------------1----------I----------I----------I----------I---------I----------I----------
PERSOtlS WITH COHPU tNTS I 3 I l I 1 I l I Z I 2 • II-----------
4
I ( 11.57.> • 1 12.57. > I 1 12.sr.1 I , 11.sr., I , zs.o;o I I zs.o:o I I , so.oz,
-----------------------------------l----------1----------1
PERSOHS MITH MO COtfflUINTS I 5 I 7 I----------l----------1---·------1----------I----------I-----------
7 I 5 I 6 I 6 I I 4
I I 61'!.57.) I I 8 7.57. ) I I 87.57.1 I I 62.s;o I I 75.0lO I ( 75.o:o I I I SD.OZ)
-----------------------------------1----------I----------I-----
PERSONS MITH NO DATA I O I O I .-O---l----------1----------1----------1
I O I O I O l---------- lI-----------
0
I , • .or., I , o. 01. 1 I , o. ox , I , o. ox, I , o. o;o I , o. o;o I I , o. oz ,
0
0
~
~
0
Table 2 (cont.)
PATIENT COUNT CLINICAL CONPlAINTS
RECOlfllINAHT HEPATIT~!I 8 VACCINE
!ITU>Y 0816
TIIEATt1EMT
lOT H\Jt19£R Ck44b
DOSE I 10 t1CG
PATIENT CLAss: HEALTH CARE PERSONNEL
I TOTAL VACCINEES ( II PATIENTS) - DOSE t I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NlfflER
CLINICAL
CONPLAIHTS
1----------------------------------------------------------------------------I
I O I 1 I Z I 3 I ,. I 5 I
WITH
ICOMPLAINTS
•••••••••••••••••••••••••••••••11111••1••••••••••1••••••••••••••••••••••••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
I • I I I I I I
REACTION, LOCAL UHJECT. SITE I I 2 • 1 • 0 • 0 • 0 I O I I 2
I ( zs.oio I ( 12.s:o I f o.o:o • 1 o.o:o I f o.or., I f o.o:o 1 1 1 zs.o:o
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
!IORtNtss I 2 I 1 I o I o I o I o I I 2 ·
I ( ts.ox, I I 12.sr.1 I ( 11.0:0 I I 0.0)(1 I I o.or., I C o.or.t I I I 25.07.)
-----------------------------------l----------l----------l----------•----------l----------l----------l----------l-----------
svsnt1Ic I 1 I o I 2 I 1 I o I o I I 2
I I 12,57.) I ( 0.07.) I ( 25.07.) I I 12.s:o I I o.o;o I I 0.07.) I I I zs.o:o
----------------------------------------------------------------------------------------------------------------------------
I I
MflOLE 80DY/GENERAL I 0 0 2 0 0 I
( 0.07.) ( 0.07.) t 25.07.) I 0. 07.) I O,OY.) I
0
o.o:o '
I ZS.DY.I
rATIGUE/W!AKHE!IS I 0 0 1 0 0 Cl 1
0.07.) ( 0.07.) I 12 .5)0 I o.o:o I o.o;o I 0.07.1 I 12 .SiO
HEADADfl! I 0 0 l 0 0 0 1
0.07.1 ( o.o:o C 12,57.) o.o;o ( 0.07.1 I o.o;o ( 12.SY.)
'
NUSCULO!IKELl!:TAL I 0
O.0Y.) I
0
0.0)0
1
( lt.57.1 ( •
0,07.1 I
0
0.07.) I
0
0,0Y.I
1
I 12 .5Y.t
NtCK PAIN I 0 0 1 0 0 0 1
o.o:o ( o. 07.1 1 12.s;o I 0.0)0 0.0)0 a.ox, I 12.57.)
CtGE!ITlVE !IYSTEn I 0 0 1 1 I
I
0
' 0 1
0.0:1.1 I O,OY.I 1 12.s;o I 12.57.1 I I 0.0)0 O.Ol() ( 12.SiO
HAU!IU I 0 0 l 1
I
I 0
' 0 l
o. 07.) I o.or., I 12.5?.I I 12.57.1 I I o.oz, I O.OY.I C 12.5:.!I
I
'HERV1lUS SYSTEn I 1
12.57.)
0
C,,07.1 I •
c,.o:o I
0 I
o.o:o I I
0
o.o;o
0
O.OY.I
~ 1
I c 12.Sr.J
V!RTIGO/IIIZZINESS I 1
' 0 0 0
I
I 0
' 0
I
I 1
12.sz, I 0. 07.J I 0,0?.I I 0.0?.I I C O.OY.I I O. OY.I I c U.5%1 0
0
-
~
~
Table 2 (oont. l
PATIENT CIJlffl CLINICAL Cotff'LAINTS
RECOt18INAHT HEPATITIS 8 VACCINE
STUDY 0816
TREATHEHT
LOT NUtfflER Ck4"6
DOSI: JD HCG
PATIENT CU!l!I HE ALTH CARE PERSONNf:l
I TOTAL YACClNEE! C 8 PATil!'NJS J - DOSE t I

l----------------------------------------------------------------------------1
CLINICAL
COHPLAINT9
1------------------------------------------------------------------------•---I
I O I l I 2 I :, I • I 5 I MITH
ICOMPLAINT!!
•••••••••••••••••••••••-••--••••••l••••••••••l••••••••-1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
-----------------------------------1----------l----------1----------
PERsONs W ITH COMPLAINTS I ! I 1 I 2 I
I----------I----------I----------I----------I-----------
l I o I o I I 2
I r 2s.o;:1 I c u.s,o I c ts.o:o I , u.s;:1 I , o.o;:, I 1 0.11;:1 I I I n.o;o
-----------------------------------1----------I----------I----------I----------I----------
PERSONs HITH HO COffl'U INTS I 6 I 7 I 6 I 7 I 8
I----------I----------I-----------
I 8 I I 6
I I 75.0?.J I c 87.Si:J I C 75 . 0lO I c 87.5%1 I 1100.0;0 I llOO.D?.t I I C 75.0?.I
-----------------------------------1----------I----------I----------
PtAsoos 1,11m HO ou.1 I o I o I o I
I----------I----------I----------I----------I-----------
o I o I D I I o
I I 0.0;:1 I I 0.07.J I C O.OY.I I I O.Oi:J I I 1'-D?.t I I D.D?.I I I ( O.OlO
0
0
l::
IN
N
Table 2 (cont.)
PATI ENT COUNT CLINICAL COMPLAINTS
REC0t18IHANT HEPATITIS B VACCINE
STUDY 0816
TREATtt[NT
LOT NlfflB[R CK446
DOSE 10 ttcG
PATIEHT CLASS: HE ALTH CARE PERS~ fl
I TOTAL Vl CCINEES I 6 PATIENTS) - DOSE J I

1----------------------------------------------------------------------------
• OAlS POST VACCINATIOH
II NUmlER
l----------------------•-----------------------------------------------------1
CLINICAL
Cot1P LA INTS • 0
..............................................
•
•
•
, I
.........• I 2
,
.......... I 1
..........,I 4
.......... ,
I S I
, WITH
•COHPLAJNTS
..•.......•..........•..........
REACTION . LOCAL ! I NJECT. SITE> • 1 • 0 II O
I
I O
I
I o I
I
O
I
I •
I 1
• I 16 , 7i0 I C O.OY.> I I O.OY.> I C 0.0:1.1 I I o.o,o I I o.o:o I I I 16 .1;0
-----------------------------------1
SORENEss I ----------l----------l----------1----------•----------t----------•----------
1 I o I o I o I o I o I It-----------
1
I I 16. 77. > I C O. 0% I I I O. OY. > I C O. DY. I I C D. o:r. t I C o. o:o I I c 1 6 . 7Y. l
----------------------------------l----------l----------l---------l----------1
srsn ttIC l 1 I 1 I 1 l 1 I
----------1----------1
1 I 1 I
---------- Il-----------
1
I C 16.7Y.l I ( 16.7%) I I 16.7?.) IC l6.7i0 I I 16.T/. ) I I 16.7:cl I I I 16.7Y.l
---------------------------------------------------------------------------------------------------------------------------
1 I I I 1 I I I
OI6ESTIVE SYST[l1 I l I 1 I 1 I 1 I 1 I 1 I I 1
I ( 16.77.) IC 16.T/. ) I I 16.7)0 If 16.T/.I I I 16.77. J I I 16.77. J I I I 16.7Xl
I I I I I I I I
NAUSEA I J I 1 I 1 I 1 I 1 I 1 I I l
I C 16 , 77.J I I 16.T/.J IC 16.7?.l . f 16.7Y.I I I 16 . T/.l IC 16.77.I I I c 16.7i0
----------------------------------- Il----------l----------l----------l----------1
n Rs011s WITH COMPLA INTS 2 I 1 • 1 I 1 I
----------l----------l----------
1 I l I
t-----------
I t
I I 11 .31. J I ( 16.T/.l I I 16.71.l • I 16.T/.l I I U.7:1.) I C U.77.) I I I 33.37. 1
-----------------------------------l----------l----------
PERSONS Wlnt HO Cotfl'U lNTS I 4 I 5 l----------1----------1----------1----------I----------
I 5 • 5 I 5 I 5 I II-----------
4
I 1 66.7Y.I I I n,:,;o I c 8'3 . '37.l I t 1'13.37.1 t c aJ.J;o I c aJ.37.1 I I t 66.77.1
-----------------------------------l----------l----------l----------l----------l----------1----------I
PUs01~s Wint NO DATA I o I o I o I o I o I o I
----------I-----------
I o
f I 0.D7. J I C 0. 0)0 I I 0.D7. ) I I 0 .0%) I ( 0.07.1 I ( 0 .07. ) I I I D.07.)
0
0
~
""
~
Table 3
PATIENT COU4T NAXIt1Ul1 TENPERATURES
RECOl1BINANT HEPATITI~ B VACCINE
STUDY 0816
TRUTIIENT
LOT NUMBER CK446
DOSE I 10 11C6
PATIENT CLASS: HEALTH CARE PERSDM«L
I TOTAL YACCINEES ( 8 PATIENTS! - DOSE 1 I

Il---------------------------------------------------------------------------------------1
DAYS POST YACCIMATION I NIJttBER
1---------------------------------------------------------------------------------------I
NAX TEMPERATURE
tDEGF,ORAU
........................ ,I
IO
,I
.......... I..........
1 I 2
,I
.......... I..........
J I 4
,I I 5
,I
..........•.......... I
,I ,
NlTH
...•...... I........... l.........
I
t1AXTENP
,I
.
<99 • 7 I a I a I a I 1 I a I I 7
I l 87.s:o I U00.0)0 I noo.o;o I UOO.OY.J I ( 87.SiO I (lOO.liO I I I 87.SY. I
I I I I I I I I
99 - '19. 9 I l I t I o I o • l I e • I l
I , 12.sY.1 I , o.o:o I , o.o;o I , 0.0;,.1 I ( u.sz, I 1 0.1;,.1 I I , 12.sr.1
------------------------1----------1----------I---------- I----------I----------I----------I--------------------I-----------
TEMPERAlUIIE TAKEN I 8 I 8 I 8 I 8 I 8 I 8 I I 8
I uoo.oio I uoo.o;o I uoo.ox , I UOO.OiO I noo.or. , I 1100.or.1 I I n oo.or.1
------------------------ l---------- l----------l----------l----------l----------l----------l---------------------l-----------
n:11PER&TU1u: NOT TAKEN I o I o I o I o I o t • I I · o
1. ( 0 .0)0 I I O.OY.) I ( O.OY.J I ( o . OY.I • ( O.OY.J I C O.OY.J I I C o.o;o
0
0
.I::
""
.I::
Table 3 (cont. )
PATIENT COUNT NAXIHUN TENPERAT\JIIES
REC0t18INANT HEPATITIS 8 VACCINE
STUDT 0816
TREATI1ENT
LOT HUt11!ER CK446
DOSE 111 t1C6
PATIENT CLA!JSt HEALTH CARE PERSOHHE L
I TOTAL VACCIHEES f 8 PATIENTS)· DOSE 2 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I NUMBER
1---------------------------------------------------------------------------------------I
NAX TEHPERATURE
IDEGF,ORALI
••...................... I
,
I
O
.......... I
,
I
1 I
•
2
..................... I
,
I
J
.......... I
, • I 5
.....................
I I
I
, I
..........•..........
I
,
I
WITH
I HAXTEt1P
..........
HO!!HAL I J I J I J I J • 3 • S I I S
I I l7.5l0 I I 37.5:0 I I 37.51.) I I '37.5Y.I I I 37.SY.I I I 37.SY.J I I ( 37.s;o
I I I I I I I I
< 99 I 5 I s I s I 5 I s I s I I s
I I 62.SlO I I u.s;o I I 62.5l0 • ( 6Z.5i'.I • C 6t.5Y.I I l 6Z.5i0 • I I 62.SiO
--------- ·--------------t----------l----------l---------l----------l----------l----------1---------------------1
TEH!'tRAnJRE TAKEN I 8 I 8 I 8 I 8 I 8 I 8 I I -----------
8
I 1100.0:0 I 1100.01.1 I 1100.0Y.) I 1100.0lO I 1100.0Y.J I UOO.OiO I • 1100.0;0
------------------------t----------l---------l----------l----------
TEHPERATURE HOT TAKEN I I I O I O I . 0 Il----------l----------1
D I I I ---------------------1-----------
I I
I I o.oY.1 I I o.ox1 I < o.o;o I , o.o;o I I o.o;o I I o.ox, I I 1 ' o.o;o
0
0
.r:::
~
I.II
Table 3 (cont.)
PATIENT COUNT HAXIHUH TENPERAT\JRES
IIEC0118INANT HEPATIT~S B VACCINE
STUOY 01116
TRUTH£NT
LOT NtlmEII CK446
DOSE 10 t1C&
PATIENT CLASS HE Alllt CARE ptRS~El
I TOTAL YACCINEES f 6 PATIEHTSI - DOSE 3 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUNBEII
NAX TEHPEIIATUIIE
10EG F, M ALI
1---------------------------------------------------------------------------------------I
I O I 1 • 2 I 3 I 4 I 5 • •
Wlllt
I NAX TENP
······················••l••-····••l••···-···•···················••l••······••l••······••l••·················••IP••·······
I I • I I I I I
NOl!l1AL I z I z • I! • I! I I! • 2 I I 2
I I 33.31.1 I I JJ . 3:'-1 I t 33.31.1 I I 33.31. 1 I I 33.37.1 I l 33.3?.l I I l 33.3i0
I I I I • I • I
<99 I "I 4 • "I 4 I 4 I 4 I I 4
I l 66. 77.1 I f 66. 7i0 • f 66. T.I. I I f 66, 77. I I I 66 . 7;0 I ( 66. 7i0 I I ( 66. 7X I
------------------------l----------l----------•----------
TH'IPEIIATUIIE TAKEN I 6 I 6 • 6
l----------t----------1----------1---------------------l------·----
I 6 I 6 I 6 I I 6
I noa.07.1 I 1100.01., • U00.07.) I 1100 . 0;:1 I 1100.0;0 I 1100.01.1 I I 1100 . 0:0
------------------------l----------
n MPEIIATUIIE NOT TAKEN I O Il----------l----------l----------l----------1----------1---------------------l-----------
O • O • O • O I O I I O
I l 0,01.) I I o .o;o I l o.or., I I 1.01.1 I ( 0.01.1 I f 0.07.1 • I I 0,07.l
0
0
&:
1H
0-
STUDY 834
00437

Study 834

serologic markers.
VACCINE: Yeast RecOfllbinant Hepatitis 8 vaccine

PRINCIPAL Mario Rizzetto, M.D.

INVESTIGATOR: Oivision of Gastroenterology
Molinette Hospital
Turin, ITALY
SECONDARY Caterina Canavese, ~.D.

INVESTIGATORS: P1ero Stratta, M.O.
Ferruccio Bonino, M.D.
Molinette Hospital
Turin, ITALY
STUDY LOCATION: Molinette Hospital

Turin' ITALY
DATE STUDY INITIATED: August, 1985
DATE STUDY COMPLETED: In progress.
STUDY POPULATION: The study population consists of 25-30 health care

who are negative for HBsAg, anti-HBc and anti-HBs,
have a normal ALT level and have not previously

HBsAg) intramuscular injection of vaccine at 0, 1, and
and any local or systemic co11plaints for five days
30461/1
1 /15/86
0(1438
-2-
STUDY PROCEDURE: A blood sample is obtained from each study part1c1pant

{Cont.) approximately two weeks before the first injection of
vaccine. Post-vaccination blood samples are obtained
at 1, 2, 3, 6, 8, 12 and 24 months.
All serum samples are assayed for HBsAg . anti-HBc,

anti-HBs, and ALT. Samples may be tested for yeast
~25 mIU/ml may be tested to determine anti-! and
anti-& subtype specificity.

10 mcg lot 979/C-K564 at 0, 1, and 6 months
Injection No.
_1_ L ...1...
25 0 0
Serologic data are not presently available.
Clinical follow-up data are not yet available.

No serious or alarming adverse experiences
attributable to vaccine have been reported.
REACTION POSSIBLY RELATED TO VACCINE

A 40 year-old female developed a •few ecchymotic flat
lesions on the lateral aspect of her breasts,
bi laterally• four days after the first injection of
vaccine. Over the following two days, the lesions
increased, the next day vomiting occurred. All
symptoms disappeared over the next 36 hours and the
subject has remained wel 1. There was no fever. WBC,
hemoglobin, platelets, and coagulation profile were
nonnal. The patient has no history of allergies to
exogenous substances. No .further vacc 1ne was
administered to this patient.
30461/2
1 /15/86
STUDY 835
00438-A
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepat1t1s B Vaccine ,

Study 835
PURPOSE: To evaluate antibody and cl1n1cal responses to yeast

recombinant hepat1t1s B vaccine among health care
serolog1c markers.

Lot 979/C-K564
PRIMARY Stanley J.1 . Lemon , 14 .D.

INVESTIGATOR: Division of Infectious Disease
547 Burnett-WorAack Clinical Sciences Bldg. 229H
University of North Carolina School of Medicine
Chapel Hill, North Carolina 2751 4
SECONDARY Jack T. Stapleton, M.D.

INVESTIGATOR: Division of Infectious Diseases
547 Burnett-Womack Clinical Sciences Bldg. 229H
University of North Carolina School of Medicine
Chapel Hill, North Carolina 27514
STUDY LOCATION: The University of North Carolina School of Medicine

North Carolina Memorial Hospital
Chapel Hill, North Carolina 27514
DATE STUDY INITIATED: October 26, 1984
STUDY POPULATION: The study population consists of 25- 30 health care

personnel of either sex (excluding pregnant women) ,
who are negative for HBsAg , anti-HBc and ant1-HBs,
have a norrAal ALT level and have not previously
received any hepat1t1s B vaccine.
24761/1
1/15/86
Study 835
STUDY PROCEDURE: Eligible study participants receive a 1 .0 ml (10 mcg

HBsAg) intramuscular injection of vaccine at 0, 1
and 6 ruonths. Vaccine rec1pients record their
temperatures and any local or systemic complaints
for five days after each injection of vaccine.
A blood sample 1s obtained from each study
participant approximately two weeks before and on
the day of the first injection of vaccine.
Post-vaccination blood samples are obtained at 1, 2,
3, 6, 8, 12 and 24 110nths.
ant1-HBs, and ALT. Samples may be tested for yeast
titer > 25 mIU/ml may be tested to determine anti-a
and anti-~ type specificity. -
10 mcg Lot 979/C-K564 at 0, l, and 6 months
Injection No.
_ l_ __2_ __3_
29 29 23
Two persons initially anti-HBs positive received

vaccine. One subject displayed a marked boost
in titer after one injection of vaccine. The
other subject developed a protective level of
antibody (~10 mIU/ml) by 10 months
post-vaccination.
2. Serolo9ic Results:
Serologic data at 7-9 months are available for
19 study participants. At 7-9 months, 100%
(19/19) of vaccine recipients seroconverted
(S/N ~2.1) and developed protective levels of
anti-HBs (mlU/ml ~10). The GMT for all
vaccinees and responders (S/N ~2 .1 and
>10 mIU/ml) was 560.9 mIU/ml at that time.
Anti-HBs responses at 1 through 7-9 months are
included in Table 1.
24761/2
l /15/86
Study 835
RESULTS: (Cont.) 3. Clinical Results:

study participants following the first
injection, 25 participants following the second,
and for 23 participants following the third
injection of vaccine. Clinical complaints and
maxi11um temperatures are provided in Tables 2
and 3. In sunnary: ·
Clinical %Frequency by Injection No.

"omnlaint -~1- 2 3
Injection Site 27(7/26) 28(7/25) 30(7/23)
Systemic 23(6/26) 16(4/25) 13(3/23)
Ho serious or alanning adverse reactions

24761/3
1/15/86
Table 1
AHTIBOO'f' RESPOHSES FOLLOWING VACCINATION WITH RECOIIBIHAHT HEPATITIS B VACCitlE
STUDY 0835
POPULATION HEALTH CARI: PERSOHllEL
DOSE 10 tlCG
LOT CK564
REGIMEN O, l, AHO 6 MONTHS
INITIAL SEROlOGY: NEGATIVE
I ;: MITH AHTI-HBS I GMT I 11IU/11LI I

l---------------------------------------1--·--------------------------------------------------I
I I I RESPOtlOERS I
Tlttt:
IMOIITHSI
l---------------------------------------l-----------------1-----------------------------------I
I SIN >= 2. l I tllU/HL >= 10 I All 1/ACCIUEES I S/H >= 2 . 1 I NIU/NL >= 10 I
·--·····················•***••····-·············-····················································~---·········~
I
1 MOttTH I 30X 18/271 I lSX (4/271 I 0.9 I 13 . 9 I 77 . 2
I I I I I
2 MOUTHS I 73X 119/261 I 42X I 11/261 I 7. 2 I 23.2 I 89 . l
I I I I I
3 MOIITHS I 83;1, 15/&I I 67X (4/1,1 I 25.3 I 61.5 I 103 . 6
I I I I I
6 MONTHS I 951. (18/191 I 89% 117/191 I 38.4 I 50.2 I 57 . 1
I I I I I
7/9 tlOlfTHS I 100;: 119/191 I 100% 119/191 I 560 . 9 I 560.9 I 560 . 9
I
**•••*••··········································································································
0
0
-
l:>
&it
-
Table 2
PATIENT COUff CLINICAL COl1PLAIHTS
RECON81HAHT HEPATITIS B VACCIHE
STUDY 0835
TIU ATl1ENT
LOT NUMBER C1<564
DOSE 10 11CG
I TOTH VACCINEES I 29 PATIEHTSI - DOSE 1 I

l----------------------------------------------------------------------------1
CLINICAL
conPLAINTS
l----------------------------------------------------------------------------1
I o I 1 I 2 I 3 I 4 I s •
WITH
l t0t1PL AIHTS
•••••••••••••••-••••••••••••••••••l••••••••••l••••••••••l•••••••••• l••••••••••l•••••••••••••••••••••••••••••••• I••••••••••
I I • I I I I I
RE ACTION, LOCAL (INJECT. SITEI I 6 I l I 3 I l I O I O I I 7
I I Zl.1%1 I I 11.5%1 I I 11,5%1 I I 3.8?.I I I 0 . 01.1 I I 0 . 01.1 I I I Z6 . 9%1
-----------------------------------1
soRENEss I
----------l----------l----------l----------l----------l----------l----------
s I l I l I 1 I o I o I
l-----------
I 1
I 1 1,.21.1 I 1 11.sY.1 I 1 11.sr.1 I c 1.er.1 I I o.or.1 I t 0.01.1 I I ·1 Z6 . 9%J
I I I I I I I I
mn!BHESS I l I o I o I O I o I o I I 1
I , 3.er.1 I 1 0.0;1,1 • 1 o.or.1 I c o.or.1 I I o.or.1 I I o.ox1 • • 1 3.8%1
-----------------------------------•----------l----------l----------l----------l
sYsTE11rc I 3 I l I 1 I 1 I
----------•----------
2 I 2
l----------l-----------
I • 6
I I U.5%1 I I 3 , 8%1 I I 3.87.1 I I 3.87.l I I 7,7Y.I I I 7.7½1 I I I 23.lY.I
-------------------------------------------------------------------------------
I
--------------------- ----------------------
I
WHOLE BOUY/GENERAL I l l I 0 l l 1 I 4
( 3.8Y.I I 1.8:0 I , 0.0%1 I 3.8%) I 1.er.1 I 3.81.I I 1 15 . 4%1
I I
CHILLS I 1 0 I 0 0 0 0 I l
3,8%1 ( 0 .0%1 I I 0.07.J I 0 . 0iO ( o.or., I o.or., I I 3. 8%)
I I
HEADACHE I 0 l 0 l 1 1 I l
o.o,:, ( 3.8½1 I 0.0% I ( 3 . 8)0 I 3.e;o ( J.&r.J I I 11.SY. J
I
RESPI RATORY I 0 0 0 0 1 1 I l
0 . 0%) I o. or., I 0.0%1 I 0 . 01.J I l . 8XI ( :s.er. , I I 3 . 87.I
RHINITIS 0 0 0 I 0 I 0 I 1 I I l
• o.o;o C 0 . 01.) I 0.0iO I ( o.o;o I 1 o.o;o I 1 3.8ZJ I I I J .8Y.I
I I I I I
PHARYHGITIS ISORE TIIROAT J I 0 0 0 I 0 I 1 I 0 I I l
0.0)0 I 0.0% I I o.o;o I 1 0.0iO I I ,.e:o I 1 o.or.1 I I I 3. 8%1
I I I I I
UPPER RESPIR ATORY INFECT., NOS I 0 0 0 I 0 I 0 I 1 I I l
I 0.0% ) I 0 . 0%) I C.0%1 I I O.OiO I f o.or., I 1 3.er. , I I I J. 8%1
I I I I I
11USCULOSl<ELETAL I 2 0 0 I 1 I 0 I 0 I I z
( 7. 7Y. l ( 0.0%) I o.or., I , 3.e:o I 1 O.O¼J I I 0 .07. I I I I 7.7%1 0
0
C
C
N
.,
Table 2 (cont.)
PATIENT COUNT CLUIIC.lL COMPUIIITS
RECOtBINANT HEPATITIS B VACCIUE
STUDY 0835
TRE.lTt1f.NT
LOT IIUl1BEA CK564
DOSE 10 t1CG
--- - - --------------------------------------------------------------------------------------------------------
I TOTAL VACCitlEES ' l9 PUIEtrrs I - DOSE l I
l------------------------------
I
·---------------------------------------------1I tlUlfflER
CLINICAL
COt1PUINTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I l I It I 5 I
MITH
ICCltfPUINTS
•••••••••••••••••••••••••••••••••••!•••••••••• •••••••••• •••••••••• ••••••••••l••••••••••I•••••••••• •••••••••• ••••••••••
I I I
ARTliRALGI.l, t10tlOARTlCULAR I l O O O I O I O l
3.e;o I 0.0%1 I 0.0%1 I 0.0%1 I I 0.0Y.I I I O.OY.I I 3.8%1
I I
11YALGIA I l o O 1 I o I o l
l.8%1 I 0.0%1 I 0.0%1 f 3.8%1 I I 0.0%1 t 0.0%1 I 3.11%1
I
NECK P.lIH I l O O O I O O l
3.81!1 I O.Oll ( 0.0%) I 0.0%1 I I 0.0%1 I 0.07.J I 3 . 87.1
I
ORG.lHS Of SPECI.ll SUfSE I O l O O I O O 1
0.0%1 I 3.87.1 I 0.0%1 I D.D7.1 I I 0.07.J I 0.0%1 I l . 8%1
I
EARACHE I O l I O D I a o l
O.O:O I 3.8%1 I ( O.D7.1 I O.D7.1 I I o.o:o I 0.0%1 I l.8%1
I I
PSYCHI.lTRICIBEHAVIORAL I O O I l O I O O l
I 0.0%1 f I 0.0%1 I I l.8%1 I D.07.1 I I O.DY.II I o.o:o I l.8Y.I
I I I I
IRIHTASIUTY I O I O I l a I O I O 1
I ( o.o:o I I 0.0%1 I I 3.8%) I 0.07.t I I o.o:o I I o.o;o I l.8Y.t
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOtts WITH COHPLAIHTS I 8 I '+ I '+ I 2 I 2 I 2 I I 12
I , 30.8Y.I I I 15.47.1 I I 15.41!1 I 1 7. 77.1 I I 7. 77.1 I I 7. 7Y.I I I I 46.2%1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEASOtts WITH HO COt1Pl.lINTS I 18 I 22 I 22 I 24 I 24 I 24 I I 14
I I 69.2;0 I I 84,6i0 I I 84.6i0 I I 92,37.l I I 92.31.1 I 1 92.37.1 I I I 51.87.J
-----------------------------------l----------1----------1----------1----------l----------l----------1----------I-----------
PERsotis WITH NO DAT.l I D I D I o I o I o I o I I o
I I 0.0%1 I I o·.o;:1 I I O.OiO I I 0 . 0%1 I I 0.0%1 I I o.ox, I I I o.o:o
0
0
~
b
., ""'
Table 2 (cont.)
PATIEHT COUNT CLINICAL COMPLAINTS
REC0118INAHT HEPATITIS 8 VACCIHE
STUDY 0815
TREATHWT
LOT NUt1DER CK564
DOSE 10 tlCG
PATIENT CLASS HEALTH CARE PfRSONHEL
• TOTAL VACCIHEES I 29 PATIENTS I - DOSE 2 I

1----------------------------------------------------------------------------I
I DA'fS POST VACCIHATION • tM1BER
CLINICAL
COHPUIHTS
1----------------------------------------------------------------------------I
I O • l I Z I 3 I 4 I 5 I
WllH
ICOIPLAIHTS
••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••••••••••••• l•••••••••• I•••••••••••••••••••••••~••••••••
• • I I I I I •
RE ACTION, LOCAL IIHJECT. SITU • 4 I It . • Z • 0 I O I O I • 7
I I 16 • OY. I I I U,. 07. I I , 8, 07.1 I l O. 11% l I I O. 07.1 I l O. 07. I I I I 28, 07. I
-----------------------------------1----------
PAIN • Z
----------
l
----------
l
----------1----------
O I O
----------
O
---------- -----------
3
8.07.1 I llt ,07.1 I 4.07.1 I 0.0%1 I I 0 . 0%1 I o .o;o I 12 . 07.1
I
S~EHESS I 2 It l O I O O 5
8.o;o , 16.0% 1 1 4.07.1 1 0.0%1 I 1 0.0%1 1 0 . 01.1 1 zo.07.1
I
TfNOERHESS I l O O O I O O 1
4.07.J t o.o;o t o.o;o I o.ox1 I 1 0.0%1 1 o,o;o , <t.07.1
I
ERYTHrrtA (REDNESS! • 1 O O O I O O l
4.0%1 I 0.07.1 I 0.07.I I 0.07.1 I I o.o;o I 0 . 07.1 I lt . o;o
I
PRURJTIS ( ITCHING I I O Z O O I O O Z
I 1 0.0%1 I 8.07.1 I l o.07.1 I o.ox1 I I o . or.1 I o . or.1 I • < 8 . 0%1
-----------------------------------1
srsTENIC •
----------l----------l----------l----------l----------l----------l----------l-----------
o I 2 I o • o I 1 I 2 • I ti
I I 0.07.J I I 8.07.1 I I 0.07. 1 I I 0.0%1 I I 4 . 0XI I I 8 . 07.1 • • I 16.07.1
--------------------------------·----------------------
I
WHOLE BOOT/GENERAL 0 l 0 0 I 1 1 • 2
• 0 .07.1 ( ft . 0%1 I o. 0% I 0 . 0?.I I I 4.0%1 ( 4 . o;o •I I !I.Or.I
I I
FATIGUEl'WEAl<UESS I 0 1 0 0 I 0 0 l
I o.o;o ( 4. OX I ( O. 07.1 O.OY.I • I 0.07.1 ( 0.07.1 •
I '
-. . o;o
I
NALAISE I D l 0 0 I 1 1 •I 2
o.o;o I lt . 0%1 I o.or., o.OXI I I 4 . 07.1 ( 4 . 07.1 I C 8.07.1
II ' I I
INfECTIOUS 5TNDROt1ES I 0 a 0 0 .I l 0 I 1
I c 0.0%1 I 0.0%1 0.07.1 o.or.1 I t 4 . 0il.J I 0.0::1 4 . 07.)
VIRAL UlffCTION, HOS

I
I 0 0
' 0 0
I
l 0
I '
• l
o.o:o ( 0.0%1 I o. Or. I o.OY. I I I• lt.0iO ( o.oz, •I ' lt . 07.I 0
0
&>
&>
&>
,,
Table 2 (cont. )
RECOl191NAtlT HEPATITIS B VACCIHE
STUDY 0835
TREATttEHT
LOT ~M18ER CK564
DOSE 10 t1CG
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES I 29 PATIEHTSI - DOSE 2 I
1------------------------------------------------· ---------------------------1
I DAYS POST VACCINATION I HUt1BER
CLINICAL l----------------------------------------------------------------------------1 NITH
Cot1PLA INTS I 0 I l I 2 I l I 4 I s I ICOMPLAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••I•••••••••• •••••••••• •••••••••• •••••••••• •••••••••• ••••••••••la•a•••••••
I
JHTEGUflENTAIIY SYSTEl'I I 0 l 0 0 0 0 I l
O.OY.I ( 4.o::o ( 0.07.1 ( o.o,o O.OiO ( O.OY.I I 4.0Y.I
RASH, NOS I 0 1 0 0
' 0 0
I
I
I
1
O.OY.J ( 4.0Y.I 0.0%1 ( O.OY.I 0.0;:1 0.07.1 4.0Y.I
' '
(
II '
RESPIRATORY I 0 0 0 0 0 1 I l
0.0;:1 O.OY.I ( O.OZI ( 0.0;:1 t o.o::o 4.07.1 I I 4.0Y.I
RHINITIS 0
' 0 0 0 0
' 1
I
I 1
( 0. 07. I O.OY.I ( 0.0%1 ( 0.0;() o.o::o 4.ox1 I 4.07.l
PHARYNGITIS ISOIIE lllROATI 0

' 0 0 0
' 0
' 1
' 1
t 0.07.1 I a.or., I o.o::o ( o.o::o ( 0.07.1 ( ft.DY.I ( 4.07.1
tflJSCULOSKELETAL 0 0 0 0 1 1 l
0. OY.I I 0.0;:1 t 0.07.1 o.o::o
l'IYALGIA
' D 0 0
' 0
t 4.0Y.I
1
( 4. 07.,
l
I 4.07.1
1
( 0. 07. J ( D.DiO t 0.0%) ( o.o;:, ( 4.07.1 4,07.) 4.DiO
DIGESTIVE SYSTEl'I 0 1 0 0 0
' D
' 1
( D.OY.I 4.0)() C 0.0)() C 0.0%) ( o.o:o t 0.07.1 I 4 . 0Y.J
AeOOHINAL PAIHS/CRAttPS 0
' l 0 D 0 0 l
o.o::o ( 4,0)(1 0.07.1 0 .DY.I
DIARRHEA
' 0 1
' 0
' 0. OY. I
D
(
0
' G. OY. I
0
( 4.0iO
1
0.0)(1 ( 4.07.1 ( o.o:;o I 0.0;:1 ( 0.0)(1 r o.or.1 ( 4.07.1
NAUSEA I o I 1 I o I o I o I o I I l
I f 0.07.1 I I 4.07.I I I o.ox, I I O.OY.I I f 0.0;:1 I I 0.0;() I I I 4.01.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsotis MITH COMPLAIHTS I 4 I 6 I 2 I O I 1 I 2 I I 9
I f 16.o;o I I 24.0Y.l .I I 8.0Y.I I I o.o;o I ( 4.07.I I I fl.OX) I I I 36.0iO
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I----------- 0
PERSOt1s MITH uo COMPLAINTS I n I n I ZJ I 25 I z4 I ZJ · I I 16 0
I f 8't.OY.I I I 76.0Y.I I t 92.0Y.I I 1100.0?.I I I 96.0?.I I I n.o;n I I I 64.0Y.l ~
~
IJ'I
.,
Table 2 (cont.)
PATI EITT COUHf CLIHICAL COHPLAINTS
RECOt18IHANT HEPATITIS 8 VACCII-IE
STUDY 0835
TREATMENT
LOT tM'IBER CKS64
IIOSE 10 HCG
PATIENT cu ss: HE ALTH CARE PERSOMfE L
I TOTAL VACCIHEf:S I Z9 PATIENTS) - DOSI! Z I

•----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUHBER
CLINICAL
COHPL AIHrs
1
•
----------------------------------------------------------------------------•
0 I 1 I 2 I 3 • 4 • 5 •
WITH
ltot1PLAIHTS
••••••••••••••••••••••••••••••••-•••••••••••••••••••••••••••••••••• l•••••••••• •••••••••••I••••••••••••••••••••• •••••••••••
-----------------------------------•----------1----------•
PERSONS WITH HO DATA • l I l I
----------1----------
1 I 1
•----------1----------1----------1-----------
I l I 1 • I l
I C 'S . 8i!I I C 3.8i!I I I 3.8i!I I ( 3.8i!I I I 3 , 8i!I I I 3.87.1 • • I 3.8i!I
0
0
,.
4:>
,,, ""
Table 2 (cont. )
PATIENT C~T CLINICAL Cot'IPLAIHTS
RECOt1BINAHT HEPATITIS 8 VACCINE
STUDY l!8l5
TREATt1ENT
LOT IMIBER Cl<S64
DOSE 10 MCC.
I TOTAL YACCitlEES I 23 PATIEHTSI - DOSE 3 •

1----------------------------------------------------------------------------•
I DAYS POST YACCIIIATIOH I HUMBER
1----------------------------------------------------------------------------•
CLINICAL
COtlPUIHTS
................................... I
, O • l
..........•..........
• I
I 2
.......... I 3
,
..........
I
I 4
.......... I
,
I
5
.......... I
, WITH
ICDMPUIHTS
......•...•.........•
I
,
I
,
I •
REACTION, LOCAL lltUECT. SITEI I 6 I ft I 2 I 1 I l I o • I 7
I c 26.UO I l 17.47.1 I l 11. 77.I I c 4. 37.1 I c 4.37.1 I I 0.07.1 I I I 30,47.1
-----------------------------------,----------
PAIH OH INJECTION I l
----------
0
----------
0
----------
0
----------
0
----------
0
---------- -----------
l
I c 4.37.1 I 0.07.) C 0.07.) C 0,07.) I 0.07. J i 0.07.) I 4. 37. I
I
SORENESS I 6 3 2 1 l 0 6
I C 26.17.) ( 13,0XI ( (1.77.) C 't.37.) C 4.37.1 ( O.OXI C 26.17.1
I
ERYTHEl1A CREOtlESSI I 0
0.0¼1 (
1
4.37.1 C 0.07.J
0
•
C O.D7.I I
0
0.0%)
0
o.o;o (
1
4.37.)
'
SWELLIHG I 0
0.07.) (
l
4.3i0 ·, 0
O.OXI C O.OiO• I
0
o.o;o I
0
o.o;o I
l
4. lY. I
l'RURITIS UTCHIHGJ I o I 1 I o I a I o I o I I 1
I C 0.07.1 I ( 4.3Y.I I C o.ax, I I o.ax, I I O.OXI I I O.OY.I I I I 4.3?.J
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
svsn111c I o • t • a I o I o I 1 I I 3
I C o. 07. l I l II. 7Y. I I C O. 0% I I I O. OY. I I I O. OY. I I I 4. lY. I I I I 13 . 07. I
I
WHOLE BOOY/GEHERAL I a 1 0 0 0 I 0 I l
a.ox, I 4.37.) I O. IIY. I I 0. IIY. I I 0.07.) I I O.OiO •I I I 4.37.)
I I I
CHILLS I a
0.07.)
l
4.3%) •
0 .117.)
0 0 I
O.OY.I I I
0 I
o.o;o I
I
I
1
' '
I O.OY.I
' I
I 4.37.1
FLUSH I 0
0.07.J
1
( •
0.07.) I
0
0.01.)
D I
I
0 I
o.or.1 I
I l
4.37.)
RESPIRATORY 0
' 4.3i0
0 D 0
I 0.01.1
a
I
I
I
1 I•
• I
I
I 1
• O.OiO I 0.0%) ( 0.0%) I 0.0)0 I a.ox, I 1 4.1;0 I • I 4.JiO
I I
RHINITIS I 0 0 0 0 0 I l • I l
I o.o;o I 0 .OY.I C 0 .01.) I 0.0,0 ( o. OY.I I I 4.3%1 I • .I I 4.3i0 0
,.
0
...,,.
,
Table 2 (cont.)
PATIENT COUHT CLINICAL COHPLAINTS
RECONBIIIAtlT HEPATITIS B VACCINE
STUDY 0835
TREATHENT
LOT NutlBER Ck564
DOSE 10 MCG
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I 23 PATIENTS I - DOSE 3 I
l----------------------------------------------------------------------------1
CLINICAL 1----------------------------------------------------------------------------I MITH
COtfPUINTS I O I 1 I 2 I 3 I 4 I S I ICOMPLAINTS
•••••••••••••••••••••••••••••••••••l•••••••••• l••••••••••l••••••••••I•••••••••• ••••••••••!•••••••••• ••••••••••!••••••••••
I
UPPER RESPIRATORY INFECT., NOS I 0 I 0 I 0 I 0 0 1 1
I t O.OY.I I I o.o;o I c O.OY.l I C O.OY.I ( 0-.0Y.J 4. 3Y.I
'
4.3:'.I
(
I I I I
DIGESTIVE SYSTE~ I 0 I l I D I 0 0
I c o.oio I c 4.1;:1 I c O,DY.I I C 0,0¼1 ( I.OY.I I O.OY.I
l
I 4.3Y.I
•
I I I I
DIARRHEA I 0 I l I 0 I 0 0 0 1
I I O.OY.I I C 4. lY.I I C 0.0%1 I I 0.0%) ( I.DY.I I 4. 3Y. I
ORGANS OF SPECIAL SENSE

I
I 0
I
I l
I
I 0
I
I 0 0
' 0
0.0%1
l
O.OY.I I C 4.1;:1 I c 0.0%1 I c O.OY.I ( o.o::o 0.0;1.1 4.3Y.I
EYES, BURHitlG I o I l I o I o I o I
' o I I
' 1
I C 0.0%1 I I 4.3¼1 I I O.OY.l I I O.OY.I I I O.OY.I I I O.OY.I I I I 4.3Y.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS MITH Cot1PUIHTS I 6 I 5 I 2 I l I l I l I I 7
I C 26.lY.I I I 21, 7Y.) I C 8.7:0 I f 4.3)0 I f 4.3Y.I I I 4.3:1.1 I I C J0.4ZI
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I----------
PERSotlS MI TH NO cOt1PLAn1rs I 11 I 1a I n I 22 I 22 I 22 I I 16
I ( 71,9;0 I I 78.JY.I I C 91.]Zl I C 95.77.1 I I 9!;.7Y.I I ( 95.77.J I I I fo9.6Y.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEASOtlS WITH NO DATA I O I O I O I O I O I O I I 0
I I O.OY.I I I O,OY.) I C O.OY.) I I o.or.1 I ( O.OY.I I C O.OY.I I I C o.or.,
0
0
&,
~
(J>
-
Table 3
PATIENT COUNT HAXltlJII TEHPERATUAES
RECOl18INANT HEPATITIS B VACCINE
STUDY D835
TRE ATNEHT
LOT Nllt18ER CK564
DOSE 10 t1CG
PATI ENT CLASS: HEALTH CARE PERS~ l
I TOTAL VACCl NEES I 29 PATlEHTSI - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DA'rS POST VACClHATiotl I NUM8ER
NAX Tlt1PERATURE
(D[G f , tmALI
l---------------------------------------------------------------------------------------1
I O I 1 I t I l I 4 I 5 I I
MITH
I HAX TEHP
•••••••••••••••••••••••• l•••••••••• l•••••••••• I•••••••••• •••••••••• •••••••••••••••••••••••••••••• I•••••••••• ••••••••••
HORNAL I t I 2 I 2 2 2 2 2
e.o;o I c e.0%1 I , a.0%1 c e.o:o , 8. 1?.1 1 8.1?.1 , e.0:1.1
I I
< 99 I 19 I ti I u 2D 19 n 1s
76.0%1 I C 8 4.0%) I I 80.0%1 C eo.01.1 I 79 . 2%1 I 82.6%) I ,60.0%1
I I
99 - 99. 9 I ,. I 2 I 3 1 1 2 s
16.0lO I C 8.0?.J I I lt . 0%1 C 4.07.1 I <t.2%1 I 8 .7iO I t0.0%1
I I
100 - 100. 9 I o I o I o t t o 3
I I 0.0%1 I C o . OlO I I 0.01.1 I t e.01.1 I e.3?.J I o.oio I I 12 . 0;0
------------------------l---~------l----------
TEMPERATI.mE TAKEN I 25 I 25
l----------l----------t----------1----------1---------------------I-----------
I 25 I 25 I 24 I 23 I I 25
I t 86.2%1 I t 86 . 2%1 I t 86.21.1 I t 86.21.1 I t 82.11%1 I t 79.3%1 I I 1 86 . 2%1
------------------------l----------
TEMPEHTURE HOT TAKEN I 4
l----------l----------t----------l----------l----------1
I 4 I 4 I 4 I 5 I 6 I
---------------------1-----------
I 4
I I ll.8lO I I 13,BiO I I 13.87.l I I 13.8Y.I I I 17,2%1 I I 2D.7lO I I I 13.8%1
C)
0
C
.c
,0
Table 3 (amt.)
PATIENT COUNT HAXIHLN TEHPERATURES
RECOttBINANT HEPATITIS 8 VACCINE
STUOY 0835
TilEATHENT
LOT NU1BER CK564
DOSE 10 l'ICG
I TOTAL YACCINEES I 29 PATIENTS) - DOSE 2 •

1---------------------------------------------------------------------------------------I
HAX TEMPERATURE
(DEG F, ORAU
l---------------------------------------------------------------------------------------1
I O I l I 2 I J I 4 • 5 I I
WITH
I HAX TEMP
··········••D••·····························••I••········
I
.............................. ·····················•~·········
•
NORMAL • l • l I l l l l • l
4.o;o I I 4.0)0 I ( 4.3)0 C 4.2¼1 ( 4.2¼1 I 4.3)0 I I 4.0¼1
< 99 I 2t
•I 19
II ia 20 n n •• 15
eo.o:o I I 76.0lO • I 78.3)0 C 83.V.I I 87.5¼1 I 82.6)0 I I 60.0¼)
I I I
99 - 99. 9 I 4 I 4 I 4 3 2 3 I a
16, OY. I I I 16. 0?. II I 17. 47. I I 12. 51.1 I 8. 37. I I 13. ox I I I 32 • 01. I
103 - 103. 9 • O I• l II o o o o
•I l
I ( 0.0?.I • I 4.0?.) I C 0.07.I I 0.0¼1 I o,o;o t 0.0XI I C 4.0?.I
------------------------l----------l----------l----------l----------1----------t----------1---------------------1-----------
TEHPERATURE TAKEN I 25 I 25 I 23 I 24 I 24 I 23 I I 25
I c 86.uo I I e6.2;0 I 1 79.37.1 • c e2.a:o I I e2.ar.1 • c 79,3,.1 I I 1 86.21.1
------------------------•----------l----------l----------l----------l----------1----------1---------------------I-----------
TEMPERATURE NOT TAKEN I 4 I 4 I 6 • 5 I 5 I 6 I I 4
• c n.e;o I I n.ax, I 1 20.r/.1 • 1 11.2;0 I c 11.2x1 • 1 211.1;0 I I c n.81.1
0
0
.c
\II
0
-
Table 3 (cont. )
PATIENT Cou-lT NAXIHU't TEHP£RATURES
RECOttBINAHT HEPATITIS 8 VACCINE
STUDY 0835
TREATMENT
LOT .ufflER CK564
OOSE 10 tlCG
PATUMT CLASS HEALTH CARE PERSONNEL
I TOTAL VACCIN£ES ( 23 PATIENTSI - DOSE 3 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUt18ER
H•X TENPERATORE
I DEG F, ORAL I
l---------------------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I 5 I I • NA><WITH
lEHP
••••••••••••••••••••••••l••-••••••l••••••••••l••••••••ol•••••••••••••••••••••••••••••••••••••••••••l••••••••••I••••••••••
• • I I I I I I
NOIIHAL I 1 I 1 I 1 • l I 1 I l • I l
I , s.o;o I 1 5.ox, I t 4.8%t • , 5.1%1 I I s.1;O I t s.1x1 • I 1 1t.ex1
I I I I I I I •
< 99 I 17 I u, I 17 I 17 I 16 • u. • I 16
I t 85.0%1 I I 90.0%1 I I
t 81.0%) I
t 89.5iO I l 84.2%1 t 8't.2iO • I t 76.2%1
I I I I I I •
99 - 99. 9 I 2 I 1 I 1 I 1 I 2 I z I •• ,.
I ( 10.0;0 • I 15.0%) I I 14.3%) • I 5.3%1 I ( 10.5%) I I 10.5%1 • I I 19.0%1
-------------------- ·---l----------l----------l----------l----------1----------1----------l------·--------------I-----------
TEHPERATURE TAKEN I U I 20 I 21 • 19 • 19 I 19 I I 21
I ( 87.0%1 • I 87.0%) I ( 91.3%) I I 82.6%1 I I 82.6%) I ( 82.6%) • I I 91.3%1
------------------------l----------l----------l----------•----------l----------l----------1---------------------1-----------
TENPERATURE NOT TAKEN • 3 • 3 • Z I <\ • 4 I <\ I I t
I ( 13.0iO I I n.o:o I ( 8.7:0 f ( 17.4%) I I 17.47.) I I 17.47.) I I I 8.7%1
0
0
J:::
...
I.II
-
004'52
PROGRAl'l: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,

Study 838.

recombinant hepatitis B vaccine in the following ,
initially seronegat1ve, adult populations:
1. Dialysis Patients
2. Predialysis Patients
VACCINE: Yeast Recorab1nant Hepatitis B Vaccine
Lo_t #986/C-K733 ( 20 mcg HBsAg/111)
PRINCIPAL Professor Dr. Friedrich Deinhardt

INVEST! GATOR: Director
Max v. Pettenkofer Institute
Pettenkoferstr. 9a
8000 Muenchen 2
West Gennany
SECONDARY Dr. Wolfgang J1lg

INVESTIGATORS: Max v. Pettenkofer Institute
Pettenkoferstr. 9a
8000 Muenchen 2
West Gennany
Professor Dr. Juergen Bon111er

Med1z1n1sche Un1vers1tatsklinik
Bergheimer Str. 56
6900 Heidelberg 1
West Germany
Professor Dr. R. Mueller
Med1z1n1sche Hochschule Hannover
Abt. f. lnnere Med1z1n
Karl-Wiechert-Allee 9
D-3000 Hannover-Kleefeld
West Germany
Professor Dr. Horst Braas
Staedtische Krankenanstalten
Medizinische Klinik II
Bremserstr. 79
D-6700 Ludw1gshafen
West Genaany
24421/1
1 /3/86
001453
Study 838
SECONDARY Dr. Bernhard Weinel

INVESTIGATORS: Staedtische Krankenanstalten
(Cont.) Med1z1nische K11n1k II
Bre11serstr. 79
D-6700 Ludwigshafen
West 6ermany
STUDY LOCATIONS: unich, Heidelberg , Hannover, and Ludwigshafen,

West Germany
DATE INITIATED: June 7, 1984
STUDY POPULATIONS: Under the or1 gi na 1 protoco 1 and subsequent addenda,

the following groups are enrolled in the study.
Participants may be of either sex, but pregnant WOiien
are excluded. Prospective vaccine recipients must be
negative for hep&tith 8 sero1og1c markers, have a
normal ALT level and may not have received any
hepatitis B vaccine (except as noted under
addendum #2).
Protocol/ Approx.
Addendum , Population Number Regi19en
Initial Health Care 25 10 IIICg (0.5 111)
protocol Personnel at 0, 1, and 6
110nths
In1t1al Dialysis 50 40 IICg (2 X 1.0
pr otocol Patients 111) at o. 1 and
6 111e>nths
Add. #1 Dialysis 20 20 lliCg ( 1.0 ml)
Patients at o. 1, 2, 3, 4,
and 6 raonths
Add. #1 Dialysis 20 40 ntcg (2 x 1.0 ml)
Patients at 0, 1, 2, 3, 4,
and 6 months
\
OOLl54
Study 838
STUDY POPULATIONS: Protocol/ Approx.

(Cont.) Addendum I. Po~ulatton Number Regi!!!in
Add. #2 Initial 10 ~g (0.5 ml)
protocol for health care
subjects who personnel; 40 mcg
do not form (2 x 1.0 Ml) for
antt-HBs dialysis patients
after 3 doses
of vaccine
Add. 03 Pred1alys1s 10 40 mcg (2 x 1.0 ml)
patients at O, 1, and 6
months
PROCEDURE: Participants receive intramuscular 1nject1ons of

vaccine according to the reginiens outlined above under
STUDY POPULATIONS.
Study participants will be asked to record their
temperature for five days after each injection and to
note any local or systeniic COllll)laints.
Serum samples will be obtained prior to and on the day
of vaccination. Follow-up blood spec1aens will be
obtained 1, 2, 3, 6, 8, 12 and 24 months post the
initial injection of vaccine. Nonresponders who
receive a fourth Injection of vaccine under addendu111
#2 will have a blood sample taken one rDOnth after this
injection. Serum saniples w111 be assayed for HBsAg,
ant1-HBs, antt-HBc and ALT by Dr. De1nhardt's
laboratory. SalllJ)les may also be assayed at MSDRL for
yeast antibody. Those th1t are positive for antt-HBs
with a titer of ~25 raIU/111 lllllY be assayed for anti-!
and anti-!l_ subtype specificity.
24421-3
1/3/8&
00455
Study 838

10 •cg Lot #986/C-K733 at 0, 1, and 6 months.
In1ection No.
22 19 17
Serolog1c data are ava1 lab le for 17 participants
at 7/8 months of follow-up. Ninety-four percent
(16/17) of the subjects seroconverted (S/N ~2.1)
and developed protective levels of ant1-HBs
(mIU/ml ~10) at that time. The GMT at 7/8 months
for all vacc1nees was 284.8 mIU/ml and 437 .1 for
responders (alU/ml ~10).
Refer to Table 1 for ant1-HBs responses and GMTs

Clinical follow-up data are available for 22 and
13 participants after injections 1 and 2,
co111pla1nts are presented below.
Type of Frequency in% by InJect1on No.

C0111pl11nt ____,_ 2 _3_
Injection 18(4/22) 8(1/13)

Site
Systemic 27(6/22) 8(1 /13)
Refer to Table 2 for listings of specific cl1n1cal

complaints by inject ton number. Maximum

experiences attributable to vaccine.
24421---4
1 /3/86
Table 1
ANTIBODY RESPONSES FOLLOWING VACCINATION WITH RECOMBINANT HEPATITIS B VACCINE
STUDY 0838
POPULATIOH HEALTH CARE PERSONl~EL
DOSE 10 MCG
LOT CK733
REGIMEN 0, 1, ANO 6 MONTHS
INITIAL SEROLOGl NEGATIVE
I ;( li~,il ANTI-Hr,:; i GMT Ci1JU/11LI I

1---------------------------------------l-----------------------------------------------------1
I I I RESPOIIDERS I
TIME
( MDHTHSI
l---------------------------------------1-----------------I-----------------------------------I
I SIN>= 2.1 I 11IU/11L >; 10 I ALL VACCIHEES I SIN>= 2 . 1 I MIU/ML>= 10 I
I I . I
··········································································································•*·······
I 1 MONTH I 19)( (4/Zl I 9.SX 12/21 1 I 0.6 13.6 43. o
I I I
I 2 t10t1THS I S8Z 111/191 47½ 19/191 I 4.1 21 . 0 39.2
I I I
I 3 MONTHS I 82Z (14/171 71Z 112/171 I 15. 7 36.5 46.9
I I I
I 6 MONTHS I BlY. 110/12 I 8JZ 110/12 I I 26. 9 66 • 2 66. 2
I I I
I 7/8 HOHTHS I 94Z 116/171 94Z 116/171 I 284 . 8 437.l 437.l
I I I
I 10 MONTHS I 10oz 19/9) 100:f. 19/91 I 509.4 S09.4 509.4
I I I I
•••••*•••••••••tHt•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••*•••••••••••••••••••••••••u•••••••
0
0
.c
\JI
0-
-
Table 2
PATIENT COltIT CLINICAL COHPLAIHTS
STUDY 0838
TRUTl1EHT
LOT NUMBER CK733
DOSE 10 NCG
PATIENT CLASS: HEALTH CARE PERS~l
I TOTAL VACCIHEtS I 22 PATUHTSI - DOSE l I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I t-AIHBER
1----------------------------------------------------------------------------I
CLINICAL
COt1PLAIHTS I
,I O I 1 I 2 I
,I
3 I 4 I
,I S I
,I MITH
I COt1PLAIHTS
................................... ..........•.......... .......... .......... .......... .......... ....•..... ..........
•I
,• ,I ,
I
REACTIOM, LOCAL IINJECT. SITEI • " O I l I O I D • 0 I I It
• f 18.2%1 I f o.OY.I I f 4.5:o • f 0.0%1 I 1 0.07.1 • I o.o;o I I 1 18.2%1
-----------------------------------1----------l----------•----------l----------l----------•----------•----------I-----------
PAIH I 1 I o I o I o • o I o I I l
I f 4.5%) I ( 0.0%1 • f 0.0%1 I I 0.0%1 • I O.OY.I I I O.OY.I • I I It.SY.I
SllllfNESS
I
I 3
•
I o
•• o
I
I o
I
I o
II o
I
I
II 3
• ( 13.6%1 I ( 1.0;0 I ( 0.07.1 I I o.o;o • l O.OY.I I ( 0.07.I I I I 11.6%1
SWELLING
•• o
I
• o
I• 1 •
I o
I
I o
•I o
•I II 1
I I 0.0%1 I I 0.0%) I I 4.5%1 I I 0.0%1 I ( O.OY.I I ( 0.0%) I I I 4.5%1
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
svsTEl1It I 2 I 4 • 2 I O I O • 1 • I 6
• I 9.1:0 I ( 18.2:0 • ( 9.Uo I I 0.07.I I I 0.07.1 I f 4.5%1 I I I 27.3%1
---------------------- ·-----------------------------------------------------------------------------------------------------
I
WHOLE BODY/GENERAL I 2 4 Z O O O I I 6
I 9.1?.I ( 18.2?.I I 9.1%1 I 0.07.1 I a.ox, ( O.OXI I I I 27.3?.I
I I
FATIGUE/WEAKNESS I 2 3 l O O O I I 5
9.liO I ll.6Y.I ( 4.5%1 ( 0.0%1 I a.OX) C 0.0%1 I I I ZZ.7XI
I I
HEADACHE I O 1 1 0 O o I I 2
o.o;o I 4.5:'.I I 4.5%1 ( 0.0%1 f O.OXI I O.OXI I I I 9.lXI
I I
DIGESTIVE Sl'STEtf I O O O D D 1 f I l
o.o:o ( 0.01.1 ( 0.11:0 C o.o;o C O.OY.I ( 4.5?.I I I I Ct.5:0
I I
DIARRHEA I O O O O O l I I 1
I c o.o:o I c o.o:o f o.ox1 I 1 0.0%1 I f o.or.1 I l 4.5%1 I I 1 4.s:o
-----------------------------------1----------•----------•----------I----------I----------I----------I----------I-----------
PERSONS MITH CONPUIHTS I 6 • 4 • 3 I O I O • I I I 9
I ( 27.37.) I ( 18.27.) • ( 13.6%1 • f 0.0%) I ( 0.0%) I ( 4.SXI I I I 40.9XI
-----------------------------------•----------l----------l----------l----------1----------1----------1----------I-----------
Pf:RSONS WITH NO COHPLAINTS • 16 I 18 • 19 I 22 I 22 I 21 I I 13
0
• , 12.11., • , 81.8lO • c 8E..1tr.1 I 1100.or.1 I uoo.ox, I f 95.5?.> I • , 59.lY.I 0
&:,
\JI
~
-
Table 2 (cont.)
REC0f1BIHANT HEPATITIS B VACCINE
STUDY CB'J&
TREATt1ENT
LOT NIJ!18ER CK7J3
DOSE 10 MCG
PATIENT CU SS HE ALTH CARE PERSONNEL
I TOTAL VACCINEES I 22 PATIEHTS I - DOSE l I

l----------------------------------------------------------------------------1
CLIHJCAL
COMPLAINTS
1----------------------------------------------------------------------------I
I O I l I 2 I 3 I It I § I
WITH
ICOt1PlAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••••••••••••• l•••••••••• l•••••••••• I•••••••••••••••••••••
-----------------------------------1----------l----------1----------1
PERSOHS WITH HO OAT.A I O I O I D I----------1----------I----------I----------I-----------
O I e I O I I o
I < o. o;o • , o.o;o I I a.oz, I « o.o:o I < o.ox , I c o.oz1 I I , o.o;o
0
0
&:
VI
OD
Table 2 (cont.)
PATIENT COUNT CLINICAL COffl'LAINTS
RECOHB(HANT HEPATITIS B VACCINE
STUDY 08 '58
TREATI1ENT
LOT NUMBER Cl<733
DOSE 10 t1CG
PATIENT CLASS HE ALTH CARE PERSONNEL
I TOTAL VACCINEES ( 13 PATIENTS) - DOSE 2 I

l----------------------------------------------------------------------------1
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I '3 I 4 I 5 \
WITH
ltot1PLAIHTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••
I I I l••••••••••
I l••••••••••l••••••••••l••••••••••I••••••••••
I I I I
REACTION, LOCAL CINJECT . SITE» I l I l I o I O I 0 I 0 I I l
I t 7. 7i0 I I 7.7i0 I ( o.o,o I t 0.01.1 I C o.or.1 I t o.or.1 I I t 7.71.)
-----------------------------------1----------
PAIN • l
I----------I----------I----------I----------I----------I----------I
• 1 I O I O • 0 I O I \
-----------
1
It 1 . 11.1 11 1.11.1 I< o.o;o I< o.o:o I c o.o;o l·t o.o;o I It 1 . 11.,
-----------------------------------l----------l----------1----------l----------l----------•----------l----------l-----------
srsrE11Ic I O I 1 I O I O I O I O I I l
I I 0.01.1 I I 7,7%1 I I O.OZ) I I o . or.1 I t o . or.1 I ( 0. 0%1 I I ( 7 . 77.)
I
!MOLE BOOY/GEHERAL I O I 1 I O I O I O I I I I l
0. o:o I I 7. 7% I I ( 0. 0,0 I I O. o:o I C O. or. I I ( 0. o;o I I ( 7. 71.1
I I I I I I I
FUIGUE~EAKHESS I 0 I l I o I 0 I 0 I 0 I I l
I < o.o:o I 1 1.11.1 I c 0.01.1 I c o.o:o I c o.or., It 0.01.1 I Ic 7.77.1
-----------------------------------•----------•----------l----------l----------•----------•----------1----------1-----------
PERSONS WI TH COMPLAINTS I 1 I 2 I O I O I O I O I I 2
I I 7. 77.1 I I 1 5.'tX) I ( O.OXI I t o.o;o f t O.OX) I ( 0.0%1 I I ( 15.4%)
-----------------------------------1----------l----------l----------l----------•----------•----------•----------I
PERSONS WITH HO COMPLAINTS I 12 I 11 I 13 I 13 I 13 • 13 I I-----------
11
I , 92.31.1 I c &4.61.1 I noo.or., I noo . or.1 I noo.o::o • noo.ox , • I , &4.t,;O
-----------------------------------1----------l----------•----------l----------
PERSONS WITH t10 DATA • O I O I O I O
l----------
• 0
•----------l----------1-----------
I O I I O
• I O.OXI I I 0.01.1 I ( o.o;o I t O. OXI I t 0.0%1 I I O,OX I I I I o.or. 1
0
0
l::
IJ1
-
,0
Table 3
PATIENT COUNT NAXItlUtt TEMPERATURES
REC018INANT HEPATITIS 8 VACCINE
STUDY 0838
TREATHENT
LOT NUl'1BER Ck73l
DOSE 10 ttCG
PATIENT CUSS HEALTH CARE PER~l
• TOTAL VACCINEES I 22 PATIENTS! - DOSE l I

•l---------------------------------------------------------------------------------------1
OATS POST VACCINATION I NUH8ER
•---------------------------------------------------------------------------------------1
NAX TEMPERATURE
I DEG F • ORA U I O I l I 2 • l
....................................................................
I I I I I •
,
I..........•..........•..........•..........
4 I 5 •
I
• I HA><WITH
I
TEHP
•..........
< 99 I 10 I n I 10 I 11 I 9 I 8 I I 9
I ( 90.9"/.) I ( 91.7)0 I ( 90.9:I.) • U00.0:1.1 I I 90.0:I.I • ( 88.9?.) I I ( 75.D%)
• I • I I I I I
99 - 99. 9 I 1 I l I l I O I l • l • I l
• ( 9.llO I C 8.3?.) • I 9.1%) I I o.o;o I I 10.0:I.) • ( 11. l ?.) • I I 25.0%1
------------------------l----------l----------l----------•----------1----------l----------•---------------------I-----------
TEt1PER ATURE TAKEN I 11 I 12 I 11 I 11 I 10 I 9 I I U
I I 50.07.1 I I 54.5lO I c 5o.o;o I I 50.o:o I I 45.5:'-l I I 40.97.l I I I 54.5% 1
------------------------1----------1
TENF'tRATUAE NOT TAKEN I 11 I
----------•----------l----------l----------l----------
10 I 11 I 11 I 12 I U
•---------------------I-----------
I I 10
I I 5o.o;o I I 45.5:t.l I c 50.0::0 • I 50.0:t.l I I 54.5:t.l I I 59.l?.l I • I 45 . 5:o
0
0
~
:.,-
-
0
Table 3 (cont.)
PATIENT COUNT HAXItl.11 TEHPERATURES

RECDl'IBINANT HEPATITIS 8 VACCINE
STUDY I 08~8
TREATnENT
LDT NU1BUP CK733
COSE 10 t1CG
PATIENT CUSS: HEALTH CARE PER~l
I TOTAL Vl CCIHEES I 13 PATIENTSJ - DOSE 2 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUMBER
HAX TEHPERATURE 1 ---------------------------------------------------------------------------------------I WITH
IDEI.F,ORALJ I O I 1 • 2 • 3 • 4
............................................................................... I 5 • •
, . t1AXTEl1P
..........•..........•..........•..........
I I I • I I • •
< 99 • 7 • 7 • 7 • 6 • 6 I 6 • I 7
I (100.0)0 • 1100.0:0 • noo.o;o • (100.DY.I I llD0.GY.I I Cl0D.0Y.I • • n oo .o;o
------------------------ I•----------1----------1----------•----------l----------l----------
TEHPERATURE TAKEN 7 • 7 I 7 I 6 • 6 I 6
•---------------------I-----------
• I 7
I I 53.87.J I I SJ.SY.I I I 53.87.1 • I 46.27.1 • I 46.2%1 I c 46.2%1 • 1 I 53 .9%1
------------------------1
TEHPER ATURE HOT TAKEN •
----------•----------l----------•----------•----------l----------•---------------------I-----------
6 I 6 I 6 I 7 I 7 I 7 I • 6
I I 46.2'0 I t lt6 . 2Y.I • I lt6.2Y.I I I S3 . 9l0 I I 53.87.l I I SJ.SY.I • I I 4t..2l0
0
0
.c
-
0-
STUDY 841
00462
PROGRAM: Alum-Adsorbed Ye.ast Recombinant Hepatitis B Vaccine,

Study 841.
for hepatitis 8 virus serologic markers.

Lot #978/C-K 563 (10 mcg HBsAg/ml}
PRINCIPAL Arie J. Zuckerman. M.O.

INVESTIGATORS: Professor of Microbiology
Director, Department of Medical Microbiology
London School of Hygiene and Tropical Medicine
Keppel Street
London WClE 7HT
United Kingdom
Iain Murray-Lyon, M.D.
Consultant Physician
Charing Cross Hospital
London W.6.
United Kingdom
SECONDARY Dr. John Coleman
INVESTIGATORS: Charing Cross Hospital
London W.6.
United Kingdom
Or. Michael Anderson
London W.6.
United Kingdom
STUDY LOCATION: Charing Cross Hospital

London W.6.
United Kingdom
DATE INITIATED: May 1985.

DATE C0'4PLETED: In progress.
STUDY POPULATION: The study population will consist of 80-100 health
care personnel of either sex (excluding pregnant
women), who are negative for HBsAg, anti-HBc and
anti-HBs, and have not previously received any
hepatitis 8 vaccine.
3107 Ill
12/31/85
00ll63
Study 841
PROCEDURE: Eligible participants will receive a 1.0 ml injection

of vaccine in the deltoid muscle at 0, l, and 6
months. Study participants will be asked to take and
record their temperatures for five days after each
injection of vaccine and to record any local or
systemic complaints that they may have. They will be
asked to notify the study physician 1nmed1ately 1f any
unexpected or serious reaction occurs.
Blood specimens will be obtained prior to and 1, 2, 3,
6, 8, 12, and 24 months fo1 low1ng the first
injection. All samples will be assayed in Dr.
Zuckennan's laboratory for HBsAg, anti-HBc and
anti-HBs. Samples may also be assayed for yeast
antibody and subtype specificity.
RESULTS: Serologic and clinical follow-up data are not

presently available. No serious or alarming adverse
experiences attributable to vaccine have been
31071/2
12/31 /85
O'I
u,
co
►
o
::,
t-
(.t,
r
00464

Study 859
PURPOSE: This study is designed to evaluate antibody and

clinical responses to hepatitis B yeast recombinant
for hepatitis 8 serolog1c markers.

Lot 1978/C-K563 (10mcg HBsAg)
PRINCIPAL Nathan Clumeck, M.D.

INVESTIGATOR: Assistant Department Head
Section of Infectious Diseases
Hospital of St. Pierre
Rue Haute, 322
Brussels, BELGIUM
SECONDARY Pierre Reding, M.D.

INVESTIGATOR: Gastroenterology Service
Hospital St. Pierre
Rue Haute, 322
Brussels, BELGIUM
STUDY LOCATION: Hospital of St. Pierre

Section of Infectious Disease
Department of Internal Medicine
Rue Haute. 322
Brussels, BELGIUM
DATE INITIATED: March 12, 1985
STUDY POPULATION: The study .population will consist of 30 to 50 health

care personnel of either sex (excluding pregnant
women), who are negative for anti-HBc, anti-HBs,
HBsAg, have a normal ALT level and have not previously
received any hepat\tis B vaccine.
30931/1
12/27 /85
00465
Study 859
STUDY PROCEDURE: Participants receive a 1 .0 ml intramuscular injection

of vaccine on Day 0, 1, and 6 months. Prior to
receipt of the vaccine, a serum sample is obtained
from participants to screen for HBsAg, antl-HBc, yeast
antibody and ALT levels. The vaccinees are asked to
record their temperature for five days after each
injection and note any local or systemic complaints.
If any unexpected or serious reaction occurs, they are
asked to notify the study physician innediately.
Follow-up blood samples will be obtained 1, 2, 3, 6,
8, 12, and 24 months after the first injection of
vaccine. The samples will be assayed for HBsAg,
anti-HBc, anti-HBs, ALT and yeast antibody. Sa~les
with an anti-HBs titer ~25 mIU/ml will be assayed for
anti-a and anti-d sub-type specificity. Assays for
ALT will be done by Or. Clumeck in Belgium. All other
assays on post-vaccination sera will be performed at
MSDRL in West Point.

10 mcg lot #978/C-K563 at 0, 1, and 6 months
Injection No.
_1_ __2_ _3_
31 31 0
2. Sero logic Results:

Sero logic data are avail ab le for 30 participants.
At three months, 80% (24/30) of the vaccinees
seroconverted for antl-HBs (S/N >2.1).
Fifty-three percent (16/30) of the subjects
~10) .
The GMT at three months for all vaccinees was 11.8

mIU/ml while it was 60.0 mIU/ml for responders
with a titer of mIU/ml ~10.
Refer to Table 1 for anti-HBs responses and GHTs
through three months of follo~-up.
30931/2
1/22/86
00466
Study 859
5
RES UL TS (CONT.): One subject (case (o) { ) was found to be anti-HBs
positive on the day ot the first injection. There
was no rise in antibody level after the first
injection and a >4-fold r1se in anti-HBs after the
second injection.
A summary of frequencies of clinical complaints

are not yet available. However. no serious or
alarming events attributable to vaccine have been
reported. Vaccination and follow-up continues in
progress.
30931/3
12/27 /85
Table l
ANTIBOOY RESPOtlSES FOLLOWING VACCIIIATION WITH RECOMBINANT HEPATITIS 8 VACCINE
STUOY 085'1
POFULATION HEALTH CARE PERSOtlNEl
DOSE 10 t1CG
LOT CK563
REGil1EN 0 , 1, AND 6 l10NTHS
I % WITH ANTI-HBS I GNT I NIU/NL l I

l---------------------------------------l-----------------------------------------------------1
I ~ I RESPOUOERS I
TINE l---------------------------------------l-----------------1-----------------------------------I
IMOHTHSI I SIN>: 2.1 I MIU/NL>: 10 I ALL VACCIHEES I SIN>: 2.1 I NIU/NL>= 10 I
···· ·································································•·¥••·········································
I
l MOIITH I 33% 110/30 I I 10¼ 13/30) I 1.1 I 9.2 I 31.4
I I I I I
2 MOUTHS I 63Y. (19/30) I 53% (16/30) I 8.2 I 38.3 I 58 . l
I I I I I
3 MONTHS I SOY. (24/301 I 53;1, C16/30 I I 11 . 8 I 27 . S I 60.0
I
·········································································································•~*••·····
0
0
~
0-
......
·-
0
l,C)
C0
>-
Q
.::,
1-
u,
001168
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepatit1 s 8 Vaccine,

Study 860.
PURPOSE: To evaluate ant1body and clinical responses to yeast

personnel who are negative for hepatitis B serologic
markers.

Lot ,f978/C-K563 (10 mcg HBsAg/ml)
PRINCIPAL Professor Dr. R. Laufs

INVESTIGATOR: Director, Institute for Medical Microbiology and
Innunology at the University of Hamburg
Martinistrasse 52
2000 Hamburg 20
WEST GERMANY
SECONDARY K. Katzner, M.D.

INVESTIGATORS: S. Gaterman, M.O.
Institute for Medical Microbiology and
Inmunology at the University of Hamburg
Martinistrasse 52
2000 Hamburg 20
WEST GERMANY
STUDY LOCATION: Institute for Medical Microbiology and

Inmunology at the University of Hamburg
Martinistrasse 52
2000 Hamburg 20
WEST GERMANY
DATE INITIATED: December 28, 1984
STUDY POPULATION: The study population consists of &O health care

who are negative for HBsAg, anti-HBc and anti-HBs,
have a nonnal ALT level and have not previously
30971/1
12/27/85
Study 860
PROCEDURE: Participants receive a l .0 ml Intramuscular injection

of vaccine on Day O, l, and 6 months. Prior to
receipt of the vaccine, a serum sample is obtained
from participants to screen for HBsAg, anti-HBc, and
anti-HBc, yeast antibody .and ALT levels. The vaccine
recipients are asked to record their temperature for 5
days after each injection and note any local or
systemic complaints. If any unexpected or serious
reaction occurs, they are asked to notify the study
physician immediately.
Fol low-up blood samples w11 l be obtained 1, 2, 3, 6,
8, 12, and 24 hours post the first injection of
vaccine. The saq,les w111 be assayed for HBsAg,
anti-HBc, anti-HBs, and ALT 1n Or. Laufs' laboratory
and may be assayed for yeast antibody at MSDRL. In
addition, an aliquot of serum from participants with
an anti-HBs titer >25 mIU/ml will be sent to MSDRL to
be assayed for antl-1.. and anti-g_ sub-type specificity
of ant1-HBs antibody.

10 mcg of Lot #978/C-t563 at 0, 1, and 6 months
l. Number vaccinated:
Injection No.
_1_ __2_ __3_
60 59 59
Serolog1c data are available for 56 participants
protective levels of anti-HBs (mlU/1111 ~10). The
GMT at 7/8 months was 2421.1 mlU/ml (all vaccinees
and responders by either cutoff).
Refer to Table l for GMTs and anti-HBs responses
30971/2
12/27/85
00470
Study 860
RESULTS (COti!T.): One subject was found to be seropositive for

anti-HBs on the day of her first injection. At
one month post the first injection of vaccine, she
had a >4-fold boost in anti-HBs titer.
47 parttcipants after each injection. The overall
frequencies of complaints are presented belO\il.

Complaint 1 2 _--=,3_ _
Injection 20(11/55) 28(15/54) 28(13/47)

Site
Systemic 20(11/55) 11(6/54) 11(5/47)

temperature data are provided 1n Table 3.
ALT Elevations
Four subjects had ALT elevations 1.5 to 3.5 times the
upper li~it of nonnal day O through 5 months, 3 months
after the second injection, one month after the second
injection, and four months after the second injection,
respectively. In all cases, the elevated ALT level(s)
have returned to nonnal. None of the subjects was
positive for HBsAg or anti-HBc.
. 6,(1\)
One subject (case I who had an elevated ALT level
1.5 times the uppe, jfflit of normal prior to the first
injection of vaccine, continued to have ALT elevations
at each subsequent bleed (1, 2, 3, 5 and 7 months post
the first injection). The ALT elevations range frOIII
2.0 to 3.5 times the upper limit · of normal. The
subject is HBsAg and anti-H8c negative. Further serum
samples and laboratory evaluation are pending.
3097I/3
12/27/85
Table l
AHTIBOO Y IIESPOHSES fOlLOMING VAtCIHATIOH WITH RECOt1BlNANT HEPATITIS B VACCINE

STUDY 0860
POrULATIOll HEAL TH CAIIE PERSOtnlEL
DOSE 10 MCG
LOT CK56l
REGIMEN 0, 1, ANO 6 MONTHS
I % MITH ANTI-HBS I GtlT I t1IU/11ll I

l---------------------------------------1-----------------------------------------------------I
I I I RESPOIIOEJ;IS I
TIME
I MONTHS I
l---------------------------------------l-----------------1-----------------------------------1
I 5/H >= 2.1 I t11U/Hl >: 10 I All VACCitlEES I SIN >= 2.1 I MIU/ML >= 10 I
**~••••••••••••••••••••••••••••••••••••••••••••••••-••••••••••••••~••••••••••••••••••••••••••••••••••v••••••••••••
I I
1 MOUTH I 431. (25/581 I 211. 112/581 I 1.3 I 8.6 I 19.4
I I I I I
2 t!OUTHS I 901. 152/581 I 831. 1481S81 I 60. 7 I 60 . 7 I 74.8
I I I I
3 MONTHS I 961. 154/S61 I 95% ISl/561 I l:!7.1 I 127.1 I 135.0
I I I I I
6 MONTHS I 1001. 1581581 I 981. (57/S81 I Zl7 . 0 I 217.0 I 229.7
I I I I I
7/6 1'10tlTHS I 1007. 1S6/561 I 1007. 156/5&1 I 2421.l I 2421. 1 I 2421.l
I I
·····················································-··········-··················································
0
0
..,
~
~
-
Table 2
STUDY 0860
TREATMENT
LOT 1-UIBER CK!56l
DOSE 10 HCG
PlTIEHT CLASS HEALTH CARE PERS0HNEL
• TOTAL VlCCINEES ( 60 PATIENTS) - DOSE 1 I

•----------------------------------------------------------------------------1
• DAYS POST VACCIW.,rlON • H\Jt181:R
CLINICAL
COHPUINTS
•----------------------------------------------------------------------------1
• 0 I 1 • 2 • l I 4 I 5 I
WITH
I COMPLAINTS
••••••••••••••••••••••••••-•••••••••••••••••• ••••••••••••••••••••••••••••••••• l•••••••••• l•••••••••• l•••••••••• I••••••••••
REACTIOlh LOCAL IIHJECT. SITE>
I
I 10 •
I l
I
• I 3
• o
I
I O
I• 0
II I
• 11
• , 1a.2;0 • , s.s;o I c s.sio I r o.oz, • , o.o:o • , o.o;o • • , 20.0?.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PAIN I 9 I l • 3 I o I o I o I I 10
I ( 16.41.1 I ( 5.5:iO I ( !5.5Y.I I ( 0.07.1 I ( O.OY.I I C o.o:o • • ( 111.27.1
I I I I I • I I
TENDERIIESS I l I o • o I o I O I o I I 1
I I l.8Y.I I C O.OY.I I ( O.OZ> I ( O.OY.I I I 0.01.1 I C O.OZI I I C 1.87.1
I I I I I I I I
SWELLING I 1 I o I o I o I o I o I I 1
I , 1.11Y.1 • , o.o:o I r o. oz, I r o . oY.1 I I o.o;o I c 0.01.1 I I c 1.e;:1
-----------------------------------1----------1----------l----------1----------l----------l----------l----------l-----------
svsrEMit I •3 I 4 I 5 I 4 I 3 I O I I 11
• < s.s:o • l 7 . JY.I I c •LtZI I 1 1.1;:1 I I s.sr.1 I c o.o;o I I 1 20.0;0
----------------------------------------------------------------------------------------------------------------------------
I
WHOLE IIOOY/GENERAL I ] 2 I 4 I 2 2 0 8
S.SY.I r 3.6l0 I c 7.:s;o I I 3,61.1 I 3.67.I ( o.o;o C l't . SY.)
FLUSH I 1 • I o I o 0 0 l
1. 8Y.) o.uo I C O.OZI I C 0.0?.I I D.OY.) ( O.DXI ( 1 . a;:1
Fl TIGUE/NEl KNESS I l o I 2
I
I 1 1 0 ,.
, o.o?.> I I c 1.e:o 1.8?.) O.OY.J 7 . Ji:I
HElOl CHE
I 1.8Y.)
1 z I
1 J.6:CI
2
I
• 2 2
' 0
' 5
1. BY.I ] . 6Y.I I C 3.67.1 I C ].6?.) 3.67. J O. DY.I I 9.17.)
' '
(
RESPIR ATORY 0 0 I 0 1 0 0 l
0 . OY.I o.a:o I 1 o.a:o 1.8?.I II. 117.l ( o.oz, ( 1 . 81.)
RHINITIS
' 0 0
I
I 0 1 0 0 1
0 . OY.) O.OY.I I I O.OY.I f 1.sr.1 O, DY. I ( 0.0% 1 ( l.BY.I
MUSCULOSICElETl l
' 0
' z
I
I 2 0 0 D 2
0. O?.I 3.6?.I I I 3 . 61.1 C O.OY.I O.OY.l ( o. o;o ( ] . 67.) 0
0
I:,
,, "'"
Table 2 (cont)
RECOt1BtNAHT HEPATITIS 8 VACCIHE
STUDY 0860
TREAT"ENT
LOT NIJHBER Cl<S63
DOSE 10 HCG
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES l 60 PATIENTS) - DOSE 1 I
1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUNBER
CLINICAL
Cot1PLAINTS
1----------------------------------------------------------------------------
I O I 1 I 2 I l I it I 5 I I MITH
I CONPUIHTS
•••••••••••••••••••••••••••••••••••!•••••••••• •••••••••• •••••••••• •••••••••• ••••••••••••••••••••••••••••••I••••••••••
I I
ARTHRALGIA IOTHERI I O 1 1 0 D O I 1
o.o;o 1 1.ex1 1 1.e:o , o.o:o , o.or.1 1 0.0:1.1 I 1 1.er.1
I
SHOULDER PAIN I O 1 1 0 0 O I 1
O.OiO I I.8i0 I 1.8:0 I o.o;o I o.o;o I 0.07.1 I I 1.er.1
I
DIGESTIVE SYSTEl1 I l O O 1 1 0 I 2
l.8i0 I 0.0XI I D.07.1 I 1.8:1.1 I l.8Y.I I 0.0Y.I I l l.6:1.1
I
NAUSEA I l O O O o o I 1
1.e;o l o.o:o I O.Ol() C 0.0iO I 0.0Y.I I o.o:o I l 1.8i0
I
GASTROENTERITIS, HOS I O O I O 1 I 1 0 I 1
0.0iO C o.o;o I C 0.0l(I C 1.87.1 I I l.8iO t o.0Y.I I I 1.er.1
I I I
UROGENITAL SYSTEH I 0 lI 0 0 I o 0 I l
o.o:o I I I 0.0Y.)
1.e:o C •• 0i'.1 I I 0.0Y.J t 0,07.1 I I 1.e,:1
I I I
OTHER I O 1 I O O I o O I l
I l 0.0:1.1 1 1.a:o I c o.o:o 1 0.0:1.1 I , o.o:o , o.o:o I 1 1.er.1
-----------------------------------1----------1----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH COHPLAINTS I 12 I 7 I 8 I ft I l I O I I 17
I , 21.er.1 I 1 12.1x1 I 1 1r,.s:o I c 7.Jr.1 I , s.s:o I I o.or.1 I I , lD.9:o
-----------------------------------1----------1----------l----------l----------l----------1----------I----------I-----------
PERSOHS WITH NO COMPLAINTS I 43 I 48 I 47 I 51 I S2 I 55 I I 38
I I 78.21.1 I ( 87.31.1 I ( 85.57.1 I ( 9~. 71.1 I t 94.5)0 I 1100.0Y.I I I I 69.lY.I
-----------------------------------1----------l----------1----------I------
PERSONS MITH NO DATA I 5 I 5 I S I 5
·---1----------1----------1----------I-----------
I 5 I 5 I I 5
I f 8.37.1 I I 8.3%1 I I 8.JY.I I I 8.JY.I I I 8.J;O I I 8.JXI I I I 8.3XI
0
0
.e
....
,
""
Table 2 (cont)

RECOt1BINANT HEPATITIS B VACCINE
STUOY 0860
Tl1EATl1ENT
LOT HUtl8ER Ck5U
DOSE 10 t1tli
PATIENT CLASS HEALTN CARE PERSONNEL
I TOTAL VACCINEES I 59 PATUNTSI - DOSE Z I

I1----------------------------------------------------------------------------a
DAYS POST VACCINATION I 1-M'eER
CLINICAL
COMPLUHTS
1----------------------------------------------------------------------------
I O I l I 2 I 3 I ti I S I
U WJTN
ICOt1PLAIHTS
•••••••••••••••••••••••••••••••••••l•••••••••• l••••••••••l•••••••••• l••••••••••l•••••••••• l•••••••••• l••••••••••I••••••••••
I I I I I I ,I I
RU CTION, LOCAL IINJECT. SITEI I 13 I 6 I 4 I 2 I l I l I I 15
I I 24.liO I I 11.liO I I 7 . 4Y.l I I 3.77.l I I 1.97.I I I l.97.1 I I I 27 . &i!I
-----------------------------------1---------- ---------- __________ ,__________ ---------- ---------- ----------0-----------
PAIN I 10 4 2 I l o o 12
IC 18.SiO I 7.47.1 I 3 . 7i0 C 1.97.1 I D.07.I C D.Di!I I 22 . 27.1
I
TENOERHESS I 1 O O 0 0 o l
I I 1.9"/.I I D.O::O C O.Oi!I C O. o:o I 0.D:O I 0.0:O I 1 .9i!I
I
SWELLING I 1 0 0 0 0 O l
I I 1.9i0 I o . o;o I 0.07.I I O. o:o I 0 . 0:O I 0 . 07.1 I 1 .97.I
I
P'llJ!ITIS I ITCHING I I 1 1 l O O O l
I I 1. 9i0 I l. 97.) I 1 . 9i! I I O. 07. I C 0 . o;o I O. o:o I 1. 97. I
I
ECCHYl10S I S I l 1 1 1 1 l l
I I l.9i0 I 1.97.) I 1.97.l I 1.97.) C l.97.I I I 1.97.1 I I 1.9% 1
-----------------------------------1
sysrEnic I
----------l----------l----------l----------l----------l----------l----------l-----------
3 I 3 I 3 I 5 I 3 I 3 I I 6
I I 5.6i0 I I 5.67.l I I S.67.1 I I 9.37.l I I 5.6l0 I c 5.6%1 I I I 11.17.1
I
WHOLE BOOY/GEHERAL I l 1 1 l 0 I 0 I I 2
l.9i0 C 1 . 97. ) I 1.97.1 C 1 . 97.) I •• 07.1 I I o.ox 1 I I I 3 . 7i! I
I
HU OACHE I l l 1 1 0 I 0 I I t
l . 9i(I C 1.9:o ( l.9Y.I I 1.97. 1 O.Oi!I I C 0.07.1 I I I 3. T/. 1
INFECTIOUS SYNDROMES I l l 1 2
' l I
I I
1 I
I
I 2
( 1.97.1 ( 1 . 9:0 C 1. 97.1 ( 3 . 77.1 C l.'IY.1 , , 1 . 97.1 I I I 3. 7Y.'
I I I
ItlFLUENZA, NOS I 1 1 1 2 1 I 1 I I t
1 . 97.1 C 1.9)0 ( l.9l0 C ]. 77.1 C 1.9%) I I 1 . <ix, I I I 3.7%1
RESPIRATORY I 1 l 1 2 2
I
I 2
.I
I
I
I 2
C l.97.I I 1 .9)0 ( 1. 91.1 ( :s.r.1.1 C J. 77.1 I C 3. 7i! I I I I :s.n, 0
0
I::
.....
J:,
...
Table 2 (cont)
PATIENT COUNT CLINICAL CottPUIHTS
REC01'8ItlANT HEPATITIS 8 VACCINE
STUDY 0860
TREATI1£NT
LOT NltlBER CK56 J
DOSE 10 1'1CG
I TOTA L VACCINE ES C 59 PATIENTS I - DOSE t I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUtfflER
CLINICAL
COttPLAINTS
l----------------------------------------------------------------------------1
I O I l I 2 I J I 4 I 5 I
WITH
I COMPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
I I I I I I I I
RHINITIS I 1 I l I l I t I 2 I 2 I I 2
I l 1. 9Z I I l 1. 9i0 I t 1. 97. I I c l. 7,0 I c 3. 77. l I I 3. 7l0 I I < 3. 7?. I
I I I I I I I I
PH ARYNGITIS I SORE TlfROAT> I a I a I l I 1 I 1 I 1 I I l
I C 0.0'l.J I l O. OY.I I I 1.97.) I C 1.97.) I I 1.97.) I I 1.97.) I I l 1.9Y.I
-----------------------------------1----------1----------l----------l----------1----------I----------I
PERSONS WITH totlPU INTS I 16 I 9 I 7 I 7 I 4 I 4 I----------I-----------
I 20
I l 29 . 67.1 I I U..77. ) I I n.o;o I C l l . 117.1 I I 7.47.) I I 7.4)0 I I I 37 . 0lO
-----------------------------------1----------l----------l----------l----------l----------l----------
PERSOHS WITH NO t0f1PUINTS I 38 I 45 I 47 I 47 I 50 I SO
t----------t-----------
I I 34
I I 70 . 4Y.I I ( 8J.lY.) I ( 87.07.1 I C 87.0'l.l I I 9Z.6'l.l I I 92.6'l.) I I 1 6'J.Or.)
-----------------------------------1----------1----------1----------
PERSONS WITH tlO DATA I 5 I S I 5
I----------I----------I----------I----------
I 5 I 5 I 5 I
I-----------
I 5
I t &.sz1 I , a.s✓. , I , a.s:o I c a.s:o I , a.s:o I , a.sr.1 I I , a.sr.1
...,,,.
0
tJl
•
Table 2 (cont)
PATIENT Cou-lT CLINICAL COHPLAIHTS
RECot18INAHT HEPATITIS 8 VACCINE
STUDY OMO
TRUTM£HT
LOT HUNBER CK56l
DOSE 10 HCG
PATIENT CLASS HEALTH CARE PERSONHEL
I TOTAL VACCIHEES C 59 ,PATIEHT51 - DOSE 3 I

1--------------------------------·······-···--·········-······-······-·······1
I DAYS POST VACCIHATIOH I IM1BER
ClIHICAL 1·····-·················-·······-····•·-·•····--··-····--·-•···············•-1 MITH
COHPLAIHTS I D I 1 I 2 I J I 4 I S I ICOHPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I . I I I I I I I
REACTION, LOCAL UHJECT. SITU I 9 I II I l I 2 I 1 I o I I 13
I c 19.67.1 I I 17.07.1 I c 6.47.1 I I 4.31.1 I c t.17.1 I c 0.07.t I I c 27.77.1
·············-·········-·······---·I·········· ······-···1·········· ·-····-··· ·-·--·-·-- ····-····-1-··-·-··••I·•-····-·-·
PAIN I 11 4 I 2 l O O I I 9
17.47.) I 8.57.1 I C 4.37.1 I 2.17.1 ( 0.07.1 I o.o;o I I I 19.17.I
I I I
SORENESS I 0 l I O O 0 D I I l
O.OY.I I 2.llO I C 0.117.) I O.OiO I t.0%1 I 0.0%1 I I I 2.lY.l
I I I
PRURITI9 IITCHINGI I 1 2 I 1 l 1 0 I I 4
2.27.1 I 4.3%1 I I 2.17.1 I 2.11.1 f 2.1%1 I o.o::o I I I a.s::o
I I
HE11ATOHA I O l I O o I O I I l
I I 0.07.) I 2.lXJ I I o.o:o I o.o;o I 0.07.1 I 0.0%1 I I I 2.1::0
···-····-········-···-·--···--·----1-··---··-·1·--·---·-·1·---·-·--·1-·--·--···1··--------l---·------1·----·---·1-···-····-·
SYSTEHIC I 2 I 1 I 2 I 2 I 3 I 1 I I S
I c 4.37.1 I I 2.1,0 I c 4.JlO I I 4.37.J I c 6.47.t I c 2.lY.t I I c 10.67.J
._.DLE BODY/GEHERAl I
(
0
o.o::o ( •
o.o:o I
1
2.1:0 (
0
o.o:o I
D I
O.OY.J I I
0
u.a;o I
I I
I t
l
2.17.1
I I I
HEADACHE 0 0 l 0 0 I II I I 1
I 0. 07. J I o.o::o C 2 .17.1 I 0.01.) I O.OY.I I I O.OY. I I I t 2.1:t.l
INFECTIOUS SYNDRONES 0 0 0 0 l I a I I 1
( 0.0:1.) ( O.OY.l I O.OY.) I o.a;o t 2.lY.1 I I o.ox1 I I c 2, l:1.1
I I I
IHFLUEIIZA, NOS 0 0 D D 1 I 0 I I 1
I 0.0:t.J I o.o:o 1.0;0 0.0:t.J 2.17.l I I 0.07.l I I t 2, 17.1
' '
(
I I I
RESPIRATORY 1 l l 1 1 I 1 I I 1
I 2 .27.1 I 2.17.) ( 2 .17.1 2 .17.1 I 2.11.1 I 1 2.11.1 I I t 2.1?. I
RHINITIS 1 l l
' l 1
I
I 1
I
I
I
I l
2.2:0 2.1::0 ( 2.1:0 ( 2.1x1 I 2.11.1 I t 2.1:0 I I c 2.1?.)
' 0
0
,::,
.....
0-
Table 2 (cont)
PATIENT COlMT CLINICAL COHPLAINTS
RECot18IHAHT HEPATITIS 8 VACCIHE
STUDY D86D
TRUTt1EHl
LOT tU1BER Ck5bl
DOSE 10 t1CG
PATIENT CLASS HE ALTH CARE PERSOtl-lE L
---~------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES C 59 PATIENTS I - DOSE 3 I
1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUttBER
CLI NICAL
COffl'LAINTS
1-----------------------·-·---------------------------------------··---------I
I O I l I 2 • 3 I 4 I 5 •
MITH
IC011PLAINTS
••••••••••••••••••••••••..••••••••••••••••••••!•••••••••• •••••••••••••••••••••••••••••••• ••••••••••••••••••••I••••••••••
I I • I •
DIGESTIVE SYSTEt1 I l I O O • 1 1 I D I 2
I ( 2.2Y.I I ( O.OY.I I D. 01.l • I 2.lY.I l 2.lY.1 • I O.DY.I I I 4.3i0
I I I I
DIARRHE A I l I O O • 0 0 D I l
I ( 2 . 2i0 I ( O.Oll l D.01.l • C 0 . 021 ( 0.0%1 I D. o:o I I 2 . 17.1
I I I I
NAUSE A I l I o o I O o o I 1
I l 2.27.1 I l O.Oll < O.OiO I l O.Di'!J I 0.07.1 I o.o:o I l 2.1:0
I I I I
GASTROENlEAITI9, NOS I O I O O I 1 l o I l
I ( 0.0%1 I I D.OY.I f o.o:o I l 2.17.1 l 2.liO I O.OY. I I I t.lY. I
I I I I
ORGANS OF SPECIAL SENSE I 1 I 1 1 I 1 1 l • 1
I 1 2.2x1 I l 2.1z1 1 2.un I t 2 . 1i1 1 2.uo c 2 . 1;. 1 • t 2.1:1.1
I I I I
CONJI.JICTIVITIS I 1 I 1 1 • 1 l l • 1
I l 2.2;0 I I 2. 17.1 C 2.11.1 I I 2.lY.I I I 2.1,:1 C 2.lY.1 • I 2.liO
-----------------------------------l----------l----------1----------1----------1----------
PERSOtlS WITH COl1PLAINTS I 11 I 9 • 5 I 4 • 4
----------1----------1-----------
1 • • 17
I I 23.9%1 I ( 19.17.1 I f 10.6:1.l • C II.SY.I • l 11.s;o I I 2.lY.l I I I 36.2XI
-----------------------------------1----------l----------l----------l----------•----------I----------I---------- I-----------
PERsONS MITH NO COMPLAINTS I JS I 311 I 112 • 43 I 43 . I 46 I I 30
I f 76 . 1%) I l 80.9:0 I I 89.47.l I I 91.SY.) I I 91.SXI I I 97.9X, I I I 63.8:1.I
--------------------. --------------l----------l----------1----------1----------1----------I----------I----------I-----------
PERSONS WITH NO DATA I 1 I 1 I 1 I l I 1 I 1 I I 1
I I 2.lY.1 I I 2 . 17.l I I 2.lY.I I I z.1::0 I I 2 . lY.t I I 2.uo I I I 2.uo
0
0
........
C
-
Table 3
PATIENT C ~ HlXlfflJl1 lEl1PERll\lR(S
RECOt1BINANT HEPATITIS B VACCINE
STUOY 01160
TREAT11EHT
LOT Hl.lf18ER CKS63
DOSE 10 11CG
PATIENT CU SS: HEALTH CARE PERSONNEL

l---------------------------------------------------------------------------------------1
11AX TEHPERl TtmE
I DEG f • Ol!ALI
l---------------------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I 5 I I .
WITH
I HAX TEl1P
•••••••••••••••••••-•••!••••••--•• •••••••••• •••••••••• •••••••••• •••••••••• ••••••••••l••••••••••l••••••••••I••••••••••
I I I
< ,9 I 15 30 29 25 26 24 I I 12
I ( 37.Sl!I I 54 . SY.I ( 52.7%1 I lt6.3Y.I I 47.]iO I 45.3)0 I I I 21.a:o
I I I
9'1 - 99. 9 I 23 22 25 27 'l7 27 I I 35
I ( 57.SY.I I 40.0)0 I 45.s:o I so.o:o I 49.llO I 50.9XI f · I I 6].6Y.I
I I
100 - 100.9 I 1 2 1 2 2 2 I I 6
I I 2.SZI I 3.6Y.I I 1.8:0 I 3. Tl.I I 3.6i0 I 3.8ZI I I I U.'IZI
I I
101 - 101. 'I I 1 1 o D o o I I 2
t , 2. s;o 1 1. 8Y. 1 1 o. ox I I I o. oz, I c o. or. 1 , o. oz I t I , J. 6?.1
------------------------t----------t----------l----------l----------1----------
TEHPERlTURE TAl< EN I 40 I 55 I 55 I 54 I 55
l----------
I 53
1---------------------1I -----------
I SS
I C 66 , Tl. I I C 91. 71. I I C 91. Tl. J I I ,o. oz J I I 91. 7Z I I f 88. 3i! I I I I 91. 7Y. I
------------------------l----------
TEHPER ATURE NOT TAKEN I 20
l----------t----------l----------
I 5 I 5 I 6
l----------1----------1---------------------
I S I 7 I
t-----------
I 5
I I 33.3%1 I I 11.:s:o I I 8.3Y.I I I 10 . or.1 f I 8.3)() I I ll.7i!I I I I 8 . ])()
0
0
.e:
....,
.. 0t
Table 3 (cont)
PATIENT COUNT HAXINUtt TEHPERAT~ES
RECOMBINANT HEPATITIS B VACCitlE
STUDY 0860
TREATMENT
LOT NUt1BER Cl<S6l
DOSE 10 ttCG
PATIENT CLASS HEALTH CARE PER~E L
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES C 59 PATIENTSI - DOSE 2 I
1• ---------------------------------------------------------------------------------------
DAYS POST VACCINATION t
I NUHBER
" AX TEHP(RATURE
1DEG F , m•u
l---------------------------------------------------------------------------------------1
• o I 1 I 2 I J I 4 I 5 I I I nAxMITH
TEHP
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••• l•••••••••• l••••••••••l••••••••••l••••••••••I••••••••••
• I I I I I I I
< 99 • 11 I 26 I 29 I 25 I n I 21 I I 1s
I C 39,5;1,1 I C 411.17.l I I SJ.Tl.I • I 47.2:I. I I I so.o:o I I S5 . lZI I I C 21.8?. I
I I I • I I I I
n - 9'1. 9 • 25 I 24 I 22 I 27 I 26 I 21 I I 33
f I 58.11.1 I f lt4.47.I I I 40. Tl.I I f S0.9:1.I I I 48. } l(J I I 42.9)0 I I f 61.17. 1
I I I I I I I I
100 - 100. 9 I l I 4 I 3 I l I 1 I 1 I I 6
I C 2. 31. I I ( 7. 4Z l I I S. 6i0 I I l. 9i0 I I 1 . 97. I I l 2. OJ! I I I I 1 1. 17. 1
------------------------•----------1----------l----------l----------1----------1----------1---------------------I
TEHPERATWE TAl<EH I 43 I 54 I S4 I SJ • 54 I 49 I I
-----------
54
I 1 12.91.1 I , 91.5l!I I 1 91.sio I c 89.&io I c 91.5:0 I , 83.uo I I , 91.sY.1
------------------------l----------t----------l----------1----------1----------1
TENPERATURE HOT TAl<EN I 16 I 5 I 5 I 6 I 5 I
----------t---------------------l-----------
10 I I S
I I 21.11.1 I I 8.5:I.I I f e.s:o I I 10 . 2:1.1 I C &.s:o I C l6.9Y.I I I C 8.5)0
0
0
...,
~
..t,
--
----
Table 3 (cont)
PATIENT COUNT ttAXIt1Ut'I TEHPERATURES
RECOl18IHAHT HEPATITIS B VACCINE
STUDY 0860
TREATl1ENT
LOT tU!eER Ck563
DOSE 10 l1CG
PATIENT CLASS HE ALTH CARE P£RSONNfl
• TOTAL VACClHEES I 59 PATIEHTSl - DOSE 3 I

•---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I IU19ER
11AX TENPERATURE
IOEc;F,ORALI
1•--------------------------------------------------------------------------------------1
IO I 1 I 2 I 3 I 4 Is I I
MITH
IHAXTEttP
•••••••••••••••••••••••••••••••-••I••••••••••••••••••••••••••••••••••••••••••••••••••
I
••••••••••l•••••--•••I••••••••••
< 99 I 15 I 14 19 22 23 24 I u
37 .s:o I 1 11.1::1. 1 1 1t1. 2::1. > 1 lt7 .8::t.> 1 s1.1:1. 1 1 S4.s:o I , n. 9;0
I I
99 - 99.9 I 2t I 28 n n 18 18 8 21
55.0¼J I I 62.2¼1 I 52.l¼J I lt5.7i0 I 40.0:1.1 I 40.91.1 I I 58.7¼1
I I
100 - 100.9 I J I 2 2 3 l 2 I 6
7.5¼) f I 4.4?.I I 4.5:o I 6.57.1 ( 6.71.1 I 4.Si!) I I U.O¼I
I I
102 - 102. 9 I o I 1 o o 1 a I 2
I I 0.0?.I I I 2.2?.I I I 0.0iO I I o.az, I 2 . 21., I o.a:o I I 4.3¼1
------------------------l----------l----------l----------l----------l----------1----------1---------------------•-----------
TEHPERATLRE TAKEN I 40 I 45 I 44 I 46 I 45 I 44 I I 46
I t 67.8,o I t 76.3¼> I 1 74.6Xl I 1 1a.o:1.1 • , 76.liO I , 74.6:1.1 I I 1 ,e.a;o
------------------------l----------1----------l----------1----------1----------1
TEHPERATURE NOT TAKEN I 19 I 14 I 15 I 13 I 14 I
----------1---------------------
lS I
I-----------
I 13
• I 32.2l!I I I 23.7¼1 I I 2.5.4i0 I I 22.0i!I I I 23 . 7Y.I I I 25.4?.I I I t 22.0;0
0
<:>
.t,
OIi
0
·-
STUDY 869
001l8l

Study 869
PURPOSE: To evaluate ifflllunological and clinical responses to

yeast recombinant hepatitis B vaccine in health care
personnel who are negative for hepatitis 8 virus
serologic markers.

Lot #81991D/18068/C-L217
PRIMARY James G. Rankin, MB, BS, FRACP, FRCP(C)

INVESTIGATORS: D1rector, Canadian Liver Foundation
Epidemiology Unit and Professor
Faculty of Medicine
University of Toronto
12 Queen's Park Crescent west
Toronto, Ontario M5S 1A8, Canada
Randall A. Coates, MO, HHSc
Assistant Professor
Canadian Liver Foundation
Epidemiology Unit
12 Queen's Park Crescent West
SECONDARY David Stewart, MD, DECH, CCFP

INVESTIGATORS: Medical Director, Department of
Occupational Health and Safety
2015 Bayview Avenue
Sunnybrook Medical Centre
Toronto, Ontario M4N 3M5, Canada
Mabel L. Halliday, MO, DPH, MSc
Assistant Professor
Canadian Liver Foundation
Epidemiology Unit
12 Queen's Park Crescent West
STUDY LOCATION: sunnybrook Medical Centre

2015 Bayview Avenue
Toronto, Ontario M4N 3MS, Canada
21111/801/1
1/2/86
00482
Study 869
DATE INITIATED: May 1985
STUDY POPULATION: The study population will consist of health care

are negative for hepatitis B virus serologic markers,
have a nonnal ALT level and have not previously ·
PROCEDURE: The study w111 be conducted in two stages. Stage I

will include 30 participants and Stage II 120
participants. Participants will receive a 0.5 ml
(lO~g HBsAg) intramuscular injection of vaccine at
O, l and f> months. Study subjects wi 11 be asked to
record their temperatures and any local or systemic
complaints for five days after each injection.
Blood samples will be obtained prior to vaccination,
on Day 0, and at l, 2, 3, 6, a. 12 and 24 months post
the initial injection. The pre and two-month sample
will be tested for ALT. All samples will be assayed
for HBsAg, anti-HBs and anti-H8c. Pre-vaccination
tests will be perfonned in Toronto and post
vaccination tests w111 be completed by MSORL. Assays
may also be done for yeast antibodies and anti-HBs
subtype specificity.

10 mcg lot #81991D/1B068/C-L217 at 0, 1, and 6 months
Dose Injection No.

Level _1_ __2_ __3_
10 mcg 71 71 0
2111 I/801/2
l /2/86
ooa83
Study 869
RESULTS: (Cont.) 2. Serologic Response:

who received two injections of vaccine. At one
month, 32% (22/68) of the participants
seroconverted for anti-HBs S/N > 2.1. Twelve
percent (8/&8) developed protective levels of
anti~HBs (mIU/ml ~ 10).
The GMT at one month for al 1 vaccinees was 1.2
mIU/ml and 44.8 mIU/ml for responders with a
titer of mIU/ml ~10.
Serologic follow-up continues in progress.
participants after injections one and two. The
below:
Type of Freauencv in% bv Injection No.

Complaint l 2
Injection site 24 (17/71) 10 (7/71)
Systemic 30 (21/71) 17 ( 12/71)

2111 I/B0I/3
1 /2/8£,
00484
Study 869

One subject, a 46 year-old female health care
worker, reported the onset of generalized
prur1t1s 9 hours after administration of
vaccine. Prur1tis continued during the following
24 hours accompanied by 1rritab1l 1ty , nausea and
parasthesias under the left breast. These
symptoms resolved on the second and third days
post vaccination. However, the participant
reported that her extremities felt stiff and
heavy. Her past medical history is significant
for parasthesias which occurred l year prior to
vaccination when a mass was surg1cally removed
from her left breast. The investigator felt the
subjects reaction had an emotional component and
was probably not related to administration of
vaccine.
21111/801/4
1/2/86
Table 1
PATIENT COIJHT CLINICAL Cot1PlAIHTS
REC011BIHAHT HEPATITIS B VACCINE
STUIJY 0869
TIIUTl1ENT
LOT NUtl!ER CL217
DOSE 10 t1CG
PATIEITT CLASS HEALTK CARE PERSOHNEL
I TOTAL VACCINEES ( 71 PATIENTS! - OOSE l I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUl'IBER
CLINICAL
COl1PLAIITTS
1----------------------------------------------------------------------------I
I O I l I 2 I l I 4 I S I
MITH
ICOHPLAIHTS
·································••l••······••l••······••l••······••l••······••l••······••l••······••l••······••I••········
I I I I I I I I
REACTION, LOCAL !INJECT. SITE! I 14 I 7 I 'J I l I l I 1 I I 17
I I 19.T/.I I I 9.9%1 I I 4.21.1 I I 1.4%1 I t 1.4%1 I I 1.4%1 I I I 23.9%1
-----------------------------------1----------I----------
IHFLAt1t1ATIDN I l I O
----------
O
----------
O
----------
o ----------
o ---------- -----------
1
I I l.4i0 ) ( 0.0%1 I o.o:o I 0 . 0%) I o.o:o I o.o:o ( 1.4%)
I
PAIN I l l O O O O 2
I ( 1.4%1 I l.4i0 ( 0.01.1 ( O.o:;o I 0,0%1 I 0.0%1 I 2.8%1
I
SORENESS I 9 J 2 l l 1 10
I I 12.T/.I I 4.2%1 I 2.81.1 I 1.4%1 < 1.4%1 I l.4l0 I 1".lY.I
I
TENDERNESS I 2 2 1 0 0 0 4
I 1 2.8:o 1 2.aY.1 1 1.41.1 1 0.01.1 1 0.0%1 c 0.0%1 1 s.6%>
I I
Pl!UIIITIS I ITCHING I I l 1 I o O D D 2
I f 1.4i0 I 1.4)0 I I 0.01.1 I D.0%1 t 0.0%1 I I 0.0%1 I t.8%1
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
sYsTE111c I 12 I 6 I 7 I 6 I 7 I 2 I I 21
I I U..9i0 I I a.SY.I I c 9.91.l I c 8.5%1 I 1 9.9%1 I I 2.ex1 I I I t9.6i0
I
WHOLE BOOT/GENERAL I 7 0 I 2 l 1 I 0 I I 10
9 . 9%1 ( 0.0%1 I I 2.8%1 ( l.4%1 I 1.4%1 I 1 o. ox1 I I I 14.1%1
I
FEVER !TEMP. NOT REPORTED> I 0 0 I l 0 0 I 0 I I l
o.o:o I 0.0%1 I I 1.4%) ( 0.0%1 I 0.0;:1 I I 0. Oi:I I I r 1.4%)
I I
CHilLS I 1 0 I 0 0 0 I 0 I I l
1.4%) ( 0.01.1 I 1 o.o:o I 0.0%1 ( o .ox, I 1 a.0%1 I I I 1.4i:I
I I I I
SWUTitlG I 2 0 I 0 0 0 I 0 I I 2
2.8%1 ( 0.0%1 I I 0.0%1 I O.OlO ( 0.0%1 I I O.CJY.I I I < 2.8%1
I I I I
SENSATION OF WARNTH, GENERAL I 1 0 I 0 0 0 I 0 I I l
1.4%1 ( 0.01.1 I f 0.0%1 f 0.0%1 f O.CJlO I ( o. 0% I I I I 1 . 41.1 0
0
~
CD
VI
.,
Table l (cont)
PATIEHT COUHT CLINICAL COt1PlAJHTS

RECOHBIHAHT HEPATITIS B VACCJHE
STUOl 0869
TREATNEHT
LOT IIIJl1BER Cl217
DOS[ 10 tlCG
PATIENT CLASS HEALTif CARE PERSONNEL
-- - ---
--------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES I 71 PATIENTS)• DOSE l I
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I MJl18ER
CLINICAL
l----------------------------------------------------------------------------1
, ,
WITH
COHPUINTS I 0 I 1 I l! I 3 I 4 I 5
................................... .......... ...................................•.... .................... •......•..
I I
I ICDNPLAINTS
,
I
,I
FA TIGUE/MEAl<tlESS I 0 I 0 1 0 0 I 0 I l
I c o.o;o ( 0, Oi'.I ( l.4ZI ( O.Oi'. I I o.aio I c o.o:o I I 1.4:1.1
I I I
HALAISE I l
I I l.4ZI I
0
O.Oi'.)
0 0 0 I
I • I
I
1
HEADACHE
I
I 2 0
I O.OZI
l
' 0.0%1
l
I 0.DY.I
l
I
I
I 0.0%1
D
I
I
I 1.4:I.I
5
I c 2.8:1.) I O.O'iO ( l.4Zl I 1.41.1 I 1.410 I I 0.,:1.1 I 7.0l!I
I
LIGHTIIEADED I 2
2.8%) (
0
o.ax, (
a
D. OlO I
0
0 . 01.1 (
0
O.OY.I ( •
O.tY.I (
2
2.8%1
ACHINESS I 0
0.0)0 (
0
O.Ot I I
0
o.o;o (
l
1.4:1.1 I
0
o.o:o ( •
0.0:1., I
1
1.4%)
HOT ANO COLO FLASHES I

I I
1
1,4:1.J (
0
O. Ot) I
0
o.o:o I
0
o.o:,o (
0
O.OY.I ( •
o.o:o I
l
1.4:1.1
I
RESPIRATORY I 2 2 2 3 4 l s
2.8%) ( 2.81.) I 2.8:1.l I 4.2l!I ( 5.6%) ( l.4l!I ( 7.0%1
II '
RHINITIS I 0 l 0 0 l 0 2
I I o.o:o ( 1.4::0 I O.Ol!I (
'
( O.Ol!I l .4'iel O.Ol!l I 2.8l!I
I
PHARYNGITIS I SORE THROATI I 2 l 2 3 4 l 5
2,8)0 ( 4 . 1!)0
I I
' l.ltiO
1.41.) l!.8% ) I 5.6i0 C 7.0r.l
I
11USCU LOSKHETAL I 2 2 2 l 1 0 s
2.8)0 ( 2. 8 7.) ( 2.8%1 I 1.4%1 ( l.lt%1 ( o.o,o ( 7.0%)
I I
ARTHRALGIA IOTHERI I l 0 0 0 I 0 0 1
I c 1,4;',I I o.o:o I 0.0lO I O.Ol!I I I O.Ol!) I 0 . 0%1 ( 1.4%1
I I
SHOULDER PAIN I 0 0 l 0 I 1 0 2
o.o:o I o.o;o ( l. 4?.) I 0. Ol!I I I 1.4?.I I 0.0%1 I 2 . 8%)
I 0
NECK STIFFHESS I 0 2 1 1 I 0 0 2 0
O.OY.I ( 2.8?.l ( 1.4%1 ( 1.4?.I I I 0. 0?.I r o.o:o I 2.8Zl ~
CJI
C7'
!II
Table 1 (cont)
PATIENT COIJHT CLINICAL COHPLAINTS

RECOt18INAHT HEPATITIS B VACCIIIE
STUO'i' 01169
TREATtlEHT
lOT NUIIBER tl217
DOSE 10 MCG
PATIENT CLASS HEALTH CARE PfRSOHNEL
I TOTAL VACCINEES I 71 PATIENTSJ - DOSE l I

1·--------------------------·------------------------------------------------1
I DAYS POST VACCINATION I NUtfflER
CLINICAL
Cot1PLAIHTS
1---------------------------------------------------------------------------·1
I 0 I l I 2 I 3 I 4 I 5 I
MITH
I COMPLAINTS
••••••••••••••••••••••••••••••••••• ••••••••••I•••••••••••••••••••• ••••••••••l••••••••••l••••••••••l•••••••••al••••••••••
I I
ARN PAIH l 0 0 0 I l 0 l
1.4:t.J ( o.o:o ( o.o;o ( o.o;o I, 1,4:t.J ( o.o:o ( l.4:t.l
OTHER l
1.4)0 ( •
0.0:1., I
0
0.07.1 I
0
0.0%) I
0
0.0%) I
0
0.0%1 (
1
1.4:t.)
DIGESTIVE SYSTEH J l l l l 0 5
4.2?.I I 1.41.1 I l.'t:t.l ( 1.4:t.) ( 1,4:t.l I O.OiO C 7.0:t.l
DIARRHEA 0 0 I l 0 0 l
,.0:1.1 ( 0,0ZI I l.4%1 I l.4i0 C 0.01.J C o.ox, C 1.4%1
NAUSEA ] I l 0 0 0 4
4 .2%) I 1.4i0 I l ,It% I I o.ox, ( O,OXJ C O.OXI ( 5.6XI
VOt1ITIIIG 0 0 l 0 l 0 2
,.ox, ( 0.0%1 I l.4i0 I o.ox, ( 1,4X) I o.ox, I z.ax,
NERVOUS SY9TEH 1 1 1 1 1 l 3
1.'t:t.l ( 1.4)0 I 1.4%) ( l.4i0 ( l.4i0 I 1.4?.I I 4.2:t.l
PARES THE SUS 0 0 1 l l 1 l

o.ox, I o.o;o ( 1.4%1 I 1.4:t.l ( l.4XJ C 1.4%1 I 1.4Y.I
TMITCH/LOCAL SPASHS I 1 I l I D I 0 I 0 I 0 I I Z
I I 1.4:t.) I ( l.41.1 I ( 0.01.1 I t 0.0%) I ( 0.0%) I ( 1.0%1 I I I t.6%)
------------------·----------------1----------1----------1-----·----l------····1----------1-··--·----I----------I-----------
PERsOHs WITH cot1PLAINTS I 23 I 12 I , I 7 I a I :, I I 12
I I 32.4%1 I I l6.9i0 I I lt. 710 I I 9,9XI I I Il.3i0 I I 4.2iO I I I 45.lXI
-----------------------------------1----------l----------l----------l----·-----I----------I----------I----------I-----------
PERSONS WITH NO COttPU.tHTS I 4& I S<J I 62 I 64 I U I 68 I I 39
I 1 67.6%> I , 113.1,n I , &7.3%1 I , 90.1x1 I , ee.7Y.J I , n.ax, I I 1 54.9:t.J
-----------------------------------l----------1----------1----------1----------l----------l----------l----------l------·----
PERSONS MITH HO DATA I o I O I O I O I O I o I I o
I I O.OXI I I O,OZI I I 0.0%1 I I 0.0?.I I I O,D?.J I I O.OY.I I I I O.OZJ
0
0
~
OD
....,
-
Table 1 (cont)
PATifNT COUNT CLINICAL Cot1PLAIHTS

RECOtlBINANT HEPATITIS B VACCINE
STU>Y 0669
TREATMEHT
LOT tM1BER CL217
DOSE 10 11CG
PATIENT CLASS HEALTH CARE PERSOttlEL

Il----------------------------------------------------------------------------1
DAYS POST VACCINATION I HUttBER
CLlHIC Al
COMPUIHTS
1----------------------------------------------------------------------------
I O I l I 2 I 3 I 4 I S I
Il cot1PLAINTS
WITH
•••••••••••••••••••••••••••••••••••l•••••••••• l•••••••••• l•••••••••• l•••••••••• l••..••••••••••••••••• l••••••••••I••••••••••
I I I I I I I I
REACTION, LOCAL I INJECT. SITE I I 7 I 3 I 1 I o I O I D I I 7
I I 9.9l) I I 4.2%1 I I 1.4%1 I I 0 . 0%1 I I 0.07.) I I O.D%) f I ( ,.,x,
-----------------------------------1----------1----------1----------
SOREHESS I 3 I 2 I o ----------1----------
O I o ----------1----------1-----------
o I I J
4.2:!I I I2.11:0 I I O. OiO ( 0.0%) I ( D.07.) I 0.0)0 I I ( 4.2%1
I I I I I
TENDERNESS I 2 I 1 I l O I O D I I 2
2.11:r.1 I 1 1 .47.1 I 1 1.47.I c 0.0:r.1 I t o.o;o , o.ox, I I , 2.ex1
I I I I I
STIFFHESS/TJGHlNESS I l I o I O O I o o I I l
l.47.I I , o.o:o I t o.o:o , 0.0:r.1 I I o. o;o < o.oY.1 I I 1 1.t+z1
I I I I I
PRURITIS t ITCHING I I l I o I 0 0 I 0 0 I I l
1. 1 1.4½) I , o.oz1 I t o.o:o , o.o:o I < o.o;o , o.o:o I I c 1.4:t.1
-----------------------------------l----------l----------l----------l----------
svsn111c I 7 I 6 I S I 3
l----------l----------l----------1
I 4 I 3 I I
-----------
H
I 1 9.97.I I < 11.s:r., I 1 7. o:o I , 4.2:0 I c s.6¼1 I , 4 . zx, I I , H.9Y.J
I
MHOLE BOOY/GEHERAL t 5 I 3 3 I 0 I 0 I 0 I I 9
1.0:r., I 1 "· 2%, ( 4.2:0 I f o.o:o I f o.ox, I < 0.0:r.1 I I I 12.n1
I I I I I I
f AlIGUE/WEAl<HESS I 2 I 0 0 I 0 I 0 I 0 I I 2
2.sx, I < 0.0%) I o.o:o I I 0.0:r.1 I , o.o:o I 1 o.o:o I 2.8:t.l
I '
NALAISE I 1 I ,. ,. I
I 0 I 0 I 0 I I 2
I I 1.4%1 1.4:o I c o.oio I c o.ox, I 1 o.,:o I 2.8?.I
HEADACHE I
l .4l0
J
I
I 2
' l
I
I 0
I
I 0
I
I •
I
I
II '
I s
( 4.2)0 I I 2 . 8?.) ( l.ttXI I ( 0.0?. I I I o.o:o I , o.e:o I I I 7.0)0
I I I I I I
LIGHTHEADED I
I
l I
l.4%1 I 1
0
0.07.J (
0 I
o. ox, I
0
, o.ox1 I
I 0 I -
f o. o:o I 1
• I
o. , x, I
I
I I
1
l. 4Y.I
I I I I I I
HOT FLASHES I 0 I 0 1 I 0 I 0 I 0 I I 1
o.ox1 I 1 o . o:o ( l.47.) I I o.ox1 I • o. OY.) I I a.ex, I II 1. 4?.J 0
0
""a,
a,
.,,
Table l (cont)
PATIENT COUNT CLINICAL CottPLAIHTS
AECOl18ltlANT HEPATITIS B VACCIIIE
STU>Y 0869
TREATMENT
LOT Hllt18EA CL217
DOSE 10 11C&
-- -------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES C 71 PATIENTS! - DOSf. 2 I
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUl18EA
CLINICAL l----------------------------------------------------------------------------1 MITH
CONPUIHTS I D I l I 2 I 3 I 4 I 5 I ICDNPLAIHTS
••••••••••••••••••••••••••••••••••• •••••••••• ••••••••••1••••••••••1•••••••••• ••••••••••l••••••••••l••••••••••I••••••••••
I I
RESPIRATORY D 1 I 1 D 1 I 1 2
o.o:o ( I
1.47.1 C 1.4Y.I ( o.o:o ( 1.4;0 I 1 1.4%) ( 2.6%)
I I
RHINJTI5 0
o.o;o (
l
l.4XI I
I
I
1
l.4Y.I (
0
0.07.1 (
0
0.0%)
I ., 0
0.0)0 (
l
I.it%)
I
PHARYNGITIS I SORE THROAT> D D I D 0 l l 1
0.OXI o. OX) I ( 0.0Y.I C o.o;o ( 1.4%) l.ltXI l.it%1
' '
(
I
COUGH 0 D I 0 0 1 1 l
0.OXI C o.o;o I , o . o:o 0.07.1 C 1.4)0 l.4)O
HENIC ANO LYMPHATIC 0 0

I
I 0
' 0 l
' 1
I 1.4%1
l
o.o:o C o.o:o I 1 0.0Y.I C 0.0i!I ( l.4XI 1.4%1 1.47.1
LYMPHADENOPATHY, CERVICAL 0 D
I
I D 0 1
' 1
' 1
O.D7.1 o.ox1 I 1 0.07.) D.Oi!I ( 1.47.1 ( 1.47.1
,DIGESTIVE SYSTEH 2
' l 2
' 2 2 1
( 1.47.1
2.87.1 ( 4.27.1 2.87.) ( 2.87.1 2.87.1 1 .4i!I "

'
( !l.6i0
'
{
DIARRHEA 0 1 1 0 0 0 l
0.07.1 ( 1.4ZI I 1.47.) C D.0i!I I ,.ox, C o.ox, I 1.47.J
NAUSEA 2 2 l 1 1 1 l
2.87.) ( 2.87.1 C l.4ZI ( l.47.1 ( l.4Y.I I 1.4Y.J I 4.27.1
VOMITING 0 (I D 1 1 1 1
0.0)0 ( 0 . 0lO C 0.0)0 ( 1.47.) ( 1.4)0 I 1 .4Y.) I 1.47.1
DIMINISHED APPETITE 0 l l l 0 0 l
o.ox1 I 1 l.4Y.I I l.47.1 ( 1.47.) C •• 07.) C (1.07.1 I 1.47.1
I
OTHER 0
0.0iO
I
I I
0
0.02) ( •
0.0%) (
0
0.07.1 I
1
1.47.I
0
(I. Iii! I I
1
l.it%1
NERVOUS SYSTEN 0
I
I l 1 l 0
' 0 1
0
0
11.0:0 I 1 1.4)0 ( 1.4::1.1 ( 1.lt::I.) I 0 .07.1 ( a.11?.1 ( l.4%1 C:
lit
..0
...
Table 1 (cont)
PATIENT COUHT CLINICAL COMPL~tNTS

REtotlBltlAITT HEPATITIS B VACCINE
STUOY 0869
TIIUTl1ENT
LOT NUIIBEI! Cl217
DOSE 10 t!CG
PATIENT CLASS HE ALTH CARE PERSONNEL
I TOTAL VACCJHEES I 71 PATIENTS-I - OOSE 2 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I HUt1BEI!
CLINICAL
COMPLAUUS
1----------------------------------------------------------------------------
I O I l I 2 I 3 I 4 I 5 I
I WITH
ICOMPLAIHTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••• ••••••••••• l•••••••••• l•••••••••••••••••••••l••••••••••I••••••••••
I I I I I I I I
PAl!ESTHES U S I O I l I 1 I l I o I a I I 1
I I o . OXI I I 1.47.1 I I 1 .4XJ I I 1 .47.J I I 0.0%1 I I O.DXJ I I ( 1.47.1
-----------------------------------1----------1----------I----------I----------I----------I----------I----------I-----------
PEl!SOHS WITH COMPLAINTS I 1l I 9 I 6 I 3 I 4 I J I I 18
I I 18.JXJ I c 12.Tl,J I < 8.57.1 I 1 4 . 27.1 I < 5.67.l I t 4.27.1 I I c 25 . 47.1
-----------------------------------1----------l----------1----------•----------1----------•----------I
PERSotlS WITK HO COMPLAINTS I 58 I 62 I 65 I 68 • 67 I 68 I ----------I-----------
• 53
I c a1.n1 I 1 87. J:t.J I I n.sx, I 1 9s.ax, I , 94.47.1 I , 95.a:o I I , 74.67.1
-----------------------------------1----------
PERSOIIS Nlllt NO DATA I O
I----------I----------I----------I----------I----------I
I O I O I O I O I O I ----------II-----------
0
I I 0. 01.1 • I 0.07.) I I O. OXI I I 0 . 07.1 I I 0 . 07.l I I 0.07. 1 I I I 0 . 07.I
0
0
&:::
·O
0
-
Table 2
PATJEHT COUNT NAXINUt TEHPERATURES
REC0t18IHANT HEPATITIS B VACCINE
STUil 01169
TREATNEHT
LOT .U18ER CLU7
DOSE 1D HCG
PATIENT cus·s HEALTH CARE PfRSONfEL
I TOTAL VACCIHEES ( 71 PATIENTS) - DOSE 1 I

I1---------------------------------------------------------------------------------------I
DAYS POST VACCINATION I NUltBER
l---------------------------------------------------------------------------------------1
....,.......
t1AX TENPERATURE WITH
IDU F, ORAL) ID I
,
1 I 2
, I 3 I
, 4 Is
,I
,
I
,
I HAX TEHP
•••••••••••••••••••••••• .......... I .......... I .......... I .......... I.......... I ........•. I •......... ......•.•• ,
NOlfflAL l I 1 I l I l I 1 I 1 1
1.U!I I ( l.4Y.I I f 1.s1.1 I , l.4:1.) I ( l.4i0 I ( 1.4l0 l.ltiO
I I I I I
< 99 66 I 66 I 63 I 62 I 64 I 611 54
'1't.JY.> I , 94.JY.I I , 92.6:t.l I c 89,9:t.l I , •2.ex, I , ,s.a:o I 76,liO
I I I I I
99 - 99.9 2 I 3 I 4 I 5 I 3 I t n
2.,1.1 I , 4.3Y.I I I S.9l'.I I I 1.2:0 I 1 4,3i0 I I 2.81.) 18. 31.1
100 - 100. 9 I 1 I o I o I 1 I 1 I o I I 3
I 1 1.1tY.1 I , o.o;o I 1 0.01.1 I , 1.4:o I I l.t+Y.> I , 0.01., I I , 4,2;0
------------------------1----------l----------1----------l----------l----------l----------1---------------------1-----------
TEHPERATURE TAKEH I 70 I • 70 I 68 I 69 I 69 I 71 I I 71
I 1 98.61.J I , 98,6:'.I I 1 ,s.e:1.1 I , 97,2Y.I I 1 97.2,0 I noo.01.1 I I 1100.01.1
------------------------l----------l----------l----------l----------l----------1----------1---------------------
nHPuuURE NOT TAICEN I 1 I 1 I 3 I 2 I 2 I o I
l-----------
I o
I I 1.41.) I I J.4,0 I I 4.2:0 I I 2.81.) I I 2.8Y.) I ( o.o;o I I I O.OY.)
0
0
.s:,
-
-0
Table 2 (cont)
PATIENT COUff MAXI ..... TEMPERATURES
RECOHBINAHT HEPATITIS 8 VACCINE
STUOY 0869
TREATMEHT
LOT tM1BER CLU7
DOSE 10 t1CG
I TOTAL VACCIHEES I 71 PATIENTS) - DOSE 2 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I N\Jtt8ER
nAX TEMPERATURE
COEG F • ORAll
1---------------------------------------------------------------------------------------I
I Cl I 1 I 2 I l • 4 I 5 I I
MITH
I NA>< TEHP
•••••••••••••••••••••••••••••••••••1•••••••••••••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
• I I
HOIU1Al I 1 I 1 I 1 I 1 I l I 1 I I l
1.4:1.J I C 1.4:1.) I I l.5i0 • l 1.s;o I I 1.4%) I I 1.s;o I I C 1.4)()
I I I I I I I
< 99 I 61 I 6ft I S& I 61 I 6S I 59 I I 57
90.0%) f I 92.8%) I I 86.61.) • I 92.6i0 • I 92.9%) I I &9.4:t.l I I C 80.3)()
I I I I
99 - 99.9 I 5 I J I 7 I 3 • 3 I s I I 11
1.11., I 1 4.17.> I 1 10.1+1.1 I 1 4.1t1.1 I r 4.1;0 I 1 7.6::<l t t, 1s.sx1
I I I I I • I
100 - 100. 9 I 1 • 1 • 1 I 1 I 1 I 1 I • 2
I I 1.4:o f I 1.4i0 I C 1.5)() I I 1.5)(1 I I 1.4Y.I I I 1.5)() I • C 2.e;o
------------------------l---------t----------•----------1----------l----------1----------1---------------------•-----------
TEHPERt.T\IRE TAKEN I 70 I f>9 I 67 I 68 I 70 I 66 • I 71
I 1 ,e.,;,o I 1 97.27.J I t 94.4Y.J I c 95.&Y.I I 1 98.6Y.t I , ,1.ox1 • • uoo.ox1
------------------------l----------l----------t----------l----------l----------1----------1---------------------I-----------
TEHPERAT\IRE HOT TAKEN I 1 I I! • 4 I 3 I 1 I s I I o
I I 1.4?.J • I 2,8:t.J I t 5.6Y.I I I 4.2Y.I I I 1.41.l I I 7.0lO I I c o.o;o
0
0
I:>
-4
N
._
,....
,....
a)
►
0
:::>
1-
(/)
Study 877

recombinant hepatitis B vaccine among healthy adults
who are negative for hepatitis B virus serologic
markers.
VACCI NE: Yeast Recombinant Hepatitis B Vaccine

Lot 979/C-K.564 (10 mcg HBsAg/ml)
PRI~ARY Professor Oon Chong Jin

INVEST[GATOR: University Department of Medicine I
Singapore General Hospital
Singapore 0316
Republic of Singapore
SECONDARY Dr. Richard Guan

INVEST[GATOR: University Department of Medicine I
Singapore General Hospital
Singapore 03H
STUDY LOCATION: Singapore General Hospital

Singapore 0316
DATE STUDY INITIATED : January 26 , 1985
STUDY POPULATION: The study population consists of 25-30 healthy adults

of either sex (excluding pregnant women), who are
negative for HBsAg, anti-HBc and anti-HBs, have a
nonnal ALT level and have not previously received any
hepatitis B vaccine .
23931/851/1
1/3/86
Study 877

HBsAg) intramuscular injection of vaccine at o.
1. and
and any local or systemic complaints for five days

approximately two weeks before the first injection of
at 1, 2. 3, 6, 8. 12 and 24 months.

anti-HBs, and ALT. Samples may be assayed for yeast
antibody. In addition, samples w1th an anti-HBs titer
>25 mlU/ml may be tested to determine anti-a and ant1-d
subtype specificity. - -
RESULTS: HEALTHY ADULTS

10 mcg Lot 979/C-K564 at 0, 1, and 6 months.
Injection No.
_L_ _2_ J _
31 31 31
Sero logic data at 7-8 months are available for 29

study participants. Inmune responses to vaccine
were measured using an enzyme-linked immunosorbent
assay (ELISA) to detect anti-HBs antibody. At 7-8
months 97% ( 28/29) of vaccine recipients
seroconverted {mIU/ml ~2.1} and developed
protective levels of anti-HBs (mIU/ml ~10). The
GMT for all vaccinees was 508.9 mIU/ml. Among
responders with a titer of mIU/ml ~10 the GMT was
663. 7 mIU/ml. Anti-HBs responses at 1 through 7-8
months are included in Table 1.
23931/851 /2
l /3/86
00495
Study 877
RESULTS: (Contd) 3. Clinical Complaints:

No serious or a laming adverse reactions
23931/851 /3
l /3/86
Study 877
Table 1
Antibody Responses* Among Initially Seronegative Healthy Adults

Following Vaccination with 10 mcg Doses of
Yeast Recombinant Hepatitis B Vaccine
Lot 979/C--IC.564 at 0, l, and 6 Months in Study 877
I with Anti-HBs r.1111 fmlU/ml \

Time All ResDonders
(Months) mlU/ml ~2.1 mIU/ml ~10 Vaccinees mIU/ml ~2. l mlU/ml ~,c
1 0 (0/31) 0 (0/31) 0.3 -- --
2 48 (15/31) 32 ( 10/31) 2. l 16.4 26.9
3 71 ( 22/31) 5S (17/31) 6.1 21.0 28.7

6 77 (24/31) 65 (20/31) 12. l 35.5 49.4
7-8 97 (28/29) 97 (28/29) 508.9 663.7 663.7
"' ELISA
23931/851/4
1 /3/86
0
00
c:o
►
Q
.::,
t-
C.I)
00497

Study 880

personnel who are negative for hepatitis 8 virus
serolog1c markers.

Lot 819900/18066/C-l21S (10 mcg HBsAg/.5 ml)
lot 81766B/18067/C-l216 (10 mcg HBsAg/.5 ml)
lot 81991D/18068/C-l217 (10 mcg HBsAg/.5 ml)
lot 81992A/18070/C-l219 (10 mcg HBsAg/.5 ml)
Lot 819541/18071/C-L220 {10 mcg HBsAg/.5 ml)
PRIMARY Gary P. Wonnser, M.D.

INVESTIGATOR: Department of Infectious Diseases
West Chester County Medical Center
Macy Pavilion
208 S.E.
Valhalla, New York 10595
SECONDARY Katherine Small, M.O.

INVESTIGATOR: Robert L. Yarrish, M.D.
West Chester County Medical Center
Macy Pavi 1ion
208 S.E.
STUDY LOCATION: West Chester County Medical Center

Macy Pavilion
207 s. E.
DATE STUDY INITIATED: April 1, 1985
2391 I/1
1/17/86
00498
Study 880

health care personnel of either sex (excluding pregnant
women), who are negative for HBsAg, anti-HBc and
anti-HBs, have a nonnal ALT level and have not
previously received any hepatitis 8 vaccine.
STUDY PROCEDURE: Health care personnel are assigned to one of the five
lots of vaccine, stratified by sex and age, to assure
that recipients of each lot are simi1ar. Approximately
fifty persons are assigned to each lot of vaccine.
Eligible study participants receive a 0.5 ml (10 mcg
HBsAg) intramuscular injection of one of the five lots
of vaccine at O, l and 6 months. Yacc i ne recipients
record their temperature and any local or systemic
complaints for five days after each injection of vaccine.
Blood samples are obtained from each study participant
vaccine. Post-vaccination blood samp·les are obtained at
1, 2, 3, ~. 7/8, 12 and 24 months.
All serum samples are assayed for HBsAg, anti-HBc, and
ant1-HBs. ALT testing is performed on all
pre-vaccination and 2 month post-vaccination samples.
Samples may be tested for yeast antibody. In addition,
samples with an anti-HBs titer~ 25 mIU/ml may be tested
for anti-~ and anti-~ subtype specificity.

10 mcg Lot 8l990D/18066/C-L215 at 0, 1, and 6 months
10 mcg Lot 81766B/l8067/C-L216 at 0, 1, and 6 months
10 mcg Lot Bl991D/18068/C-L217 at 0, 1, and 6 months
10 mcg Lot 81992A/18070/C-L219 at 0, 1, and 6 months
10 mcg Lot 819541/18071/C-L220 at 0, 1, and 6 months
23911/2
l /17/86
00499
Study 880
RESULTS: (Cont.} 1. Number Vaccinated:
Injection No.
Lot _l_ _ _
2 _3
C-L215 48 48 40
C-L216 43 43 24
C-L217 53 53 26
C-L219 46 46 25
C-L220 43 43 38
( lot C-L215), 24 (lot C-L216), 23(1ot C-L217), 25
(lot C-L219) and 34 (lot C-L220) study
participants. At 7/8 months anti-HBs responses
are as follows:
GKT {mIU/111}
\ Anti-HBs Positive All Resoonders
Lot SIN ~2.1 mlU/ml ~10 Vaccinees S/N ~2. l 11!U/ml ~10
--
C-L215 100(33/33) 94(31/33) 591.2 591.2 799.3
C-L216 100(24/24) 100(24/24) 1187.6 1187 .6 1181.6
C-L217 96(22/23) 91(21/23) 345.8 ,0 6.4 593.6
C-L219 92(23/25) 92(23/25) 332 . 6 612.0 612.0
C-l220 100(34/34) 100 (34/34) 1012.0 1012.0 1012 . 0
Anti-HBs responses at 1 through 7/8 months are

included in Tables 1-5.
23911/3
l /17/86
00500
Study 880
RESULTS: (Cont.) 3. Clinical Results:

Clinical follow-up data are available for 233,
221, and 99 study participants following the
first, second and third injections of vaccine,
respectively. Cl i ni ca 1 complaints and maximum
temperatures reported following each injection are
provided in Tables 6-15.
Clinical % Frequency By Injection No.

Como la int lot l 2 3
Injection C-L215 8(4/48) 13(6/46) 4(1/24)
Site C-l216 9(4/43) 5(2/43) 9( l /11)
C-l217 11(6/53) 4(2/53) 0(0/17)
C-L219 17(8/46) 9(4/46) 6(1/17)
C-L220 0(0/43) 9(4/43) 7(2/30)
Systemic C-L215 2(1/48) 2(1/46) 4(1/24)
C-L216 17(8/43) 2(1/43) 0(0/11)
C-L217 1317/53) 4(2/53) 0(0/17)
C-L219 9(4/46) 0(0/46) 6(1/17)
C-L220 7(3/43) 5(2/43) 3(1/30)

ALT Elevations
One subject whose pre-vaccination ALT level was·
normal had a transient elevated level of this
enzyme at 2 months post-vaccination. A follow-up
serum sample obtained l week later showed a
decreasing ALT. A reason for the ALT elevation
was not ascertained. The subject has not
developed anti-HBs after two injections of vaccine
and has not been reported to show any clinical or
serolog1c signs (HBsAg or anti-HBc) of hepatitis 8
23911/4
1/17/86
00501
Study 880
RESULTS: (Cont.) HBV Markers {Anti-HBc}

In two subjects . the 6 (C-L219) and 8 (C-L220)
month post-vaccination serum samples,
respectively, were borderline positive for
anti-HBc . All previous serum samples were
negat i ve for anti-HBc. The t wo subjects developed
anti-HBs at 1 and 2 months , respectively. Both
subjects have remained HBsAg negative and there
has been no report of clinical illness.
Events Reported to OoBRR
A 25 year-old female subject recorded a
temperature of 100.1°F several days after
administration of a second injection of vaccine
(lot C-L215). A CBC completed at that time
revealed a normal WBC with a nonnal differential
but a platelet count greater than 1 x 106/111113
was noted. Bone marrow examination revealed
numerous megakaryocytes. A pre-existing
myeloproliferative disorder is considered the most
likely diagnosis.
23911/5
1 /17/86
Table 1
Antibody Responses Among In1t1ally Seronegat1ve Health Care Personnel Following

Vacc1nat1on w1th 10 mcg Doses of Yeast Recombinant Hepatitis 8 Vaccine
. Lot 8l990D/1B066/C-L215 at O. 1, and 6 Months 1n Study 880
,; with Ant1-H8S GMT {mIYfml)

Time All Resoonders
{Months) S/N ?:. 2.1 mlU/ml ?:. 10 Vaccinees S/N?:. 2.1 mlU/ml ?:. 10
l Month 24 (l 1 /46) 13 (6/46) 0.9 12.5 33.0

2 Months 76 (32/42) 50 (21/42) 11. l 30.0 77.5
3 Months 86 (32/37) 73 (27/37) 31.9 58.7 95.4
6 Months 86 (31/36) 64 (23/36) 23.0 36.8 71 .8
7/8 Months 100 (33/33) 94 (31/33) 591.2 591.2 799.3
23981/8
8
~
1 /28/86 N
Table 2
Antibody Responses Among Initially Seronegat1ve Health Care Personnel Following

Vaccination with 10 11cg Doses of Yeast Recombinant Hepatitis 8 Vaccine
Lot 817&6B/18067/C-L21& at 0, 1, and 6 Months 1n Study 880
I with Ant1-H8s GMT (mTU/111

Time All Resoonders
(Months) S/N ~ 2 .1 mlU/ml ~ 10 Vacc1nees S/N ~ 2. 1 mlU/ml ~ 10
l Month 20 (8/41) 7 (3/41) 0.7 9.3 39.6

2 Months 86 (32/37) 65 (24/37) 14.4 25.2 45.4
3 Months 86 (25/29) 76 (22/29) 18.7 34.2 45.7
6 Months 100 (22/22) 100 (22/22) 51.5 51.5 51.5
7/8 Months 100 (24/24) 100 (24/24) 1187.6 1187.6 1187.6
23981/9 0
C
1/28/B6
~
w
Table 3
Antibody Responses Among Initially Seronegative Health Care Personnel Following

Vaccination with 10 mcg Doses of Yeast Recombinant Hepatitis B Vaccine
Lot B1991D/18068/C-L217 at 0, l, and 6 Months in Study 880
~ with Anti -HBs GHT {mlU/ml)

Ti me All Resoonders
(Months) S/N?:. 2.1 mIU/ml ?:. 10 Vacc1nees 5/N?, 2. 1 mlU/ml ?:. 10
l Month 19 (10/52) 8 (4/52) 0.8 14.5 91. 2

"
2 Months 75 (36/48) 58 (28/48) 12. l 33.6 58.8

3 Months 84 (32/38) 68 (26/38) 23.6 48.7 77.4
r, Months 87 (26/30) 77 (23/30) 27.5 53.5 69.7
7/8 Months 96 (22/23) 91 (21/23) 345.8 476.4 593.&
23981/10 0
0
1/28/86 ~
.a:,
Table 4
Antibody Responses Among Initially Seronegat1ve Health Care Personnel Following

Vacc1nat1on with 10 mcg Doses of Yeast Recombinant Hepatitis B Vaccine
Lot Bl992A/18010/C-L219 at 0, 1, and 6 Months 1n Study 880
i with Ant1-HBs GMT (mlU/ml)

Time All Resoonders
(Months) S/H ~ 2.1 mlU/ml ~ 10 Vaccinees S/N ~ 2.1 mlU/ml ~ 10
l Month 22 (10/45) 9 (4/45) 0.7 10. 7 36.7

2 Months 64 (27/42) 40 (17/42) 6.3 27.2 69. l
3 Months 66 (21/32) 59 (19/32) 9.5 51.1 63.9
6 Months 90 (27/30) 73 (22/30) 29.7 48.0 77 .2
7/8 Months 92 (23/25) 92 (23/25) 332.6 612 .o 612.0
0
0
23981/1 l g
'-"
1/28/86
Table 5
Antibody Responses Among Initially Seronegative Health Care Personnel Following

Vaccination with 10 mcg Doses of Yeast Recombinant Hepatitis B Vaccine
Lot 819541/1B071/C-L220 at 0, 1, and 6 Months in Study 880
~ with Ant1-H8s GMT lmIU/ml

Time All Resoonders
(Months) S/N ~ 2 .1 mIU/ml ~ 10 Vaccinees S/N ~ 2.1 mIU/ml ~ 10
1 Month 40 (17/43) 21 (9/43) 1. 7 14.6 63.8
2 Months 84 (36/43) 60 (26/43) l&.6 30.& 60.8

3 Months 97 (34/35) 83 (29/36) 50.5 55.6 84.8
& Months 97 ( 31/38) 89 (34/38) 39.S 43.2 53.l
7/B Months 100 (34/34) 100 (34/34) 1012.0 1012.0 1012.0
23981/12 g
1/28/8£,
~
a,
Table 6
PATIENT COUNT CLINICAL COMPL AINTS
RECOMBINANT HEPAllTIS B VACCINE
STUOV 1· 0880
TREATMENT
LOT NUMBER CL215
OOSE 1 10 MCG
TOTAL VACCINEES ( PATIENTS) - DOSE I
I
48
----------------------------------------
OAVS POST VACCIN ATION NUMBER
CLINIC AL ------------- --- - - ------- -- ------------------------------------------------- WITH
COMPLAINTS 0 I 2 3 4 I 5 COMPLAINTS
•• •• •••••••••• ••••••••••••••••••••• .......... 1.......... I·········· .......... ···· ······ 1·········· 1·········· ......... .
,ON , LOC AL (INJECT. SITE)
2.1I ,r. ) ( 3
6.31' )
I ( 2.,,., (
I I I 2.,1,. ,
---------- ---------- ---------- ---------- ----------,---------- ---------- -----------
( 0
0.0"- l II ( 0 .O
0%) (
4
B . 3 11. )
·.,an NESS o o o o
'
2.1 ,r. ) (
2
4.2,. ) ( o . Oll.) II ( o.oll. ) J c o.oll. >
I
c 0 . 0,r. 1 I c
3
s.311. J
o I o o I
~ENOERNESS
____ o·:" >_
1
_c __ 2 . : " >__ <__ 2·: • >
1
-1- c__ 1
2 · : " >__ c__ o·:">__ <__ o · : " >_, __________ ,_ c__ 2 ·:">
1
t~I( 1
I
o.o,r. J I c 2 . 1,. , c 2.,,., I c 2.1 ,. , c o.oll. J c 0.01' ) I I c 2.,,.,
BUOY/GENERAL 1 0 0
.•, 1t>l,. l I 0
I 0 1
o.o,. ,
I '"l
( 0,0,') ( o.~,. , ( 0. 0"-) ( 0.0%) ( 2. , ,. )
2.
FATIGUE/WEAKNESS I 0 1 0 0 0 0 ,.
o.o,. , ( 2. , ,. , 0.011. ) ( o . o,. , ( 0, 01') ( o.o,. , ( 2. , ,. )
ILLNESS, NOS I 0
o.o,. , (
1
2 , , ,. ,
0
o,o,. , (
0
0,0,. ) (
0
0 .Oll. ) (
0
0.:,. , I (
1
2 . , ,. ,
RESPIR ATORY I 0
0. 0 ,. ) (
0
0,0,. )
I
2. \ 'A, ) (
I
2. , ,., ( o_g,., I c o .o'4 l I
I
I (
l
2 . , ,. ,
I I I
RHINITIS I
I <
O
o.o,. ,
Ic 0
o.o,. ,
1
2 . 1'- ) (
1
2. , ,. ) ' (
0 I
o,o,. , I (
0
o.o,. ,
I
I <
l
2. I!, )
-----------------------------------1----------1----------
PERSONS WITH COMPLAINTS I 1 ( 4
----------
2
----------
2
----------1----------
0 0 ---------- -----------
5
I c 2,1 ,. , I c a.3,. l 4.2") ( 4 . 2,. ) ( o. o,o I c 0. O'I ) ( 10 . 4 ll. )
-----------------------------------1----------1----------
PERSONS WITH NO COMPLAINTS I 47 I 44
----------
-46
----------
46
----------
-48
----------
48
---------- -----------
43
I c 97 . 9 11. J I < 91.1,. , ( 95.8") ( 95.H) (100 . 0ll. ) ( 100 . o,r.) ( 99 . 6 '- )
-----------------------------------1----------1----------
PERSONS WITH NO DATA ·1 0 I 0
----------
0
----------
0
----------
0
----------
0 ------ .---,-(--0.~~,--
c o,o,. > I c o.o,. > O.Oll. ) ( 0 . 0,. ) C O.O~ ) I ( D. O~ )
0
0
I.fl
0
--.I
Table 6 (cont. )
<. ruov D880
Tl'E~l MENT
U, T Nl1M8ER CL215
nose 10 MCG
I-------------------------------------- -------- ------------------------------

1
TOT AL VACCINEES ( 48 PATIENTS) - OOSI: 2
OAVS POST VACCINATION NUMBER
~4
"!J NIC AL
·•
,;,41'l ~ I HTS
•••••••••••••••••••••••••••••
I!-------------~
O I -----------
••••••••• •
I
-------------------------------------------------
I
•••••••••• :
2
••••••••••
I 3
•••••••••• !••••o••••• I••••••••••
••••••• • ••
4
••••••••••
5
WITH
COMPLAINTS
6
:11~ . _LOCAL-(JNJECT._srre> ___ _ _ !_ <__ e.~,., _1_< __ 6 _~,., _!_< __ 4 _~,.>__ <__ 2 .~,. >__ <__ 2 .~,. , __ <__ 0 _g,. >_l----------,-- ---------
13 . 0 ,. )
" NENESS
(
4
8 , 7,. ) (
3
6 , 5,. )
I( 2
4.3,. ) ____ 2.~ ,. , __ <__ 2 . ~,. , _1_ <__ o_g,. ,_1 ____ ______ ,_ 1_,3 _~,.> __
----------------------------1----------
,: I I
----------1----------
O I D I 0 0 o I I 1
I < 2,2,i ) < o.o,. J I c 0 . 0 ,. 1 t 0 . 0%) 0.0%) o.o,. > I I c 2. 2,. ,
1
'"': l •RV
-:, l'ER HESPJ JI ATOAV INFECT. , NOS

I
2. 2%)
1
0
0.0%)
0
0
0,0,C.J
0
o.~,.,
0
I(
. 0
0
o,o,.,
0
0 , 0 ,. )
0
1
2 . 2 ,.. )
1
2,2,. , 0.0%) 0. 0%) 0 . 0" ) 0.01') 0 . 0" ) 2 . 2!1.)
1·,,1 :;oNS WITH COMPLAINTS I

(
5
10.9" )
3
6 , 5 ,. ) (
2 I( ,
4 . 3,. ) 2 . 2%)
I
2 . 2%)
0
o.o,., (
6
13.011. )
n n~ uNS WITH NO COMPLAINTS I

--------
41 43
----------1----------
44 I 45 45 46
--------
40
( 89. , ,., ( 93 , 5 ,. ) _c_95_1,., _ _<_91 .e,. ,_ ( 97.8") ( 100. 0 11. ) ( 67 . 0 ,. )
1-'tH~llNS WI TH NO DAT A I
--------0 0 0 0 0 0 0
0. 0 ,. ) _O , O,_ J ( o,o,., 1 ( 0.0,. ) o. o,i > o.o,., 0 . 0 ,. )
0
0
1/1
0
01>
Table 6 (cont.}
PATIENT COUNT CLINICAL . COMPLAINTS
'-. "OPY 0880

l"rff.AlMEtlT
I.OT NllMBER CLZ 15
~1\t::>E 10 MCG
I TOTAL VACCINEES ( 40 PATIENTS) - DOSE J I

----------------------------------------------------------------------------1
OAVS POST VACCINATION I HUMBER
' NI C lL
- 1: •1 AINTS
-----------------------------------------------------------------------------1
O I 1 I 2 I 3 I • 5 I
WITH
I COMPLAINTS
· · •·•• •••••••••••••••••••••••••• •••• • •••• •l • • ••••• • •• t••••••• • • •l ••• • ••• • •• 1••••• •• ••• ••••• •• •• •l• • • • • • • • ••I• ••• • •••• •
· , 11•• LOC AL (INJECT. SITE) I O I ' '1 1 I O I O O '1 I
( o.o,., ( 4,2 'Jf. ) ( 4 . 2%) I ( O.O'Jf. ) I ( O.OY. ) ( 0.0Y. ) ( 4.2%)
·.fll~ ;S--- --------------------1------0--- ------,--- ------ ,---l------0---l------0--- ------0---,---------- ------,----
·------------------------!- <__ O.O'Jf. ) - - <__ 4 . 2") - - <__ 4.2%)_,_ <__ 0.0%) __ <__ o.o,., - - <__O.O'Jf. ) -1----------1-(-_4.2%) __
I( 4 . : ,. ) ( 0. g'Jf, ) ( 0. g,.) I ( 0. g,.) ( 0. g,.) ( 0. g") I I ( !") d.
.JUI.JV / GENER AL
'-- ~LA l.iE

•. :,' .)I ( I
.
0.0%)
0
0 o .I
O. O'Jf.)
o
I
I(
I
o
O.O'Jf.)
o
o_g,. >
o
I < o . ~'Jf. >
o
I
, I
I
". 2" )
1
•• 2 'Jf. ) 0. OY.) ( 0 . 0%) I ( O.O'Jf.) O . OY. ) ( 0 .OY. ) 4 . 2 'Jf, )
, I( , ----------,---------- ---------- ---------- ----------

••:. R~l.•NS WITH COMPLAINTS
•.2'J!, ) 4.2%) ' I
4 . 21' ) (
0
0
0 . 0,.)
0 1
O.OY. ) ( 0.0%)
I
4 . 21')
PERSONS WI TH NO COMPLA INTS I

----------
2323
----------
24 ----------1----------
23 24 2-4 23
I ( ( 95.8%)
95.B'Jf. J (100 . 0'Jf.) (100.0'Jf. )
( 95.B'Jf. ) (100 . 0'Jf.) ( 95 . B 'Jf, )
·----------------------------------1----------
I ---------- ---------- ---------- ---------- ----------
PERSONS WI TH NO DATA O 0
I (
0
O. O'Jf. )
0
(
0
O. O'Jf. ) {
0
0. O'Jf, ) ( 0 . 0,. l ( 0 , Q'Jf, ) I< 0 .O'J!,)
0
0 .O 'J!, )
0
0
\II
0
.()
Table 7
PATIENT COUNT NAXIHUN TENPERATURES
llECot191HAHT HEPATITJS 8 VACCINE
STUDY 11880
TREA1l1£NT
LOT tlU18Ell Cl215
DOSE 10 t1CG

1---------------------------------------------------------------------------------------I
1 DAYS POST VACtltlATIOH I HUl18ER
NAX TENPERATUllE
(DEG F, MAL)
1---------------------------------------------------------------------------------------I
I O I I I 2 I 3 I 4 I 5 I I I NAXWITH
TEl1P
a•••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 I 36 I 38 I 35 I 36 I 37 1 37 I I n
I I 80.0:0 I I 8i't.4Y.) I I 79.5:o I I 81.8Y.) I I 88.lY.1 1 I 92.!IY.) I I I 55.6i0
I I I I I I I I
99 - 99. 9 I e I 7 I 9 I e I s I 3 I I 19
I 1 11.e:o I I t5.6Y.> I 1 20.5;0 I 1 111.z;o I 1 11.,1.1 I r 1.s:o I I t 42.u1
I I I I I I I I
100 - 100.9 I 1 I o I o I o I o I o I I 1
I I 2. 2% l I I o. 0% l I t o. OY. l I I o. OY. l I I o. o:o I I O. OY. l I I I Z. ZY. I
------------------------1----------1----------l----------t----------l----------l----------l---------------------l-----------
TEHPERATURE TAKEN I 45 I 45 I 44 I 44 I 't2 1 40 I I 45
I r 93.&Y.I I 1 93.er.1 I 1 ,1.1i, It •1.1:0 I 1 111.!l:o 1 1 &3.3Y.l I I 1 '13.e:o
------------------------l----------l----------l----------t----------l----------1----------1---------------------I-----------
TEHPERATURE NOT TAKEN I 3 I 3 I 4 I 4 I 6 I 8 I I 3
I 1 6.3%) I I 6.3Y.I It 8.3Y.l I I 8.37.l I I 12.SY.I I I 16.7:t.l 1 I I 6.Jin
-"'
0
0
Table 7 (cont.)
PATIEHT COUNT MAXIl1Ut'I TEMPERATURES

RECOMBINANT HEPATIT~S 8 VACClllE
STUDY 0880
TREAlt1ENT
LOT NUtl8ER CL21S
DOSE 10 NCG
I TOTAL VACCINEES ( 48 PATIEHTSI - DOSE 2 I

Il---------------------------------------------------------------------------------------1
DAYS POST VACCINATION I NUmER
MAX TEMPERATURE
(DEG F, ~All
l---------------------------------------------------------------------------------------1
I D I 1 I 2 I 3 I 4 I 5 I I
WITK
I MAX TEMP
••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••t••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 • 3'+ I 35 • 33 I 3S I 3& I 32 I I 28
I I 89.57.J I I 9'+.67.J I( 86.87.1 I ( 94.61.1 I ( 97.JiO I ( 91.41.I I I I 73. T/.l
• I 1 I I I I I
99 - 99. 9 • t+ I 2 I s I 2 I l I 3 I I 10
I t 10.51.J I t S.47.1 I t u.2;0 I , S.4i0 I t 2.11.1 I t 8.61.l I I 1 26.37.1
------------------------1----------1----------t----------l----------l----------l----------l---------------------l-----------
TEMPERATU!lE TAKEN I 38 I 37 I 38 I 37 I 37 I 35 I I 38
I , 79. 21.1 I , 77. u, I , n. 21.1 I 1 77 .1;0 I t n .11.1 I , n. 91. I I I < 79. 2x,
------------------------l----------t----------l----------t----------t----------l----------t---------------------l-----------
TEt1PERATU!lE NOT TAJCEN I 1D I 11 I 10 I 11 I 11 I 13 I I 10
I ( 20.8i!I I ( 22.97.I I ( 20.81.I I ( ZZ.97.1 I f 22.97.1 I l 27.17.) I I ( 20.8XI
.::,
--
0
:JI
Table 7 (cont.)
PATIENT COUtlT HAXlt1Ur1 TEt1PERATURES
RECot18IIU NT HEPATITI,S 8 VACCINE
ST\JDY 0880
TRE.& lt1ENT
LOT NUl'IOER Cl21S
DOSE 10 HCG
I TOTAL YACCINEES ( 40 PATJEHTSI - DOSE 3 I

1---------------------------------------------------------------------------------------
I DAYS POST VACCIHATIOH
I
I NUMBER
HAX TEHPERAlU!E
I DEG F, OllALI
1---------------------------------------------------------------------------------------I
I O • 1 • t I 3 I 4 I 5 I I
MITH
I t1A)( TEIIP
•••••••••••••••••••••••• l•••••••••••••••••••••l••••••••••l•••••••••• l•••••••••• l••••••••••l•••••••••• I•••••••••• •••••••••••
I I I I I I I •
< 99 I 11 • U I 13 I 10 I 13 I 11 I I 11
I t 78. 67.) I t 9t . 97.) I ( 92.9:0 I I 76.9;1,I I I 92.9;1,I I C 91.TI.) I • ( 57.li()
I I I • I I I I
99 - 99. 9 I 3 I l I l I 3 I l I l I I 6
I ( 21.47.) I C 7.17.) I C 7.lin • C 23.1%) I I 7.i;o I I 8.37. J I I ( 42.9i0
--------------------·
TEHPER.& TU!t
TAKEN
---l----------l----------1----------l----------1----------l----------l---------------------•-----------
I 1~ I 1~ I 14 I 13 I lit I 12 I I 14
I 1 35 . 07.I I c 35.07.1 I I ls.oz, I c 32.s;o I 1 35.o:o I , 30 . oz, I I 1 35.or.,
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEMPERAT\JRE NOT TAKEN I 26 I 26 I 26 I 27 I 26 I 211 I • 26
I I 6 5 .0Z) I I 65.0Z) I I 65.0Z) I ( 67.SZI I ( 65 . 07.) I 1 70.07. 1 I I I 65 . 0%)
0
0
-
VI
IV
Table 8
PATIENT COUNT CLINICAL COMPL AINTS
:,-r uov 0880
TRf/lTMENT
~ ,-,T tlll""B~A CL216
rF l~1 f. 10 MCG
- I - --------------------------------------------------------------------------------
TOT AL VACCINEES I 43 PATIENTS) - DOSE 1
f--------------------------- -------------------------------------------------
1 DA YS POST VACCINATION NUMBER
!tll(AL
. •.Ii l A J NTS
1---------------------------------•--------------------------•---------------
I O I 1 I · 2 I 3 I 4 I 5 WITH
COMPLAINTS
· · ' ' ~••• •••••••••• • ••••••••••• • •• l • •• ••••••• l• •• •••••• •I ••••••• •• • •••••••• ••I•• •••••••• ••••••• ••• •••• 0 ••••••
••••••••••
· · tnH . LOC AL (INJECT . SITE) I 2 I , l o l 0
0 . 0 '!I. )
0
o. 0 '4 )
4
9.J ,r. J
.r~rss-----------------------1-c--::;:: - -:--::;: :- '1-:--::~:-1-:--::::- -,--,.~, ,-i-,--, .~, ,-•---------- 3

7 . O" l
.,,,Hir.ess 0 1 1 0 IO Of O 1
o.o•o c 2 . J "' l I c o.o"' > c o.o"' > < o.o"' > I I o . o ,r, J ( 2 . 3 '!1. )
J
I
, ,. 1 THHI A ( REOHE SS 1 o I 0 0 0 0 1
2. 3 '!1. ) 0 . D'!I.) I 0 . O'!I. ) o.°"'> 0.0'!1. ) 0 . 0 "' ) 2 . 3,r. )
I
---------- ---------- ----------I---------- I----------, --- -------

: ;1 lLL I NG I 0 0 1
2. 3"' ) 0.0"' 1 ( 0.0'!1. ) ( O.Q,i.J
o ( 0.0'
o !1. ) ( 0 .0
o '!1. J ( 2. 3,- J
~YSTE.Mlt I 2 3 2 3 I 0 8
I c 4. 1"'> 7 . 0 '!I. ) ( 4. 7" ) ( 1.0,r, ) I ( 2 . 3'!1. J I < o .o,r. J ( 18 . 6 '!1. )
- --- ---------------------------------------------------------------------------- ----------------------
•JtiOLE BOOV /GENER AL I 2. (
1
31' ) ( 4.7")
2
(
0
0. 0 1' ) I ( II
1
2 . 3 1' ) (
0
0.0,. ) ( o . ~ ,. > (
3
7 . 0 ,. )
I
I
~WEATlf-4G 1 0
O.O'l )
2. 3,r. )
0 I 0 0 0 1
O.O'l ) ( 0.0',I,)
F ATIGUE/WEAKNESS
C
0
C
I 0
(
0
( 0. O'l )
0
(
0 . :") I ( 2 . 3 11, )
1
( 0. O'l ) ( 2. 31') ( o . o ,r. ) ( o . o,r.) . ( O. O"' ) ( 0 . 0 '!1. ) ( 2.3 ,. )
HEADACHE
(
0
0.0,. ) ( '
2.3,. J (
0
0. O" ) (
1
2 . 3 ,. ) r
0
o. o,. > I
I (
0
0 . 0 '!1. ) (
2
4 . 7 '11, )
RESPIR ATOR'(
I
(
0
0.0"' ) (
I
2.31' ) II c '
2 . 3 ,r, J I c
I
3
7.0,. ) (
0
0. O'!I. )
I
I
I
(
0
0,0'4) (
3
7 . 0 ,. )
FlHINITJS 0 0 I
( 0.01' ) ( 0.01' )
I' 0.H)
0
I (
2
4. 7 '!1. ) (
0
0 . 0 ,. ) I (
0
D . O'!I. ) (
2
4. 711,)
-
0
\11
V4
Table 8 (cont. )
:nuov 0880
lREATMENT
LOT NUMBER CL2HI
OOSE 10 MCG
-- - ----
-----------------------------------------------------------------------------------------------------
TOTAL 1/ACCINEES ( 43 Pl,TJENTS) - DOSE I
CLINICAL
COMPLAINTS
I
----------------------------------------------------------------------------
----------------------------------------------------------------------------
I ' I 2 I 3 I "' I s ,......... . COMPLAINTS
••••••••••••••••••••••••••••••••••• ....•••.•...••••.........•..••......•..•••..................
0
NUMBER
WITH
..........
PHARYNGITIS (SORE THROAT) o
o. o,i,> I
I 0
0.011.)
0
0. OY.) '
2.311.)
0
O.OY.)
0
0 . 01')
I
2 , J,r.)
I
UPPER RESPIRATORY INFECT .• NOS o I I I ,
o. o,i,J I
I
2 . 3%) 2.31') '
2 . 31')
0
0. 0,.)
0
0.01')
I
I 2 .311.)
MUSCUI.OSKELETAL I
I I 0 0 0 0 0 I I
2.3%) 0.011.) o. o,i) o.o,., 0.0,.) o. o,i) I 2.3,r.)
ARTHRALGIA (OTHER)
DIGESTIVE SYSTEM
2 . :,. ) I( 0
0.01')
2
0
0.0'1O
2
0
O.OY.)
I
0
0. OY.)
I
0
0 . 0,.)
0
I
I
I
II
I
2.J'l)
4
o.o,i,) I < 4.711.) 4. 7,.) 2.311.) 2 .311.) 0.0,.) 9.311.)
DIARRHEA
o.g,o I c
2
4. 7'4)
2
4. 7")
1
2.31')
1
2.31')
0
0.0,.)
I
I
I
I
4
9. 3ll)
NAUSEA 0 0 I 0 0 0 I
O.O'I) ( 0. 0'4) 2. 3,.) '
'IERVOUS SYSTEM
0.01') O.Oll.) 0.0,f,)
II 2.JY.)
'
2.3,.) (
0
0.0'1)
0
0.0%)
.
0
0 .01')
0
0 . 01')
.
0
O.OT.)
.
I
I
I
2 . 311.)
VERTIGO/DIZZINESS I l I 0 0 I .D O ( 0 I I 1
H:RSON!,-WITH-COMPLAINTS------------1-(-- •:")
I c
2
-!-(c__ o.:11.)_
I
_< __ 0.01') _j_< __ o.011.> __ <__ o.o,.>_j_ <__ o.o,.> -1----------1- <__ 2.311.) __
2 I 3 , I o I 9
9.311.) 9 . 311.l c 4.7,.) I c 1.011.1 c 2.3,r,1 < o . o,.> I < 20 . 9'-)
PERSONS WITH NO COMPLAINTS 39 39
----------,----------
41 40 ·
----------
42
----------1----------
43
-----------
34
( 90. 7Y.) ( 90. 7Y.) C 95.3'lH IC 93.0,.) t 97.71') (100.0'l'.l l 79.1'1)
l ..:IIS<mS WITH NO DATA 0 0
----------1----------
0 o ----------
o ----------
o ----------1-----------
I o
0. 0,.) 0.01') c o.0'41 I c o.o'4> c o . o,i,) c 0.011.> I c o.o,.,
0
0
-
"1
~
Table 8 (cont. )
STUOV 0800
TREATMENT
LOT NUMBER CL218
01>~f. 10 MCG
-- -----------------------------------------------------------------------------------------------
I TOTAL VACCINEES { 43 PATIENTS) - DOSE 2 I
1----------------------------------------------------------------------------,
CLINICAL
COMPLAINTS
,----------------------------~~~~-~~~~-~~=~~~~~~~~---------------------------
O 1 2 I 3 5
N~~~~R
I COMPLAINTS
4
••••••••••••••••••••••••••••••••••• •••••••••• •••••••••• ••••••••••!••••••••••'•••••••••• •••••••••• ••••• ••••1•••••••••• 0
UEACTION, LOCAL (INJECT. SITE) I

I (
1
2.311)
- ---INFLAMr.!ATION-------------------1----2.!,.,-
(
0
0,011) {
0
0.0ll) I {
I 0
0 . 0ll) I (
I
I O
0.011) (
I
2,3lll
-(--O.g,.,-(c--·o,g,i,)-1-(--o.g11,-i-c--o.g,.)- -(--O.g11.,- ---------- -(--2.}11.)--
I(
I
I 2
4 , 7'11.)
1
SORENESS 0 0 o I o
o.o,i,J
0 1 I
( 0. 0"-) < o.0'-) I < o . o,r.J o.o,r.) 2 .3,.) I c 2. 3'11.)
I c o.~,., ----------1----------1----------,----------,----------
~~~;~;;c----~---- ------------------1---------- 0 o I
0.0%)
o 1
o.o'll.) I C
1
----------1-----------
o.o'll.J
1 I
2.3'4) 2.3'-) I c 2 ,3'- >
~ -··-----------------------------------------------------------------------------------------------------------------------
I
WHOLE BODY/GENERAL 1 0 0 I 0 0 0 1 1
I 0 . 0'0 0.0'-) ( O.OY,) 0.0%) ( O. MJ ( 2. 37,) ( 2, 3"-)
I
FATIGUE/WEAMNESS I 0 0 0 0 0 1 1
0.011) 3,i,)
Uf::ADACHE.
II 0
0. 07.)
0
( 0 . 011)
0
0.011)
0
( 0.011.)
0
( 2.
I
( 2. 3,i,)
t
o,o,i,J I
,,, 1 l>ATORV
I D.Oll) 0. 0'4) ( 0.011) ( 0.0!0 ( 2. 3%) ( 2. 3"-l
I
0
o.o•>
0
o.o,i,) (
0
0.0'-l
0
O. 0'4)
t
2.3,., II 0.0%)
0 t
2.3%)
JJltl tfl TIS I o 0 0

I ( 0.0ll)
--- ------------------------------1----------
l'!'lhONS WITH COMPLAINTS I ----------
0. 0'4)
----------
( 0 , 0,C.)
_ <__ o·:"> -1- <__ 2.~•>_,_ <__ o·~"'-1---------- _c __ 2·:•> __
_c__ ◄ . 1'-> __
1 0 0
I < 2,3,i,J O.O'll) ( O,Oll) _ <__ o . o,i.i _j_ c __ 2 . J,c.1 _,_< __ 2.J,c.>_l----------
... -·-----------------------------1----------
I ---------- ----------
, •-r• " 'II!\ WITH NO COMPLAINTS 42 43 43 43 I ,n t 42 I ,s1
I c 97.744) 1100. o,n (100.0'1,) _c,oo.o,., -1- C_91 .111>_l_c_91 _1,.1_1 __________ j_<_9s.J'lJ __
-----------------------------,---------- ---------- ----------
' ., WI TH HO DA TA I·· 0
I < o . O'- l
0
0. 0'4)
0
( D.OYt) C
0
o. o-..J
I C
O I
o. 0ll>) I < o. o,r.J I
O 1 I
I c o. o'll.J
O
0
0
....
IJ\
I.II
Table 8 ll.!Ollt.)
S i" IJ [)V 0880
Tl<t:A nlEHT
LOT NUMBER CL216
lHlSE 10 MCG

1----------------------------------------------------------------------------
I DAYS POST VACCINATION NUMBER
CLINICAL
C:OMP LA I NT S
1--------------------------------
I O ) 1 2
--------
) 3
------------------------------------
I 4 ) S )
WITH
COMPLAINTS
i••······························••1••······••1••········
I I ········••1••······••1••·······•1••······••1••·••
I I I I ••••1••········0
Wt AL TI OH. LOCAL (INJECT . SITE) I o I o 1 I o I o I o I 1

c o.O%l I < 0.0%) c 9. 1~> I c o.0%) I c o.o%l I c o. o%l I c 9.1 %l
J_________ -
:',0RENESS
1 1 1 1 1 1 1
''"'""'-.,,_-co•"•'"''------------;_ --•·:" -1- --•·:" -1- --•· : " -1- -- •-~l -1- __o .~l -1- --• · : " --•· :., --
. ·- -------------------------------1- <__ o.o%J -1- c__ o.o~,_,_c __ 9.1%J -1-< __ o.o~>_I_ c__ o.o%>_1_c __ o.o~J -1----------1-c __ 9.1%J __
L•f.~~;ONS WITH NO COMPLAINTS ) 11 ) 11 I 10 I 11 ( 11 ( 11 ) ) 10
I c100.0%J I <100 . 0~1 t < 9 □ . 9%l I c100.0%> t c100.0%l t c100.0%l I I c 90.9~>
-------------------------------1----------1----------1----------1----------1----------1-------
nR•;,)NS WITH NO DATA I o t o I o t o I o t o
--- 1-----
t
----- 1I -----------
o
I < o.o~J I c o. O%l I c o . O%J I I o.o~> I c o. o%J I c 0. 0%) I I c 0.0%)
0
0
-
111
0-
Table 9
PATIENT COUNT HAXI~ TEHPERATURES
RECOt18lHANT HEPATIT,IS B VACCitlE
STUDY oeeo
TREATIIENT
LOT NUHeEI! CL216
OOSE 10 HCG
I TOTAL VACCitlEES I 43 PATIENTSI - DOSE 1 I

1---------------------------------------------------------------------------------------•
I DAYS POST VACCINATION I NUffl3ER
HAX T(H~ERATURE
IDEG f, MALI
1---------------------------------------------------------------------------------------•
I O I 1 I 2 I 3 I 4 I 5 I I I HAXWITH
TEtlP
••••••••••••••••••••••••••••••••••••••••••••••l•••••••••• I•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
I • I I • I I •
< 99 I 33 • 33 I 33 I 30 I 33 I 30 I I n
I I 94.3?.I I I 94.3?.I I I 97.1)0 I C 93.81.1 I (100.0?.) I 1100 . 0;0 I I I 82.'1?.I
I I I I I I I I
99 - 99. 9 I 2 I z I 1 I 2 I o I o I I 6
I , s.1r.1 I , s.T/.1 I I z.91.1 I c 6.31.1 I , o . oz1 I , o.o;o I I , 11.1:0
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TENPERAT\JIIE Tll<.EH I 35 I 35 I 3ft I 32 I 33 I 30 I I 35
I I 81.41.1 I 1 81.4,0 I c 79.lr.l I c 74.41.1 I c 76.71.1 I r 69.e,o I I c 81.41.1
------------------------•----------l----------
TEHPERATURE HOT TAKEH I 8 I 8
l----------l----------l----------l----------1---------------------1-----------
I 9 I 11 I 10 I 13 I I 8
I I 18.6?.I I C 18.6?.J I I Z0.91.J I I Z5.6i0 I c 23.31.J I C 30.2:0 I I I 18.67-1
0
0
-...,
\II
Table 9 (cont. )
PATIENT COUNT HAXIt1Ut1 TEffl'ERATURES
RECOM8IHAMT HEPATITI~ B VACCim
STUJY 0880
TREATHEHT
LOT I-M18ER Cl:?16
DOSE 10 HCG
I TOTAL VACCINEES C 43 PATIEtlTS I. - DOSE t I

l---------------------------------------------------------------------------------------1
I DATS POST VACCINATION I HUtl!!ER
HAX TEHPERATURE
I DEG F, ORALI
l----------------------------------•----------------------------------------------------1
I D I 1 I 2 I 3 I 4 I 5 I I
WJTH
I t1AX TEHP
•••••••••••••••••••••••• l••••••••••••••••••••••••••••••••••••••••••• l••••••••••••••••••••• ••••••••••• l•••••••••• I••••••••••
I I I I I I I I
< 99 I n I u I 22 I 21 I 21 I 19 I I 20
I( ,2.0;0 f uoo.o;o I C 91. 7-:1 I I 95 . 5%1 I C 95.5% 1 I I 90.5% ) I I I 80.o;o
I I I I I I I I
99 - 99. 9 I 2 I o I 2 I 1 I 1 I 2 I I s
It a.01.t • t t . or.1 I c 8.3%1 I c 4.51.1 I I 4 . S1.1 I I 9.51.I I I t 20 . 0;0
------------------------l----------l----------l----------l----------l----------l----------1---------------------1-----------
TEMPERAT\JRE TAKEN I u I tz I 24 I 22 I 22 I 21 I I 2s
I , J &.11.1 I r s1.21.1 I r ss.ar.1 I , s1.2;0 I • s1.27.1 I r 4& . a;o I I 1 58.1:0
------------------------I---------- I----------I----------I----------I---------- I----------I--------------------- I-----------
TE11PERATURE NOT TAKEN I 18 I 21 I 19 I 21 I Zl I 22 I I 18
I t 41 . 91.t rt tta.a;o I c 44.2%1 I I ftB.117.1 I c 48.8l0 I c s1.21. 1 I I I 41.9i0
0
0
...
11'
CD
Table 9 (cont.)
PATIENT COUHT MAXIt1Ult TEMPERATURES
RECOMBINANT HEPATIT)S B VACCINE
511.IDY 0880
TREATMENT
LOT tl\Jl18ER Cl216
DOSI: 10 MCG
I TOTAL VACCINEES I 18 PATIENTS)• DOSE 3 •

1-----------------------------------------------------------.
---------------------------•• Nl.lt1SER
MAX TEMPERATUAI:
IDEG F • lmAll
1---------------------------------------------------------------------------------------•
I O • l I 2 I 3 • It • 5 I I
WIT1l
• MAX TEMP
••••••••••••••••••••••••l••••••••••••••••••••• l••••••••••l•••••••••••••••••••••l•••••••••• I••••••••••••••••••••••••••••••••
I I I I I I I •
< 99 I s I s I 6 I 6 I 6 I s I I s
I I 83.3¼1 I I 8J.3i0 I 1100.0lO I 1100.0%1 I noo.o:;o I (100.0¼t I I ( 83.31/.1
I I I I I I I I
'19 - 99. 9 I 1 I 1 I o I o I o I o I I 1
I I 16.77.1 I I 16.T/. I I I 0.0%1 I I 0 . 07.1 I I O.Oll I I O.Oll I I I 16.71/.1
------------------------1----------l----------1----------l----------l----------1----------1---------------------1-----------
TEffl'ERATURE TAKEN I 6 I 6 I 6 I 6 I 6 I 5 • I 6
I I 33.3% 1 I I 3 3 .3,0 I I 33.37.l I I 33. 3 7.1 I I 33.llO I I 27.8%1 I I I 33 . 31/.1
------------------------l----------l----------l----------1----------1
TEtfPERATURE NOT TAKEN I 12 I 12 I 12 I 12 I
----------1----------l---------------------1-----------
12 I 13 I I 12
I I 66.7,0 I c 66.71.1 I l 66.7ZI I c 66.7ZI I I 66.7% 1 • C 72.2l0 I I I 66.77.1
...
0
In
.0
Table 10
'>""llOV 0880
TRE,..TMENT
t.UT NU~BER CL2t7
OOSE 10 MCG
- --------------------------------------------------------------------------------------------------
TOTAL VACCINEES ( 53 PATIENTS) - DOSE 1 I
----------------------------------------------------------------------------1
OAVS POST VACCINATION I NUMBER
CLINICAL
t:OMPUIINTS
O
1
I 2 3 I 4
•••••••••••• • • • ••••••••••••••••••••l•••••••••• •••••••••• •••••••••• •••••••••• •••••••••• •••••••••• I
----------------------------------------------------------------------------1
5
WITH
COMPLAINTS
••••••••••I••••••••••
RE~CTION, LOCAL (INJECT. SITE) "' I 1 o I o 1 o. 6
( 7 • 5,r, > I c 1. 9,r, > c o. O'll. > I c o. O'I.) c , . 9'11. > ( o. o,r, > c , , . 3,r, >
·--------------------------------1----------1----------
PAIN O O
----------,----------
O I O
----------
1
----------1----------
0 I -----------
1
( 0. 0,.) I ( 0, 0,.) I ( 0. 0,.) I ( 0. 0'1,) ( 1 • 9'1.) ( 0. O'I.) I I ( 1 • 9,r,)
c,ORENESS
·- ---------------------------------,-• __ ,.:,,_!_, __ ,.:.,_,_, __ •. ::.,_[_, __ •. :., -1-,__ •. :., __ ,__ •. :.,_, __________ 1_, __ ,.:.• __
~;v !~T£::MI C I 3 I 3 I 1 I 1 I 2 · o I I 1
I < 5 . 7'1.l I < s.7'1.J I c 1.9'1.J I < 1,9,r,J I < 3.e~> < o.o,r,J I I < 13_2,.,
- . --------------·----------------------------------------------------------------------------------------------------------
1
Ml~Lf BODY/GENERAL I 0 1 1 1 I 0 3
II 0,0ll,) 1.91) I. 9ll,) 1.9%) 1. 9'llo) 0,0,.) s. 7")

--ilUUE/WEAKNESS
,, ~111.C:HE I
o_g,.)
0
I
II
(
(
,·:") I ,.~,.) I
1 .9llo)
(
(
0
O.Ollo)
(
(
0
1
1 • 9'-) ( 0.
1
g,.) I(
I
0
0. O'llo)
0
I
I
I
I
(
2
3.811,)
2
O.Ollo) o. 0'1.) ( 1 .9'1.) ( o.o,r,J I ( 3. B'l,J
I
1,1 1. 1 I IOUS SYNDROMES I 0
0,0'1,) (
1
I. 9'1,) (
0
o,o,.,
0 0 0
I
I 1
( 0.0'1.) ( 0.0'1,) ( 0. Oll,) I ( 1 . 9%)
,,U1PES LABJALIS, RECURRENT
I
0 I 0 0 0 0 1
( 0. 0'1.) ( 1. 9'1.) ( o .o,., I ( 0. O'llo). ( 0 . 0'1.) ( 0.0'1,) ( 1 . 9")
I
II c
,.10RV
I
I 0 0 I
I ( '
I. 9'1.) ( 0.0'1,) ( o .o ... ,
0
0.0'1,) I (
0
0.011.) (
0
0. 011,) II (
1
I . 9")
. ,.. RvNGITJS (SORE THROAT) II I 0 0 0
I
I 0 I 0 I I 1
, .lS~.ELETAL
I
·I
( 1 • 9'J.)
2
I O. O'llo)
0
( 0.01')
0
( O.O'J.)
0
I
II
( 0.0'1,)
0
I( 0. O'llo)
0
I
II
I <
II
I. 9'1.)
2
I ( 3.H) I ( o.nJ ( O.O'llo) ( o.o,i,J ( O.Oll,) I < o.o,i,) ( 3.8'1.)
0
0
1.11
N
0
Table 10 (cont.)
!,,IIOV 0880
·•~EAlMENT
l.l>T NUMl!JER CL217
DOSE 10 MCG
I TOTAL VACCINEES I 53 PATIENTS) - DOSE 1

1---------------------------------------------------------
I DAYS POST VACCINATION NUMBER
CLINICAL
COMPLA tNTS
1----------------------------------------------------------------------------
I O 1 2 I 3 I I 5 WITH
COMPLAINTS
4
·································••1••········ .......... ········••1••········ .......... ··············•~••··· ••••••••••

NECK PAIN II c 1
1,91')
0
c o.o'ilt>
0
< o .o">
II <
O
o.o,.>
I< O
o.o">
Ic 0
o.o'ilt>
I
1 , 9'K,)
I
~RM PAIN I ' II 0 0 0 0 0 1
I , .91') 0 . 0%) 0.0llo) 0.0llo) 0.0%) 0. 0%) ' . 9'11,)
G!U~~TIVE SVSTEM
I
I o
I
I 1 0 0 , 0 2
I o.o'ilt> I 1, 9ll,) 0.01') o. o,i, > 1,91') 0.0%) 3.8'K,)
I I
ABDOMINAL PAINS/CRAMPS I o I 1 0 0 0 0 1
o. Olio) I 0,0ll,)
1lt.USEA
I o
I
I
1.H)
o I
O.Ollo)
o 0
0.0%)
I I
0. Olio)
O I I
'.9%)
1
< o.o1') I c o. o,., I < o,o,., 0,0%) ( 1. 91') ( 0. O'-) ( 1. 9%)
· . .- .:· ttS WITH COMPLAINTS

----------1----------1----------
6 I 4 I 1
----------
1
----------
3
----------
0
---------- -----------
12
c 11.J'ilt> < 1.s,., I < 1.91') ( 5.71') ( O.Ol') ( 22 . 6'W.J
I
' . 9")
, , 1, , 11!> WITH NO COMPLAINTS

---------- ----------1---------- ----------
52
----------
50
----------
53
---------- -----------
41
47 49 52
( 88.7~) ( 92.5~) ( 98.1%) ( 98.I~) ( 94.3~) ( 100.0'lC.) ( 77. 4'W.)
1·1:1< ,,111:, WI TH NO OATA

----------
0
----------
o I ----------
o ----------
0
----------
0
----------
0
---------- -----------
0
I ( 0.0%) ( O,Ollo) I ( O.Ollo) 0.01') ( 0. 01') ( O.O'K,) ( O.OY.)
0
0
"'
-
IV
Table 10 (cont.)

0880
• ,li 1'>LP. CL217
10 MCG
--- ---------------------------------------------------------------------------------------------
- TOTAL VACCINEES ( 53 PATIENTS) - DOSE 2 I
----------------------------------------------------------------------------1
OAVS POST VACCINATION I NUMeER
CLINIC AL ----------------------------------------------------------------------------1 WITH
COMPLAINTS 0
••••••• ••••••••••••••••••••••• ••••• .......... I I I 2 I 3 41 I 5
·········· ········ ···1 ····· ····· ... ................. ··· ·······1··········
I COMPLAINTS
qE ACTION , LOCAL (INJECT , SITE) 2 o I o I o o 1 I 2
____ 3.e,c, 1 __ <_ . 0.0,c,1 -1- c __ o . o,c,1 _,_< __ 0.0,c,1 __ <__ o . o,c,> __ <__ 1 . 9 ,c, >_ ----------1-c __3 . e ,. , __
PAIN ON INJECTION 0
0. o,c, ) (
0
0. 0,C,)
I(
0. o,c, I I (
O IO
0 . o,c,) (
O
0. 011. ) (
1
I • 9 ,C, )
I 1
I ( 1 . 9'1, )
I I I
SORENESS 2 o I o I o o o I 2
3 , e ,c, 1 < o.o,c, ) I < 0 . 0,c,1 I c 0 . 0,c,1 c 0.011. J < 0 . 0%) I < J.e,c,1
SVSTf MIC ----------
1
----------1----------1----------
I I 1 I 2
----------
0
----------
0
----------1-----
I
------
2
1,9,c, 1 < 1,9,c, ) I < 1,9,c,J I < 3.e,c,) I c o.o,c,J < o . o,c,> I I 1 3.B ~ >
-------------------------------------------- --------------------------------------------------------------------------------
WHOLE BOOV/GENERAL I 1 I 1 I 0 0 I I
I. 9 ,c, ) I . 9,C,) I . 11,C,) 0.0,C, ) 0 . 0,C, )
I
( ( I . 9 Y. ) ( ( ( ( 1.9,.)
I
FATIGUE/WE AKNESS I I 0 0 0 0 0 I
I.HJ ( 0 . 0,C,) ( 0 . 0,C,) ( 0.0,C,) ( 0 . 0%) ( 0 , 0 ,C, ) ( 1 . 9'1, )
I
MAL AISE I 0 I 0 I 0 0 0 1
o.O'll. l I ( 1.H) ( o.o,r. ) I ( 0.0,C, ) ( 0.0,r. 1 ( 0 . 0,C,) ( I . 9Y.)
HEADACHE I 0
0.01!.) I
I (
I
I. 9 '11 ) (
1
, .9,C, )
I
I
I (
1
1 . 9,C,) (
0
o.~J (
0
0,0,C, ) (
I
1 . 9,C, )
I
MUSCULOSKELET AL I 0 0 I I I 0 0 2
0.0,C, ) ( 0.0,C, ) ( I .9" l I ( '.9,C, ), ( 0.011.) ( 0 . 0") ( 3 . 8,C, )
I
NECK STIFF NESS I 0 0 I I I I D 0 2
0.0" ) ( 0 . 011. > I ( 1 . 9"J I ( 1 . g" I ( 0 . 01!.) ( 0 , 0,C,) ( 3,8,.)
-----------------------------------,----------
PERSONS WITH COMPLAI NTS 2
----------
I
----------,----------
1 I 2
---------- ---------- ---------- I -----------
0 1 2
3.8"') ( I.HI ( I .9,C, ) I I ( 3 . B"l ( 0 . 011.) ( I . 9" J ( 3 . BY. I
-----------------------------------1---------- ---------- --- -------,---------- ---------- ---------- ----------1-----------
PERSONS WITH NO COMPLAINTS ' 51 52
( 96 . 2%)
52 I 51
( 98.l ,C, )
53 s2 I 5,
< 9e.1"1 I c 96.2"1 (100 . 0,C, ) ( 99 . 1" ) ( 96 . 2Y. J
0
0
~
rv
N
Table 10 (cont.)
PATIENl COUNl CLINICAL COMPLAINTS
I ,,
0880
, . ,11 :141
1,u;..1uER CL217
I, .... r 10 MCG
!--------------____ TOTAL_VACC::::sP:ST5:A:::::::::---DOSE_2 __________________ 1 NUMBER

CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------I
0 I I 2 I 3 4 I 5
WllH
I COMP I NT S
LA
••••••••••••••••••••••••••••••••••• •••••••••• ••••·• •••••l••••••••••I•••••••••• ••••••••••J•••••••••• ••• 0 ••••••f••••••••••
PERSONS WITH NO DATA
----------
0
----------1----------1----------
o I o I o
----------1----------
o I o
----------1-----------
o
o.o~l < 0.0~1 I < 0.0~1 I < 0.0~1 C 0.0~1 I < o.o~> I < 0.0~1
~
0
\JI
N
""
Table 10 tcont.)
•l . , 0880
"':.. • . v,t NT
I ·.' 1 NIJMBER CL217
f;\j ) [ 10 MCG
I TOTAL VACCINEl!:S ( 26 PAT! ENTS) - DOSE 3 I

l------------ -- --------------------------------------------------------------1
I DAVS POST VACCINATION I NUMBER
CLINICAL
COMPLAINTS
1--------------------------------
I O \ 1 I 2
---------------•---------------------------\
3 I <I I 5
WITH
COMPLAINTS
•••••••••••••••••••••••••••••••••••t••••••••••I••••••••••!•••••••••• ••••••••••l••••••••••I•••••••••• •••• 0 ••••• ••••••••••
-- ------------------·--------------1----------1----------1----------
PERSONS WITH COMPLAINTS I O I O I O
----------1----------1----------
O I O I O
---------- -----------
0
----------------------------1- c __ o.0%) -1- <__ 0 . 0%) -1-< __ o. □%> __ c __ o.0%>_!_< __ 0.0%> _1 _<__ o . □%> ___________ 1_1__ 0 . 0%>__
PERSONS WITH NO COMPLAINTS ( 17 17 \ 17 17 ( 17 1 17 ( \7
I 1100 . 0%} <100.0%> I c100.0%l 1100.0%> I c100.0%) I <100.0%> I c100.0%>
-----------------------------------1----------
l•ERSONS WITH NO DATA I O
----------1----------
O I O
----------1----------1----------
O I O I O
----------1I -----------
0
I c 0.0%) < o.O%l I c 0 . 0%) < o. □%l I < 0.0%) I < 0.0%> I I < o . □ %>
0
0
VI
1\1
"'
Table 11
PATIENT COi.MT Hl XIt1Ult TEHPERATUIIES
RECOMBINANT HEPATITis B VACCINE
STUDY I 0880
TIIElTHEHT
LOT H\Jtl8EII CLU7
DOSE : 10 HCG

1---------------------------------------------------------------------------------------I
I DAYS POST VACCIHATJOH I tUHMR
Hl X TEMPERATURE
IO!G f , ORlll
l---------------------------------------------------------------------------------------1
I O • 1 • 2 • 3 • IJ • S • •
WITH
• HlX TEHP
•••••••••••••••••••••••• •••••••••••••••••••••••••••••••••••••••••••••••••••••••!•••••••••••••••••••••••••••••••••••••••••••
I • I • I • • •
< '" I 31J • 38 • 33 I 35 I 35 I 33 • I 29
I I 89.5:o • UD0.0iO • I 86.81.J • I 92.17.1 • C 91J.6%1 • I 94.37.1 • • I 76.31.1
'19 - 99. 'ii •I " •I o •• it

•• 3 I• 2 II 2 •• I• e
I ( 10.s;o • ( O.0iO • I 10 . 51.1 • ( 7.97.I I ( 5.4%1 I I s.n, • I ( 21.lY.I
I I • • I I I I
100 - · 10D.'il • O • o • l I o • D I 0 • • l
• C o.or., • ( 0.01.1 • ( 2.67.) • ( 0.07.1 • ( D.07.1 I ( D.07.1 • • I 2.67.l
------------------------•----------•----------•----------•----------1----------1----------•---------------------•-----------
TEMPER ATURE TAKEN I 38 • 38 • 38 • 38 I 37 • 35 • • 38
• ( 71.TI.I . C 71.77.1 . C 71 . 7iO. ( 71.7lO. ( 69.87.J I ( 66 . 07.1. • I 71.7:!l
------------------------•----------1----------1
TEMPERATURE HOT TAKEN • 15 • 15 I----------•----------•----------•----------•---------------------•-----------
15 • 15 • 16 • 18 • • 15
• I 28.3?.> • I 28 . JiO • I 28.3iO • C 28 . 37.1 • I 30.2?.l I I 34.D7.l • I I 28.3?.l
0
~
\II
"'
\11
Table 11 (cont. )
RECOt1BINANT HEPAT1r1s 8 VACCitl'E
STUDY 0880
TRUTHENT
LOT NIJtlBER Cl217
DOSE 10 HCG
I TOTAL VACCINEES C Sl PATIENTSI - OOSE 2 I

1---------------------------------------------------------------------------------------•
• OAYS POST VACCINATION I NUl18ER
HAX TEHPERATURE
(OEGF,OAALI
1---------------------------------------------------------------------------------------•
I O I 1 • 2 I 3 I It I 5 • I
WITH
.11AX TEHP
•••••••••••••••••••••••••••••••••••l•••••••••• •••••••••••••••••••••••••••••••••I•••••••••• •••••••••••••••••••••• •••••••••••
• I • I I • I •
< 99 • 28 I 27 • 28 • n I 25 • 23 • I U
I I 87.5:0 I I e1 . 1:o • I 96.67.) I ( 96.lo7.I I I 1!9.37.1 I C 81!.SlO I I I · 71.97.I
• I I • • • I I
99 - 99. 9 I 4 I 1t I 1 I 1 I 3 I t I • 8
• t u . 57.1 I I 12.97.1 I t 3.47.1 • t 3.67.1 I C 10. 1:0 I c 7. 77.) I • C 25.0lO
I I • • I I I •
102 - 102. 9 I o I o • a • o I o I 1 • I 1
I t 11,07.1 I I 0.07.1 I C 0.07.1 • I 0 . 07.1 I I 0.0iO • I 3.&Xl I I c 3.17.1
------------------------l----------l----------l----------t----------l----------l----------1---------------------1-----------
tEHPERATURE t Al(EN I 12 I n I n I za I 2a I 26 I • 32
I I 60.47.1 I I 51!.57.l I c 54. no • I 52.&lO I I 52.87.1 I c 49 , lY.I • I t 60.ft,O
------------------------1I ----------1
tEHPERATURE HOT TAKEN U I
----------l----------l----------l--------·-1
22 I 24 I 25 • 25 I
-·--------l---------------------l-----------
27 • I 21
I C :59.67.1 I I 41.5XI I C ft5,l7.1 I t lt7.27.I I C lt7.2l0 I C 50.97.I I I t 39.f>XJ
0
0
lJ'I
N
0-
Table 11 (cont.)
PATIENT COUNT NAXIHU!t TEttPEAATURES
RECOtlBINAHT HEPATIT~S B VACCINE
STUDT D880
TREATt1ENT
LOT NU18ER Cl217
DOSE 10 ttCG

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATJON I NUt15U
NAX TENPERAnJRE 1---------------------------------------------------------------------------------------I WITH
(DEG F, . DRAlJ I O I 1 I 2 I 3 I 4 I 5 I I I NAX l[t1P
••••••••••••••••••••••••l••••••••-1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1•••••••••~1••••••••••
I I I I I I I I
< 99 I s I s I s I s I s I s I I s
I 1100.DX) I 1100.0X) I (100.0IJ I (100.0Z) I 1100.0XI I 1100.0X) I I 1100.07.1
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEttPERATURE TAKEN I 5 I 5 I s I s I 5 I 5 I I 5
I c 19.2lO I I 19.ZiO I I 19,211 I I 19.2;0 I I 19.2;0 I I 19.2;0 I I t 19.27.1
------------------------l----------l----------l----------l----------l----------1----------1---------------------1-----------
TEttPERATUl!E NOT TAKEN I n I u I u I 21 I 21 I 21 I I 21
I I 80.81) I I eo.&lO I I 80.611 I I 80.81) I C 80.811 I I eo.e;n I I I 80.87.)
0
0
1.11
N
-.!
Table 12
PATIENT COUHT CLINICAL COMPLAINTS
~Tut1·1 08B0
rHEfiTMENT
LOT NUMBER CL2t9
OOSE 10 MCG
--
------------------------------------------------------------------------------------------
TOTAL VACCIHEES ( 46 PATIENTS} - DOSE I
----------------------------------------------------------------------------
DAYS POST VACCINATION NUMBER
CLINICAL _ 1---------------------------------•------------------------------------------ COMPLAINTS
WITH
••••~~~:~:~~!!•••••••••••••••••••••1••••~•••••1••••!•••••1••••!•••••1••••~••••• •••• : ••••• ····~·-·••1••···••0•• ••••••••••
REACTION. LOCAL (INJECT. SITE} I 8 2 I O I O O 0
B
( 17. 4Y.)
----.. ,.--- -- ----------------------1-:-·::;::-1-:--::;::-1-:--::~:-1-:--::;::- -:--::~:-1-:--::;::-•---------- 2

4. 3,.)
~llRENESS I s
10.9"} 2 I 0 0 0 0 5
4. 3,.> I 0.0,.} 0.0%) 0.0") 0 . 0%) I 10. 9'11.)
I
"- ~H. NOS I 2.2%)
I o I o I o I o
c o.o,.> I < o.o,.> I c o.o,., I < o.o">
0
0 . 0,.)
II < 2. 2,.,
~;~~,c I I
2.2">
------,---1------2---1------2·--1------,--- ------0---,----------1------4----
( 2.2,.J I < 4.3,.> I < 4.3,.l I c 2.2%> 0.0"} I I < e.1%>
.. ---- ------------------------------------------------------------------------------------
·:. • : 1 !, l:lODV /GENERAL
--.wE.l TING
I
I
1
2. 2")
1
(
0
o.o,.J I
0
I
I
( o. :,.} I (
0
0.0,.)
0
(
o.:,.) I (
0
o.o,.>
0
(
1
2. 2,i,)
1
2.211,) ( o. 0'11) ( o. o'II > I ( 0.0%) ( O.O,r,) I < 0.0lO ( 2. 2,i,J
I
: ,,; • J RATORV I 0
0.0%) (
0 2 I 2
4. 3,.)
I D z
0.0'11) ( "· 3,.} I ( 2. 2'11) ( 0.0%} ( 4. 3'11.)
I
•:INUSITIS I 0 0 0 0
I
I
( 0.0%) ( 0.0,.) ( 0.0%} ( '
2.2"). ( o. me.) (
0
0 . 0'k) (
1
2.2%)
PH~RVNGITIS (SORE THROAT) I 0 0 I 0 0 0 I
I ( o.o,.> I ( 0.0,.) ( 2. 2,.) ( 0.0%) ( 0.0'11) ( 0.0%} ( 2. 2,i,}
t•i•PER RESPIRATORY INFECT'' NOS I

I
0
I
I 0
". ;,. , II 1 0
( o. o" > I ( 0.0,.) ( ( '
2. 2") ( 2. 2") ( 0 . 0,.)
2
4.3,.)
,II
(
I I
1,11; ,; ~TIVE SYSTEM . I
(
1
2 . 2,r,) I (
1
2.2%) (
0 I
0.0,.) I (
0
0.01')
I
I ( o.~,.1 I( 0
o. o,.,
I
I
I
I (
2
4. 31'}
0
0
\JI
rv
OIi
Table 12 (cont.)

5 TUVV 0880
TREATMENT
LO T NUMDER CL219
OOSE , 10 MCG

---------------------
CLINIC AL WITH
COMPLAINTS 0 I 2 3 4 5 COMPLAINTS
••••••••••••••••••••••••••••••••••• • ••••••• •• )•••••••••• l•••••••••• l •••••••••• l••••• ••••• l •••••••••• t•••o•••••• I•••••••• ••
DIIIRRHEA o II , 0 0 0 0 I
o.o,c, ) 2 . 2% ) 0.0%) 0. 0 ,C, ) 0.0%) 0, O,C, ) 2 , ZlC. )
NAUSEA 1
2. 2% )
IO
( 0 •o,c, J ( O. Oo,c,) II (
0 . OY. J
O
(
O
0 . OY. J (
O
0 . OY.)
I 1
C 2 . 2'- l
!i:~11 TING o , o Io o o ,
0.0,c, 1 c 2.2,c,) < o.oY. J I < o.oY. J < o.o,c, J < o. o'- > c 2. 2,c, 1
·, ·,,;·1 s rll TH COMPL AINTS
----------
9
----------
3
----------1------
'2
----
2
----------
I
----------
O
---------- -----------
10
( 17 . 4 %) ( 8,SY. ) ( 4.3 %) ( 4. 3%) ( 2. 2%) ( 0.0%) ( 21 . 7 ,C, J
1 ·, ·,11$ ~J ITH NO COMPL AINTS

----------
38
----------
43
----------
44
----------
44
----------
45
----------
46
---------- -----------
36
_<_82.:,C, J -1-(-93,:,C,) - _<_95 , : Y. ) -1-(-95.:Y. ) - _<_97.:,.) -!-(100 .: ,C, )_ - - - - - - ----,-(-78 . : %) --
, . •~ IN!> WI TH NO DATA
1 c 0. 0,c, 1 < o.o,c, ) I C o.o,. J I C o.o,. J I C o.o,. J I c o.oY. ) I I C o . o,c,J
0
0
V,
"'
-0
Table 12 (cont. )
STUOV 0880
TREATMENT
LOT HUMBER CL2l9
DOSE 10 MCG

---------------------
f.LINICAL WITH
COMPL-.IHTS 0 I I I 2 I 3 I I 5 4 COMPLAINTS
··································· ········••1••······••1••········ .......... ··········1·········· •••••••••• ••••••••••
~E-~TJOH,_LOCAL-(IHJECT._s,TE) _____ j_ <__ &.~'I.) _1_c __ 2.!,., _j_< __ o_g,.) _j_c __ o,g,., - _< __ o_g,.,_,_< __ o_g,., - 4
8.7'1.)
; l,FlAMMATION 31 o I o I
I (
o
I (
o I
I (
o
I I 3
6.5%) ( 0.0'1.) ( 0.0'1,) 0,0'1.) 0.0'1.) 0.0%) I 6. 5'11,)
I
1 I
____ o_g,.> _I_ <__ 2.~"' __ c__ o_g,., _1_ <__ o_g,.,_1_ <__ o_g,., _l_< __ o.g,., _
. .- I•:' 5S
I c 2. 2"1
----------1-----------
··:s ~ITH COMPLAINTS 3
6,5'1,)
1
2.2'")
o
0,0'1,)
I (
o
0.0'1,)
0
0.0'1.)
0
0 .0'1.)
1
I c
4
e . 11,J
- :, , ,; \ofl7M NO COMPLAINTS ----------1----------
43 45
----------
46
----------
46
----------
46
----------
46
----------1-----------
42
( 93.5'1,) ( 97.8") ( 100. O'I.) ( 100.0'1,) ( 100.0") (100.0") I ( 9 l • 3'1.)
.:m:; WITH HO DATA
----------1----------
0 0
----------
0
----------
0
----------
0
----------
0
----------1-----------
( 0,0'1.) ( 0.0'1.) ( 0.0'1.) ( 0,0'1.) ( 0 , 0") C O. O"-l 1 < o_g,.,
0
0
"'
....,
0
Table 12 (cont.)
STODV I 0880
TREATMENT
LOT NUMBER CL219
OOSE 10 MCG

---------------------
OAVS POST VACCINATION NUl\l8ER
CLINICAL WITH
CO!olPLAINTS 0 2 3 4 5 COMPLAINTS
•••~•••••••••••••••••••••••••••••••l••••••••••l••• ••••••• l••••••••••l••••••••••l••••••••••l••••••••••l••••••••• • I••••••••••
r,~r.TlON, LOCAL (INJECT. SITE) I O
0,0,.)
I (
I
5.9")
0
o,o,., (
I o
a
0.0%) ( 0.0%)
0
o.o,.,
II I 5. 9,.l
I1 ----------1---------- ----------1----------1-----------
( o.o,., I ( o.o,.,
. .. Ill 0 0 0 o 0 I I ,
o.o,., I c 5.9"> o,o,., < o.o,., I I c 5 . 9,.l
·· -w1c -------------------------,------,---1------,--- ----------1----------
I ----------,----------1-----------
I ( 5.9") I( S . 9")
I
5.9,.)
1 I
5,9,.l I < s.9,.l
1
< 5.9,.l I
I I
I c 5.9Y.J
I ,
~,' ' !:K[1V/GENERAL
s.~,., I I
5.H)
I
5.9,.)
1
5.9,.)
1
5 .9,.) 5 . 91')
1
5.9,.)
I
I ,
11(:;.t••CHE
( 5.9,.l I (
1
S.9") (
I
5.9%) ( I( 1
5.9") 5.9%) 5.9,.)
I
5.9Y.)
·- -----------------------------1----------
•·· 1:-1")NS WITH COMPLAINTS I 1 ----------
2
---------- ---------- I----------
1 1 1
, 2
( 5.9") ( 11.8") ( 5.9,.) ( 5.9") ( 5.9") 5. 9%) ( I I . 8,.)
·· ·------------------------------1----------
.;.-.. •us I
---------- ---------- I
---------- ---------- 16
---·------1-----------
1 15
wtTH NO COMPLAINTS 16 15 16 16 1&
I 94_1,., I c ee.2"> 1 94.,,., I c 94.1"1 I 94.1,., ( 94,1") I c ee. 2,. >
-- - · - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
••r 1: .-,. •II~ WITH NO DATA
1
----------1----------1----------1----------
0 I O I O I D
----------
0 0
----------1 ------0----
0.0") I ( O.OT.) I ( o.o,., I ( 0.0") ( o . o,., o,o,., 1 ( 0.01')
,:,
0
....,
""
...
Table 13
PATIENT COUNT NAXIHUl1 TEHPERATURES
RECONSIHANT KEPATI~lS 8 VACCINE
STUOY 088(1
TREATMENT
LOT N..ltl:IER Cl219
DOSE 10 11CG
I TOTAL VACCINEES I 46 PATIENTS) - DOSE l I

1---------------------------------------------------------------------------------------I
I DA'YS POST VACCINATION • IM18ER
HAX TEHPERATURE
IDEG F, ORAll
1---------------------------------------------------------------------------------------I
I O I 1 • 2 I 3 • 4 I 5 • •
WITH
• MAX TEMP
••••••••••••••••••••••••••••••••••• l••••••••••••••••••••••••••••••••••••••••••• I•••••••••••••••••••••••••••••••• •••••••••••
I I I I I • I •
< 99 I n I 35 I 34 I 31 I 54 I 33 I I 26
I 1 86.87.1 I 1 94.6lO I I n.,r.1 I 1 86 . tr.1 I t n.,r., I 1 '7 . 1r., I • 1 68.4r.,
I I I I I I I I
99 - 99.9 I s I 2 I 3 I s I 3 I l I I 12
I I n.2x1 I I s.47.J I 1 8.1r.1 I t 13.9"/.I I t 8.1x1 I c z.,r., I I 1 31.6?.>
------------------------1----------1----------I----------I---------- I----------I----------I---------------------I-----------
TEHPERATURE TAKEN I 38 • 37 I 37 I 36 I 31 I 34 I I 38
I I 82.67.1 I I 80.4l0 I < 80.47.1 I t 78.~I I I 80.47.1 1 t 73.91.1 I I 1 82.6i0
------------------------1----------1----------l----------l----------l----------l----------l---------------------•-----------
TENPERATURE NOT TAKEH I 8 I 9 I 9 I 10 I 9 I 12 I I 8
I t 17 . 47.1 I t 1'1,6:1.1 I I 19.67.1 I t 21.77.1 I 1 19.6?.I Ic 26 . 1:0 I I 1 17.47.I
0
0
\11
""'
1\/
Table 13 (cont.)
PATIENT COUNT HAXIH\Jt1 TENPEl!ATIJRES
,u:cotmINlNT HEPATITIS 8 VACCUIE
STIJOT 0880
Tl!UTHENT
LOT NUl1BEI! Cl219
OOSE 10 t1CG
I TOTAL VACCIHEES ( 46 PATIEHTSI - OOSE 2 I

l---------------------------------------------------------------------------------------1
I OAYS POST VACCINATION I NUMBER
HAX TEHPEl!ATUl!E
IOEG F, OOAll
l---------------------------------------------------------------------------------------1
I O I 1 I 2 I 3 I It I 5 I I I NAXWITH
TEHP
••••••••••••••••••••••••l••••••••••l••••••••••l•••••••-•l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 I a I 24 I u I tS I n I to I I 11
I c es.s:o I c u.3Y.I I c eo.ex, I c 96.ZY.I I I n.1x1 I c s1.oio I I 1 6S.4:o
I I I I I I I I
99 - 99. 9 I 3 I 2 I s I 1 I 7 I 3 I I 9
I I 11.SY.I I I 7.7Y.I I I 19.2,O I I l.87.l I I 26.97.1 I I ll.0lO I I I 34.67.l
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEltPEIIATURE TAKEN I 26 I 26 I 26 I 26 I 26 I Zl I I Z6
I I 56 • .5Y.I I I S6.5Y.l I I 56.SY.I I I 56.57.1 I I 56.57.1 I I S0.0Y.l I I I 56.51.J
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TErtPEIIATURE HOT TAKEN I 20 I 20 I 20 I 20 I U I 23 I I zo
I c 43.s:o I c u.sr., I c 1tJ.s:1.1 I I ttJ.s1.1 I c 4l.sx, I t so.ox, I I 1 43 .sio
c:,
0
Ill
""'
""'
Table 13 (cont. )
PATIEHT COUNT HAXIt1Ul1 TEHPERATURES
RECOt18INANT HEPATITIS 8 VACCINE
STUDY , oeso
TREATtlENT
lOT tul8£R : Cl219
DOSE 10 HCG
• TOTAL VACCINEES I 21 PATIEHTSl • DOSE 3 I

l---------------------------------------------------------------------------------------1
• DAYS POST VACCIHATIOH I HUMBER
•-------•---•••·------------------------------------------------------------------------1
11AX TEMPERATURE
«DEG r, OR AU I o
................................... I 1
, ,
.......... I..........•..........
2 I 3 I 4
, ,
.......... I..........•..........•..........
s I I • 11• WITH
x TEMP
•..........
< 99
•I 10
•I e II 9
•I 10
II ci
II , •I •I 7
• 1 e3.3;0 I, 12.no • 1 e1.ex, I I cio.9;0 I , e1 . ex1 I, e1.er., I •, ss . 3;0
• I I I I I I I
99 - 99. 9 • 2 • J • 2 I l I 2 • 2 I • s
• I 16.1lil I l 27.JiO • t 1e.2;0 I r 9.17.1 I t 1e . 2x1 I t 1e . 2;0 I I l 41.71/.l
------------------------ •----------•----------I ----------I----------I----------I----------I---------------------I-----------
TEt1PERATIJRE TAKEN I 12 I 11 • 11 I 11 I 11 I 11 I I 12
I l 57.lXJ I ( 52.4XI • l s2 . 1t:o • I 52.ltX) f I 52.4:1.1 I I 52 . 4XJ • • I 57.liO
------------------------•----------•----------•----------•----------1----------1----------•---------------------•-----------
TEHPERATURE NOT TAl< EH • 9 I 10 • 10 I 10 I 10 I 10 I I 9
• I 42.9:1.1 I l lt7.6:t.l I I 4 7 . 6Y.I I I 47.61.l I I 47.6l0 I I 47.67.1 • I I 42.97.l
0
0
u,
~
.co
Table 14
PATIEHT COUNT CLIHICAL COMPLAINTS
STUDV 0880
TRl:ATMEHT
LOI NUlllltER CL220
OOSE 1 10 IIICG
I TOTAL VACCINEES ( 43 PATIEHTS) - OOSE I

----------------------------------------------------------------------------
0AVS POST VACCINATION NUMIIER
LLINICAL 1---------------------------------------------------------------------------- WITH
..... , ...............•.•.•....•..... ·········· ........................................ ··········1··········
lOMPLAIHTS 0 I 2 3 A 5 COMPLAINTS
••••••••••
· ·1 ~IC 0 3 0 0 0 0 3
0 . 0'1) ( 7.0'1) ( 0.0%) ( 0.0'1) ( 0.0'1) ( 0.0'1) 7.0'1)
~ Fl'. .' 0~ iuEHERAL 0

0. 01')
3
7,0'1) (
0
0. 01') (
0
0.0'1) ( o _g,,,, I( 0
0 . 0,r,1
I
I (
3
7,011)
• ·. , ,,;ue,wEAKNESS 0 2 0 0 0 0 2
O . O'll,) 4,7'1) ( 0.0%) ( O.O'll,) ( 0.01') ( 0. 0'I) ( 4 . 7Y,)
11t. 'lJACHE
I ( o.~,.,
I
I 0 0 0 0 1
2. 3'1) ( o. 0'1) ( o.o,i.J ( 0.01') ( 0 . 0'1) ( 2, 3,.)
. NS
---- -------------------------1----------
WITH COMPLAINTS 0
----------
3
----------
0
----------
0
----------
0
----------
0
---------- -----------
3
( 0 . O'll, ) 1.0'1) ( 0.0%) ( 0. O'I) ( 0.0'1) ( 0.0'1) ( 7.0'4)
., ... r,s WI TH NO COMPLAINTS 43

----------
40 ----------
43 ----------
43
----------
43
----------
43
---------- -----------
◄O
(100.010 <100.o,c.> I (100.0 ... , (100.0'll ) ( 93.0'1)
I
( 93.o•> ( 100 . 0 • >
---------- ----------1---------- ---------- ----------,---------- -----------
;·,11•, WITH NO DATA
(
0
0.01') (
0
o.o,., 0
(
I
o.o,c.>
0
I <
0
0.0'11,) ( 0.0'11,) ( o.~.. , I
0
( 0.0'4)
0
0
\JI
1.,1
"'
Table 14 (cont.)
. ,,.,.,, 0880
• 1. I ' I lt.!(HT
• , , r ,.UMBEP r CL220
· ,· , .,\: 1 10 MCG
, t l~ICAL
• . m-'U'1NTS O I 2
TOTAL VACCIHEES (
OAVS POST VACCINATION
3 4 S
43 PATIENTS) - DOSE 2
-------------------------------------------------------------------- --------
HU~OEP
WITH
COMPLAINTS
I
' •·•••••••••••••••••••••••••••••• •••••••••• •••••••••• •••••••••• •••••••••• ••••••••••'••••••••••'••o••••••• ••••••••••
•. ION, LOCAL (INJECT. SITE)
(
4
9.3'1) l
3
1,011,) (
1
2 .3Y.) , __ <__ D.OY.)
_< __ 2,3'1) I
o __ <__ O.O'I)
o _
I
I (
"
9. 3,t,)
V~IH---------------•----••-•---,-----•,--- ----------
2,3'1)
I
----------
(
I
2.3'1) ( 2. 3'1) (
I
2.3'1) I( I O
0.0'1) l
0
0.0'1)
---------- -----------
(
1
2. 3'1)
SORENESS I '2
4.7l" (
1
2.3'1)
0
( o. 01') ( 0.0S)
o
(
o
0.0Y.) II ( o
0.0SJ (
2
4.7'1)
IN0URATI0N 0 0 0 I
( '
2. 3'1) ( 0. 0Y.) l 0.0Y.l ( 0.0S) (
0
0. 0,C,) (
0
0.011,) ( '
2. 31')
HEMAT0MA 0 I 0 0
( 0.011,) ( 2.3'1) (
0
0.0Y.) ( 0.011,J ( 0.0'11.) (
0
0. DY.) ( '
2.3'1)
·---------------------------------- ----------
5VSTEMIC 0
----------
2
----------
2
----------
'2
----------
0
----------
0
---------- -----------
2
0. 011,) ( 4. 7") ( 4,711,) ( 4.7'1) ( 0.0Y.J ( 0. 0Y.) ( 4. 711,)
•·,••:>, f eoov /GENERAL I 0

0. 011,)
I
2,311,)
I
,
2. 311,)
1
,311,)
0
0.011,)
I
o.g,., I 1
2. 311,)
II
( ( { 2 ( ( (
·I
•:lA0ACHE
.1·1,lAT0RV
I
I
0
0.0'11,)
0
0. 011,)
l
(
I
2 ·:,.,
2,3'1)
I,
I
(
1
2. 311,)
'
2. 3'1)
(
(
1
2 .3'11.)
2 .~'II.) . I,
(
0
0.(111,,
o.~11,)
{
(
0
0. 011,)
0
0. 011,)
I
(
(
'
2,311,)
'
2.311,)
uPrER AESPJAAT0AV INFECT •• NOS II ( o

I I
I c 2. 3SJ
-----------------------------------1----------
0,0'IJ
---------- ----------
1
2. 3'1)
----------
(
--------·-
1
2. 3Y.)
----------
(
1
2. 3Y.) I (
0
0.011,) (
0
0. UY.) '
rEAS0HS WITH COMPLAINTS 4 5 3 3 0 0 ----------1-(-14.~11,)--
I c o. 311,1 ( I I .6'1) ( 7.011,) ( 7.0'1) ( 0.011,) ( 0 .011,)
-----------------------------------1----------
PEAS0NS WITH HO COMPLAINTS ,I 39 ---------- ----------
40
---------- ----------
43
----------
43
---------~,-----------
37
38
I < 90. 7Y.l
40
Bll .4'1) ( 03.011,) ( 93.0'1) ( 100.010 (100.011,) I( 116.011,)
0
0
1.11
VI
0-
er
..
V\ •
z . .
wx- •
:::, •
z
-
ID~ C •
~ -' .
Q. ..
2 •
cc
C
0 •
u •
..• I
. I
I
...
I
I
t
I
'
..••• .
I
'
I
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I
I co
'
I .,, ..• 0
N
"'"'
I
I
t
I
.•
.
I
g I'
I
•••
' I • 00
."' ... z
0 "" .•• C
."'-
%
C
---
.....
%
V\
,-
zz
C
Q.
..,
u
u
co
.
• .
C
cu
> .., 0
..JU
Q. C
> "' 0
. ..,.,.
lli
0 Q.
...• .
UIII Ill
.µ
....
..... "'
.., I
Ill
>
..,.
--
~ ....:z ..
% I
UI
u,
I Q
.. I
>•t
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N e
...• 0
00
.
..J Q.
...
UIII
,-4 :r ..J
j
z ..
:i z
cc
u :z
0 I
I
I
•••
• 00
.
,- ID '' -·..• 0
. ..,
Zlli I
WO
-u
I
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. -
,-
I .
C a:
Q. I
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I C •
.••• CJ~
-
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I
•
••• ....
I
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...•
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OU
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..
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•• 0C
a, .JO
0 u-
.."' .
..J
c-
:z
0
z
l:
_..,
U C
:s
:: :,.
~! ' "'r
~
"'
Table 14 (cont.)
PATIENT COUNT CLINIC AL COMPLAINTS
'-tl tl\,,V I 0880
11, l' A'' I.IF.:IIT I
I •; , tl\lldUER 1 Cl220
:· ,~.·ir-: 10 MCG
I
I
TOT AL VACCINEES ( 38 PATIENTS) - DOSE 3
----------------------------------------------------------------------
OAVS POST VACCIN ATION
------ NUMBER
. INIC AL 1---------------------------------------------------------------------------- WITH
: ,~PL AINTS
•••••••••• I••••••••••
o 1 I••••••••••
2 I••••••••••
3 I••• •••••••
~ I 5
l•••••• •••• II••••••••••
COMPLAINTS
••••••••••
~- -~·······························
Me ALf l UN. LOC AL (INJECT. SITE) 0 2 2 0 0 0 2
O.O'll. ) 6.71, ) 6. 7'll. ) O.O'll ) 0. O'll, ) O. O'll. J 6. 7'11,)
SORENESS o 2 2 o o o I 2
O. O'll l ( 8 . 7'll. ) ( 6.7'll. ) ( O. O'll. ) ( O.O'll. ) ( O.O'll. J I ( 6 , 7'll. l
--···-----------------------------1----------
.,, , lEMIC I
----------
0
----------
0
----------
0
----------
0
----------
0
----------1-----------
I I
3.3'll. ) ( O.O'll. ) ( O.O'll.) ( O.O'll. ) ( D.O'll. ) ( O. O'll. ) ( 3.JY. )
·---------------------------------------------------------------------------------------------------------------------
II I II < o_g,., I II
, ;•tlll. E BODV /GENERAL
'1o\LA I SE
I.
. (
I
3 . 31, J
I
3 . J 'll. )
<
0
0.01, J <
O
o . o,r,J
O
< 0.0,r.1
_< __ o_g,.l_,_< __ o.g,.,_ll_< __ o.~,., -l-< __ o_g,.,_

o
o.o... ,
o_g,., I
1 1
J. 3 ,. )
1
3. 3")
11', r,/ ITH COMPL AINTS I 2 2 0 0 0 3
I
3 . 3'll. J ( 8.7,r. ) . ( e . 1 1, ) < o.o,r. J I ( 0.01, ) o.o,. , ( 10.0'll.)
u ·, WITH NO COMPLAINTS
29 21 I (100.os30 J _
_,_vs.1• 1_ I_<_v3.3,. l __ <_93 . 3" >__ 28
30
( 100.0,r. )
30
(IOO.o,r. )
--------
27
( 90 . 0,r.)
••· ·· 111 JH NO DAT A o o o I o 0 0 0

l o.o• > 1( o.o• > I < o . os i I < o . o• > 0.01. ) 0 . 0 '1 } 0 . OY. )
0
0
\It
ul
0,
Table 15
PATIENT COUNT HAXI111J11 TEMPERATURES
ST\JbY t 0880
TREATHEHT
LOT HUtlBER : CL22O
DOSE 10 tlCG
I TOTAL YACCIHEES C 43 PATIEHTS) - DOSE 1 I

1I ---------------------------------------------------------------------------------------I
DAYS POST VACCINATION I HUMBER
MAX TEMPERATURE
I DEG F, ORAL I
1---------------------------------------------------------------------------------------I
I O I 1 I Z I 3 I 4 I 5 I I I MAWITH
X TEHP
••••••••••••••••••••••••l••••••••••l•••••••••• l•••••••••• l•••••••••••••••••••••l••••••••••l•••••••••• l•••••••••u l••••••••••
I I I I I I I I
< 99 I 36 I 40 I 39 I 39 I 36 I 32 I I 31
I c es.r.1., I c 9s.2x1 I c 95.ox, I c 9s.o:o I 1 94.n, I noo.ox, I I c n.e:o
I I I I I I I I
99 - 9-,. 9 I 6 I 2 I 2 I z I z I o t I u
I C14.3%1 I I 4.9i0 I C s.o;o I C 5.0iO I I 5.3r.l I C 0.0iO I I C26.2%1
------------------------l----------l----------l----------l----------
TEMPERATUl!E TAKEN I 42 I 42 I 40 I 40 l----------1----------1---------------------I-----------
• 38 I 32 I I 42
IC 97.T/.) IC 97.7%1 IC 93.0%) IC ,,.or., I Ce&.4i0 IC 74.4%) I IC ,1.n,
------------------------1----------1----------I----------I---------- I----------I----------I---------------------I ------ -----
TEHPER ATUl!E NOT TAKEN I 1 I l I 3 I 3 I 5 I 11 I I l
I I 2.3X I I I 2.3i0 I C 7.o:o I I 7.DiO I I ll .6Y.I I C 25.6Y.J I I I 2.31/.l
0
0
Vt
va
,0
Table 15 (cont.)
PATIENT coum lhx::t11JM TElfPEl!ATURES
RECOl1BIHANT HEPATITIS 8 VACCINE
STUDY 0880
TREATMENT
LDT NUlfBER Cl2ZO
DOSE 10 t1CG
• TOTAL VACCINEES ( 43 PATIENTS! - DOSE 2 I

1---------------------------------------------------------------------------------------•
• DAYS POST VACCllfATIDH • t«Jt18ER
11AX TEMPERATURE
I DEG F • Ol!AU • 0 •
, l I 2
, • 3 • 4 • 5 I
, •
,
•---------------------------------------------------------------------------------------• WITH
• MAX TElfP
........................•.......... ........... ..........•..........•.......... .•........ ..........•..........•..........
•• I I • • • I •I
< 99 37 I 36 I 37 I le • '37 I 33 • :n
• I 92. 51.) • ( 90. Ol I I ( 94. 9'/. I • I 97. 4l I • I 94. 9iO • ( 94. 31.1 I I ( 77. 57.1
• I I I I I I I
99 - 99. 9 • l I 4 I 2 I l • 2 I 2 I • 9
• I 7.s;o • ( 10.0;0 I I S.17.1 • C 2.67.) • I 5.llO • I 5.77.1 I • I 22.57.1
------------------------•----------•----------l----------•----------•----------•----------•---------------------t-----------
TEt1PERATUlE TAKEN I 40 • 40 I 39 I 39 • 39 • 35 I • 40
• I 93.0lO. I 93.07.1 I I 90.77.1 I I 90.77.1. ( 90.7iO I ( 81.47.1 I • C 93 . o;o
------------------------•----------•----------l----------l----------•----------•----------l---------------------•-----------
TEl1PERATURE NOT TAKEN • l • l .I 4 I 4 • 4 • 8 • I 3
• I 7. 01. J • 1 7. 07.1 I 1 9. 3;0 I 1 9. 37. I I I 9. lY. 1 • I 1a. 67.1 I I 1 7. r •
0
0
I.II
.c:,
0
Table 15 (cont.)
PATIENT COUHT MAXll1UH TEMPERATURES
REC0118INAHT HEPATITIS 8 VACCIIIE
STUDY OMO
TREATMENT
LOT NIJl1BEII Cl220
DOSE 10 HCG
I TOTAL VACClNEES ( 38 PATIENTS! - DOSE 3 I

Il---------------------------------------------------------------------------------------1
DAYS POST VACCINATI<»f I NU118ER
MAX TEMPERATURE
(D[GP',DRALJ
1---------------------------------------------------------------------------------------
IO I l I 2 I l I 4 I 5 I I
IIMAXTEHP
WITH
•••••••••••••••••••••••• l•••••••••• l••••••••••l••••••••••l•••••••••• l••••••••••l••••••••••l•••••••••• l••••••••••I••••••••••

I I I I I I I I
< 99 I 17 I 19 I 1a I 19 I 18 I 16 I I 16
I I es . or., I 1 95.07.J I ( 9o.o;o I ( 95.0in I 1 94.7XJ I 1 ~.i;o I I I eo.0%1
I I I I I I I I
99 - 99 . 9 I 3 I 1 I z I 1 I 1 I 1 I I 4
I I 15.0)0 I I 5.o;o I ( 10.0;0 I ( 5.0%) I ( 5.3)0 I ( 5 . 9%l I I ( 20.0;0
------------------------1----------1. --------- I----------I----------I----------I----------I---------------------I-----------
TEl1PERATURE TAKEN I 20 I 20 I zo I 20 I 19 I 17 I I 20
I I 52.6%1 I I 52.6:1.l I l 52 . 6%) I ( 52.6%l I I 50.0%) I ( IJ4. 7)(1 I I I 52.6%1
------------------------1----------1----------1----------1----------1----------1----------1---------------------1-----------
TEl1PERATURE NOT TAkEK I 18 I 18 I 18 I 18 I 19 I 21 I I 18
I I 47,4;0 I I 47.4:1.l I l tt7.";o I l tt7.4XI I I 50.0XJ I I 55.37.J I I I 47 . 4%1
0
0
VI
..,,. -
b
STUDY 882
00542
PROGRAM: Alum-Adsorbed Recombinant Hepatitis 8 Vaccine.

Study 882
PURPOSE: To evaluate antibody and clinical responses to 10 mcg

doses of recombinant hepatitis B vaccine 1n healthy
adult male volunteers.
VACCINE: Recombinant Hepatitis B Vaccine - Alum Adsorbed:

Lot #81990D/18066/C-L215
PRIMARY Shiro Iino. M.D.

INVESTIGATOR: First Department of Internal Medicine
Faculty of Nedicine
University of Tokyo
Hongo. Bunlcyo-ku. Tokyo
Tokyo. Japan
STUDY LOCATION: Tokyo and Osaka. Japan
STUDY POPULATION: The population consists of 40 healthy adults (20 to 59

years of age) who are negative for hepatitis B virus
serologtc markers. have normal liver function tests
and have not previously received any hepatitis B
vaccine.
STUDY PROCEDURE: Each participant receives a 10 mcg intramuscular

injection of vaccine on day 0, 1 and 6 months. Study
subjects are asked to record their temperatures and
any local or systemk complaints for five days after
each injection.
Serum samples are obtained prior to vaccination, and
at 1, 2, 3, 4, 5, 6, 7, 9 and 12 months post initial
injection. All specimens are assayed for HBsAg,
ant i-HBs, ant i-HBc 11nd severa 1 other laboratory
examinations by the bffij SantDles may
also be assayed at (b) (4) for
yeast antibody.
23961/861/1
1/19/86
00543
Study 882
RESULTS: INITIALLY SERONEGATIVE HEALTHY ADULTS

10 mcg lot #819900/l8066/C-L2l5 at 0, l, and 6 months
Injection Number
Dose Level _l_ .J_ _3_
10 mcg 40 40 40
When the cutoff was S/N >2. 1 , the ant i-HBs
seroconversion rate was 33%- (13/40) one month
after the first injection, and l0OS (40/40) at 7
1110nths. Table l lists antibody responses for up
to nine 1110nths of follow-up.
3. Clinical Coroplaints:
participants following each injection.
Type of Dose F ·------ in \ bY Inil!ction No.

CGID1•int ~ 1 2 3
Injection 10 ,neg 10 (4140) 13 (5/40) 10 (4/40)

Site
Systan\c 10 n::g 8 (3/40) 3 (1/40) 5 (2/40)
There have been serious or alarming adverse reactions

attributable to vaccine reported.
23961/861/2
l/19/86
00544
Study 882
Table 1
Antibody Responses Among Healthy Male Adults Following

Vaccination with 10 mcg Doses of Recombinant Vaccine
Lot C-L215 at 0, 1, and 6 Months
RIA
Cut-Off Anti-HBs Res2onse
Index Before 1 Mo. 2 Mos. 3 Mos. 4 Mos. 5 Mos. 6 Mos, 7 Mos. 9 Mos.
<2.1 40 27 12 8 4 4 4
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ------
2. 1-21 12 23 24 24 18 20 5 5
21-103 1 5 8 9 13 13 3 3
105-208 3 4 3 24 19
210- 1 8 12
Seroconversion % 32.5 70.0 80.0 90.0 90.0 90.0 100 100
23961/861/3
1/3/86
STUDY 883
OOSQS

Study 883

personnel II/ho are negative for hepatitis B virus
serologic markers.

Lot 81954I/1807l/C-L220 (10 mcg HBsAg/ml)
PRIMARY Stanley Plotkin, ~.D./Stuart Starr, M.D.

SECONDARY Vernon Brightman, DMD, DOS

INVESTIGATOR: Univ. of Pennsylvania
School of Dental Medicine
STUDY LOCATION: University of Pennsylvania

School of Dental Medicine
4001 Spruce Street
DATE STUDY INITIATED: November 13, 1984

healthy dental students of either sex (excluding
pregnant women), who are negative for HBsAg, anti-HBc
and ant 1-HBs, have a nonna 1 ALT 1eve l and have not
previously received any hepatitis B vaccine.
23981/1
l /16/86
OOSQb
Study 883

HBsAg) or 0.5 ml (10 mcg HBsAg) intramuscular
injection of vaccine at 0, 1, and 6 months. Vaccine
recipients record their temperature and any local or
systemic complaints for five days after each injection
of vaccine.
A blood sample 1s obtained approximately two weeks
before the first injection of vaccine. Post-
vaccination blood samples are obtained at 2 weeks, l,
2, 3, 6, 8, 12 and 24 months.
A11 serum samples are assayed for HBsAg, ant 1-HBc,
anti-HBs, and ALT. Samples may be tested for yeast
antibody. In addition. samples with an anti-HBs titer
> 25 mIU/ml may be tested for anti-a and anti-d
subtype spec1f1city. - -

5 mcg Lot Bl9541/18071/C-L220 at 0, 1, and 6 months
10 mcg Lot 819541/18071/C-L220 at 0, l, and 6 months
Injection No.
Dose (mcg) _l_ __2_
5 25 25 24
10 28 28 27
Serolog1c data at 7-8 months are available for 20
study participants who received a 5 mcg dose and
24 participants who received a 10 mcg dose of
vaccine.
23981/2
l /16/86
OOSQ7
Study 883
RESULTS: (Cont.) At 7-B months, ant1-H8s responses are as follows:
!. Anti-His PosHlve Gl'1T C11IU/111)

Dose All Responders
(lllCg) S/11 ?:2- 1 mIU/111 ?:10 Vaccinees S/t:l ?2. I IIIU/al ~10
5 100(20/20) 95(19/20) 215 . 3 215,3 259.0

10 100(24/24) 96(23/24) 81li3.2 863 .2 1084.9
3. C11n1cal Results:
Clinical follow-up data are available for 25 (5 mcg
dose) and 28 (10 mcg . dose) study participants
following the first two injections and for 23 (5
mcg dose) and 27 (10 mcg dose) participants
following the third injection of vaccine. Clinical
complaints and maximum temperatures reported
following each injection are provided in Tables
2-5. In sunmary:
Clinical Dose I Freguenc~ b~ Injection No.

Complaint .tmw. l 2 3
Injection 5 4(1 /25) 0(0/2S) 4(1/23)

S1te 10 7(2/28) 4(1/28) 4(1/27)
System1c 5 28(7/25) 4(1/25) 13(3/23)

10 29(8/28) 18( 5/28) 15(4/27)

ALT E1evati ons
Alanine a11inotransferase levels were normal in all
vaccine recipients except for elevations at 8
months in two participants. Case Nos. bJ (6
had ALT levels of 116 and 122, respectivel'-y~,--a-t•-
8 months. However, the serum sample obtained from
Case No. (b) (6) was hemolyzed. Subsequent serum
samples have not been obtained from this individual.
23981/3
1 /16/86
oosqa
. Study 883
ALT Elevations (Contd)

Case No J b) (G) had a noma 1 ALT 1eve 1 at 12 months.
Neither individual has sho"1TI any clinical or
serologic signs (HBsAg or anti-HBc) of hepatitis B.
HBV ~arkers (HBsAg)
One 1n1tially seronegative vaccine recipient (5
mcg dose) had a 6~nth post-vaccination serum
sample marginally positive for HBsAg (SIN"' 2.4).
The same serum sample was reported negative on
retest (S/N ~2.1). All other post-vaccination
samples, including the sample obtained · at 8
months, were negative for HBsAg. All serum
samples were negative for ant1-HBc. Alanine
aminotransferase levels were nonnal. The subject
developed anti-HBs at 3 months .
A ) 6 developed persistent cough and
t 1redness. He was seen by a phys 1c 1an
approximately 4 months after his second injection
(10 mcg dose) of vaccine and was tentatively
diagnosed as having chronic lymphatic leukemia.
The illness is felt not to be related to the
vaccine.
23981/4
1/16/86
Table 1
Antibody Responses MOng lnilia11y Seronegative HNllh Care Personnel Follcwlng

Vaccination with 5 or 10 111:9 Doses of Yeast Recalt>inant Hepatitis B vaccine
lot 819541/18011/C-l220 at 0, 1, and 6 flonths in Study 883
5g 10 mcg
'& vith Anti49s CIIT i■IU/111) \ with Anti-Mis <Ill i■IU/111}
Till!!! All ~rs All Aesoonders
(Rlmths) SIN~ 2. 1 111lU/■l ~ 10 Vacclnees SIN~ 2.1 11lU/111l ~ 10 SIN~ 2.1 mIU/ml ~ 10 Vaccinees SIN~ 2.1 111IU/ml ~ 10
-
2 e,ee!cs 13 (3/24) 4 ( 1/24) o.s 5. 4 10.4 4 (1/28) 4(1/28) 0.4 22.2 22.2
12 (3/25) 8 (2/25) 0.6 12. 4 16.1 14 (4/28) 1 (2/28) 0.6 15.5 50.9
2 59 (13/22) 41 (9/22) 5.3 23 .5 40.2 65 (11/26) 31 (8/26) 4.3 12.2 31.8
3 79 (19124) 54 (13/24) 10.1 21.1 40.3 86 (24/28) 64 (18/28) 11.9 21.9 34.3
6 81 (11/21) 51 (12/21) 10.8 20. 4 36.0 85 (22126) 85 (22/26) 30.3 46.7 54.4
118 100 (20/20) 95 (19/20) 215.l 215.3 259.0 100 (24/24) 96 (23/24) 863.2 863.2 1084.9
0
0
Ill
b
,0
23981/5
l/16/8ti
Table 2
PATIENT COUNT CltHICAl COt,PlAtNTS
RECot1BIHAHT HEPATITIS 9 VACCINE
STUOT I 088J
TREATttEHT
LOT NIJttBElf Cl220
DOSE 5 ttcG
PATIENT CLASS: ffEAlTlf CARE PERSONNEL
• TOTAL VACCIHEES I 25 PATUHTS I - DOSE l •

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION Q Hlltffl£R
CLINICAL
COMPLAINTS
•----------------------------------------------------------------------------1
• 0 • l • 2 • :S • 4 • 5 •
MITH
.COHPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••••••••-••••••••••tttt••••••••••••••••••••••••••••••••••••••••••••••I••••••••••
REACTION, LOCAL UHJl!CT. SITEI •• 1 •• 0 •• 0 •• 0 •• 0 •I 0 •• II 1
• ( 4.0Y.I • I O.OY.I • I 0.0"/.J • I 0.07.1. I 0.07.J. I 0.07.1. I I 4.0Y.J
-----------------------------------•----------•----------1----------1----------•----------l----------•----------•-----------
sOffENEss I 1 I o • o • o • o • o • I 1
I 1 4.o;o • 1 0.0;:1 • t 0.0;:1 • 1 o.or.1 • t o.or.1 I t o.o,o I I t 4.0;:1
-----------------------------------•----------1----------•----------•----------•----------•----------•----------1-----------
SYSTl:ttIC • 6 I 4 I 3 • 3 • 3 I 2 • • 7
I C 24.0Y.I I I 16.07.l • C 12.0:0 • t 12.0Y.I • t 12.0Y.I • C 8.07.1 I • I £8.0Y.I
----------------------------------------------------------------------------------------------------------------------------
I
WHOLE BODY/GENERAL I 3 I 2 1 2 2 l u 3
I , n.o;:1
c 12.0;:1 I c 8.0Y.I
• 4. Cir. I ( 8.07.) I 8.0)0 I 4.07.1
I
CfflllS I 0 0 0 1 0 0 l
O.OY.J ( 0.07.1 ( o.or., ( 4.0Y.I ( 0.07.) 1 o.o:o ( 4.07.J
SMUTIHa I 0 0 0 1 0 0 l
o. or. I ( ( O.GiO ( 4.or., ( o. 07.) 0.07.1 I 4.07.)
fATtGUE/lill!A~HtSS 3
0.07.1
2 l 2 2
' l 3
• 12.0)0 &.DY.I 4.0Y.J I 8.0Y.I I 11.07.J I 4.07.) I 12,07.1
'
(
lIG!fTHUOEO 0 0 0 l 0 D 1
• 0.07.J ( O.DY.J I O.OY.I t 4.07.1 I o.o;o ( 8.07. J I 4.DY.I
ACHtNE'5 I
I c
l
4.0lO • (
I 0
O.OiO (
0
o.ox, (
0
O.OiO '
I I
0
o.o;o I
0
0.01.1 (
l
4.D7.J
IHTEGUHEHTART SYSTEN
PRURITIS,ITCHIHG
.•
I•
(
1
4.07.) • (
I
•
I
0
o.o;o (
l
4,07.J (
0 I
I
0.07.J • (
•
0
0.07.J I
0
0.0)0 1.
2
"· 07.J
I 1 0 0 D I 0 0 l
I I 4.07.J • ( • 0.07.) ( t.07.J ( 0.07.1 • I o.o;o I o.o;o ( ,. 07.J
I I
PIMPLE I a • 0 1 0
•• I 0 0 l
0.07.) •• t o.o:r., ,.or., ( 0.07.1 o.o:o o.o:o I II. 07.1
'
(
0
0
U'I
U'I
0
Table 2 (cont . )
PATIENT COlMT CLINICAL Cml'lAINTS
RECot181NANT HEPATITIS 8 VACCINE
sruor 011113
lRUT"EHT
LOT HIJtllEI! cuzo
DOSE 5 t1CG
I TOTAL VACCINEES l 25 PATl(NTSI - 005E 1 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION • t1Ut18ER
CLINICAL l ------------------------------------------------ - - - ------------------------- 1 MITH
COttPLAINTS • 0 • 1 I Z • J • 4 I 5 I IC011PLAIHTS
......... ..... ................. .... . .......... . . . ..... . . . l••····· ·•• l••······ •• l••· · · · · ·•• l••······•• l••······••I••········
I I I I
RUPIR ATOl!Y I Z I 2 • l I l I l I l I I 3
a.ox, I , a.o::o I 1 4 .07.JI , 4.ox, I 1 4,01.1 I 1 4.ox, I I l u.o;o
I I I • I I I
llllflNITl!I I l I o • o I O I o I O I • l
4.0X) I I 0 ,07. J I I 0.07.) I l o .o,o I ( 0,01.1 I I 0.07.1 I I I 4 .o;o
I • • • I I I
UPPU RESPIRATORY t H,ECT •• HOS I Z I 1 I l I l I l I 1 I I Z
· a.o:o I t 4 .o:o I l 4 .o:o I , 4 .D7.I I c 4.o;o I l 4 .o:o I I , a.ox,
COUGH 0 l o I 0 0 1
4.o:o I • • 07.) 0,17.1 0,07.1 I 0,0'/.I 4 .07.1
' ' '
1 .0:0 (
DIGESTIV! STSTEt1 l 0 0 l l 0 z
4,07.1 0.07.J o.o;o •• , x, 4.07.1 o.or.1 ( 8.07. )
DIARRHEA 0
' 0
l
0
' 0
' 1
I
0 1
D.07.J a.or., 0.07.1 0. 07.1 4.0Y.I I o.o:o ( 4.07.)
'
( (
NAUSEA 1
' 0 0 1 0 0 2
4,0iO l 0,07.1 l o. or.1 ( 4.G7. I C 0,07.l l 0.07. l ( 8 . 01.)
DININISHED APPETITE 0 D 0 l 0 0 l
I 1 .0;0 ( G.o:o I 0.07.1 ( 4.0r. t l 0.0lO I 0.07. 1 ( 4 . 07.I
NERVOUS SYSTtt'I 0 0 Cl l l 0 1
0.07.) 4.0Y.I 4 .07.1 o.o:o 4 .0XJ
D.OY.) I
'
(
vtRTlGOIDI ZZIM£99 I D I
' o. or. t
D I D I 1 I
' 1 I
' O I I l
I c 1 .0:0 I c o.or., I I o.ox, I , •.o:o I , • . o:o • , o.o:o I I c 4 .or.,
-----------------------------------1----------1----------1
PERSONS MITH CDNPLA INTS I 7 I 4 I
----------1----------1----------1----------1----------1
3 I 3 I 3 I 2 I I
---. -------
a
I I za.o;o I I 16.o:o I I 12.07.) I l U,07.) I f U.07.) I I 8,0iO I I C 32.07.)
-----------------------------------t----------1----------1----------1----------1----------1----------
PERSOtlS WITH NO C011PUINTS I 18 I Zl I zz I ZZ I zz I Z3
1I ----------1-----------
I 17
I , 12.0:0 I c &t+.or.t • l M.oxt I , 8a.ox, I , 8&.0Y.I • c ,2 . 0:0 I I , 6&.or. 1
------------------------------- ---- 1---------- l----------•-- --------I----------I----------I----------I---------- I----------- O ·
PERSOHS WITH tlO DATA I O I D I O I O I O I O I I 0 0
• l a.or., I c o.or. 1 f , o.,x, I , o . ox, I , o.ox, I c o . o;o f I I o.o;o \II
...
IJ1
Table 2 (cont.)
PATI(NT Cotm CLINICAL CDHPLAINTS
R£Cot1BINANT HEPATITIS B VACCINE
STUIJY 088]
TRUTl1Uff
LOT NUM8ER Cl2to
DOSE 5 HCG
PATIENT CUS!II H£ALnt CARE PERSONNEL
I TOTAL VACCINl:ES C 25 PATlENTSI - DOSE t I

1----------------------------------------------------------------------------8
I DAYS POST VACClHATIOH I H\JlfflER
CLINICAL
Cot1PlAINT9
1----------------------------------------------------------------------------I
I O I 1 I I! I l I ,. • 5 I
NITH
ICONPUIHTS
•••••••••••••••••••••••••••..•••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l•••••-•••l••••••••••I••••••••••
-----------------------------------1----------l----------1----------l----------l----------l----------l----------l-----------
sYsTE111c I 1 I O I t I O I O I O I I 1
I c ,.,2Y.1 I c o.oY.1 I I o.o;o I , o.o:o I I o.o;o • 1 o.ox, • I , ,..ox,
------------------------------------1
WHOLE BODY/GENERAL I 1 I II I II I o I o I o I I 1
I ( o\.l!Y.I I ( 0.0Y.) I I 0.0;() I ( 0,07.1 I ( O.OlO I ( o.o;o I I I 4.0;()
I I I I I I I I
HUDACME I 1 I O I O I O I O I O I I l
I C o\.2:0 I I o.o;o I C 0.0iO I C 0.0:r.1 I C 0.0Y.I I C 0.0%1 I I I •.ox,
-----------------------------------l----------1----------1----------1---------I----------I----------I----------I-----------
PERSONS MITH CDfflllAINTS I 1 I II I II I O I O I O I I 1
I C 4.2)0 I I 0,0Y.) I C o.o;o I ( 0,07.1 I C 0.0Y.l I C 0.0Y.I I I C 4.0XI
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsDNs MITH NO CONPLAINT!I I 23 I to\ I Z5 I 25 I 25 • 25 I I Zit
I I n.a;o I uoo.o:o • 1100.01.1 I noo.ox1 • c100.ox1 I 1100.0;0 I • , 96.or.,
-----------------------------------1----------I----------I----------I----------I----------I----------I---------- I-----------
PERSDffS WITH HO DATA I O I O I O I O I O I D I I 0
I c o.o:o I c o.or., I 1 0.02, I c a.ox> I I o.o:o I , o.o;o I I c o.or.1
0
0
\JI
VI
"'
Table 2 (cont.)
PATIENT COUNT CLINICAL COHPlAINTS
RECON9INANT HEPATIT~S 8 VACCINE
STUDY 08113
TREATt1ENT
LOT NUHBER I Cl220
DOSE 5 t1CG
PATIENT ClA!I!: HEALTH CARE PERSOtHl
I TOTAL YACCINEE9 I 2ft PATIENTS I - DOSE J I

1---------------------------------------------------------------------------I
I DAYS POST VACCINATJOH I NUHBER
CLINICAL 1------------------------------------------••-------------------------------I NJTH
COHPlltNTS I O • 1 I 2 I J I 4 I 5 I ICOHPUINTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••-l•••••••••••••••••••••l••••••••••l••o••••••l••••••••••I••••••••••
I I I I • I I I
REACTION, LOCAL UNJECT. SITU I l I O I O I O I e I O I I l
I f 4.:s:o I t o.o:u I t o.ox, I I o.o;n I t o.ox1 I t o.o;o I I t 4,37.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
SOREHESS I 1 I o I O I o I o I o I I 1
I t 4.JXJ I ( 0.0,CI I f 0.0?.J I I ,.0Y.J I I 0.0Y.I I t o.o;o I I I 4.3?.I
---------· -------------------------1----------1----------l----------l----------l----------l----------l----------•-----------
sYsn:HIC I J I o I • I 1 I o • o I I J
I t 13.0XI I t 0.0,0 I I 0.0XI I ( 4.3¼1 I t 0.07.1 I t O.0XI I I t 13,0Y.J
NHOLE BODY/GENERAL I l
4,37.1 (
0
0,0lO I
0
0.07.I I
0 I
O,0Y.J I I •
o.o;o (
0
0.0?.I
I
I I
l
"· 37.)
I
HEADACHE I l 0 0 0 0 0 I 1
I C 4.3XI ( 0.0?.J I 0,0)0 I 0. 0Y.J t 0.07.) ( 0.0)0 I I 4.J:o
I I
IIESPIRATDRY I l
4.3)0 ( •
o.o:u I
0
0. 0Y.J I
0
0.0?.I (
0
0.0)0 ( •
O.0Y.I
I
I t
l
4,37.)
I
UPPER RESPIRATORY INFECT.• NOS I l 0 0 0 0 0 I l
4.37.J ( o.o,o ( o.o;o ( 0 .0?.I ( 0.0)!1 I 0.07.I I I 4. ]Y.J
I
DIGESTIVE SYSTEN I l 0 0 l 0 0 I 1
4.37. l ( 0.0)0 ( O. 0Y. J ( 4.:SY.I I o.or.1 I 0.0?.I Ic 4.3)0
NAUSEA I 1• OI OI 11 DI DI I l
I I 4,37.J I ( 0.07.J I I 0.07.J I ( 4,3iO I l o.or., I l o.or.1 I I f 4,:,;o
-----------------------------------•----------1----------1----------1----------•----------1----------1---- · -----•-----------
PERSONS NITff COHPUIHTS I 4 • 0 I O I l • 0 I O I I 4
I t 17.4Y.I I ( 0.0iO I t 0.0?.J I t 4.]Y.J • I o.o;o I I 0.0?.I I I t ,17.4:0
-----------------------------------1----------l----------l----------l----------•----------I----------I----------I-----------
PERsONS Wint NO CONPLAINTS I 19 • l!3 I l!3 I 22 I 2l I 23 • I 19
I I 82.67.J • uoo.oi:1 I 1100.0;0 I t 95.7Xl • uoo.01.1 I 1100.0:0 I I I 82,67.J
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
PERSONS WITH NO DATA I O • 0 I O I O I O I O I I 0
I I O.0Y.J I t I.0i(I I ( 0.0;() I ( 0.0?.I I I O.0XI I ( 0.0?.I I I t 0.07.1
0
0
"'
11'1
..... "'
Table 3
PATIDff COlm HA><lHUN TEHPERA~E9
RECot18INANT HEPATIT~S 8 VACCINE
STUDY 0118:J
TREATHENT
LOT NU!18ER I CUto
DOSE 5 t!CG
PATIENT ClA!IS: HEALTH CARE PERSONNEL
I TOTAL VACCINtES I 25 PATIENTS) - DOSE 1 ' •

1---------------------------------------------------------------------------------------•
I OATS POST VACCINATION I NUH8ER
nax TEltPERATUIIE
t DEt; F, OtlALI
1---------------------------------------------------------------------------------------•
• 0 I 1 I ! • J • 4' • 5 • •
· NITff
• nAX TEMP
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••I•••••••••••••••••••••
I • • I I I • •
< 99 • 22 I to • 22 • u • 24 • 24' • • 11
I • 1111.0%1 • • eo.o;r.I I « ae.o:o I , ea.ox, I • "6.ox, • • 96.o;o • I • 69.0Y.I
I I I • • I I I
•• - tJ9.9 I J • 4 I 3 I 3 • 1 I 1 • • 7
• I 12.0:0 I I 16.o:o I I 12.ox, I I 12.DXI • I 4'.DXI • I 41.0)0 I • ( ze.OY.I
• I I I I I • I
100 - 100. 9 I D • 1 • D I O • I • 0 • • 1
• • 0.01., I • ♦ .ox, I 1 0.01.1 I I o.o:o • , 0.01.> • 1 a.o;o I I • ♦ .010
------------------------•----------•----------•----------l----------l----------l----------•---------------------•-----------
TE11PEAATURE TAKEN • 25 I 25 • 25 I 25 I 25 • rs I • U
• 1100.ox, I 1101.01., • 1100.01., I 1100.ax, • 1100.01.1 I 1100.01.1 I I 1100.01.,
------------------------l---------l----------l----------•----------•----------l----------•---------------------I-----------
TE11PEAATURE NOT TAKEN I O I O I O I 0 I I I 0 • I 0
I I o. ox J I I o. o:o I I O. OX I I I I. ox l I I O. 11.1 I I o. ox I I I I o. OY. J
0
0
\11
Ill
,:.
Table 3 (cont. )
PATIENT COUNT NAXIt'Ult TEHPERAT\IRES
IIECDMBINANT NEPATI.TIS B VACCINE
STUDY I 0883
TREATitEHT
LOT NUMBER CLZZO
DOSE I 5 HCG
PATIENT CLASS: HEALnt CARE PERSOHNEL
• TOTAL YACCINEES ( Z5 PATIEHTSI - DOSE t I

1I ---------------------------------------------------------------------------------------•
DAYS POST VACCINATIOH I NUtff!ER
NAX TENPERATURE
IDE6F10RAU
l---------------------------------------------------------------------------------------1
I O I l I 2 I 3 • 4 • 5 • ·I
MITH
INAXTENP
····················-··•···················••l••······••
• I I
l•..•·••..··········••l••······••l••······••
I • I I
l••·····••RI••········
I
< 9'P I 19 I ZZ I U I 24 I Z3 I 2l I I 18
I I 82 , 67.1 I c 95, 7,0 • C 95,e:o I UDD,D7.1 I C 95.87. I I 1100.o;r.1 I I I 75 .oio
I I I I I I I I
99 - '9 .9 I 4 I I I l • o • 1 I o • I 6
I I 17,47.1 • C 4.3i0 I C 4 .2XJ I C 0.07.l I C 4 ,t7.J • I 0.07.J I I I 25 . 01.I
------------------------•----------•----------1----------•----------1----------•----------•---------------------1-----------
TENPERATURE TAKEN I n I n I 24 I 21t I 24 • 23 • I 24
I t 92.07.1 I C 92.01. J I c 96,07.J I I 96.07.J I c 9ft,07.I I I 92,07.l I I I 96.01.1
------------------------l----------
TE11PERAruRE NOT TAKEN I 2
l----------l----------l----------l----------•----------
I t I l I l I 1 I Z I
I---------------------I-----------
I l
I t 8.07. 1 I C 8.01.1 I C 4 .07.1 I C lt .07.1 I I 4,01.J I I e.01.1 I I I 4.0iO
0
0
~
U'I .
U'I
Table 3 (cont.)
PATIENT COUNT NAX1t1Utt TEHPERA1\JRE9
AECOt181HAHT HEPATJT~S B VACCINE
STUDT 088J
TRE ATNENT
LOT NU'l!t ll Cl 220
OOSE S 11CG
PATIENT CLASS HEALTH CARE Pt AS~L
I TOTAL VACCIH!ES C 24 PATIENTS) - OOSE J I

1I --------------------------------------------------------------------------------------
OATS POST VACCDIATIOH
I
I HU119ER
HAX TEHPERAT\.IRE
(DEG F, ORAll
l---------------------------------------------------------------------------------------1
I O I 1 I 2 I J • 4 I 9 I •
WITH
I NAX TEl1P
..•••••••••••••••••••••••••••••••••!•••••••••• •••••--••• ••--•••••• ••••••••••!•••••••••• ••••••••••l•••-••-•l••••••••-
1
NORHAl I 21 2 2 t ti t I 2
a.1)0 It s .n:, c s.r1., c a.1;0 c s.r1., I c e.nn t , a. 1r. ,
I I I
< n I 19 I 20 u 21 19 I n I 1a
82.6)0 I ( 8 7.0?.) ( 91. 3?.I ( 91.J)O I (
( 81!.61.I 91 ,JlO I I 78 .JiO
I I I
99 - 99. 9 I 1 I 1 o o 2 I II I 2
4 .3)0 I ( 4 .37.t ( 11 .0,0 ( ,.or. , C a.no I I O.DXt I C 8 ,7Y. )
I I I
101 - 1 01 , 9 I 1 I e o o o I II I 1
I ( 4. J)'.) I ( ,.111.t C D.01.t ( o.or., C I .OY.t I C 11.11:0 I I C 4.J)()
------------------------1I ----------1
TI:HPERAl\JIIE TAKEN n I ----------1----------1
n I n I ----------•----------•----------1---------------------1-----------
n • n I n I I n
• I '15.8Y.) • C 95.87.J • C 95,87.) • t 9S.8i0 • I 95.8Y.) I C '5,87.I I I C 95. 8i0
------------------------1I ----------1----------1----------1
TEl1PERATURE NOT TAKEN 1 I 1 • l I ----------1
l I ----------1----------1---------------------1
1 I 1 I I -----------
1
I I 4 , 2l0 I t 4.t?.J I C 4 .21.t I I 4 .tr.1 I C 4.UO I t 4.27.1 I I C 4 .2i0
O ,
0
I.II '
Ill '
0-
Table 4
PATIENT CC!l»IT CLINICAL COttPLAINT!I
REC0t1BINANT HEPATITIS 8 VACCIM£
!ITUOY oen
TREATttENT
LOT HUt19EII tltto
DOS£ 10 HCG
PATIENT CLASS! HEALTH CARE l'ER!K»l«L
I TOTAL YACCIN£ES C te PATIENTS I - DOSI! 1 I

Il----------------------------------------------------------------------------1
OATS POST YACCINATIOH I ~EA
CLINICAL
COl1PLAINT!I
•----------------------------------------------------------------------------1
I O I 1 I t I :, I 4 I 5 I
MITH
ICDMPLAIHT!I
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l•••••-•••l••••••••••la•••••••••
I I I I I I I I
REACTION, LOCAL !INJECT. !IITU I t I 1 I O I O I 0 I O I I t
. I ( I l l.6)O I ( 0.0Y.I I f D.0Y.J I I 0.07.) I I 0.0):) I
7,1)0 I I 7.lY.1
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
SOREN£S!I I t I 1 I o I o I o I o I I 2
I ( 7.1)() I ( l.61.J I ( o.o:o I ( 0.0Y.J I ( 0.01.1 I I 0,07.) I I I 7.17.1
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
STSTEHIC I 7 I Z I l I D I l I O I I 8
I f H.01.1 I f 7.liO I l 10.7XI I t o. ■7.J I I 3.6;o I t o.o:o I I 1 28.67.I
NHOLE BODY/GEtlEAAL I 7 1· z 0 1 I 0 7
25.07. I ( l.61.J ( 7 .11.1 ( 0.DY.I ( 3.67.J I • o.o;o zs.o;n
I
FEVER (TEMP, HOT REPCRTl!DJ I 1
l.6:i!J (
0
O. 0Y. I (
0
o.o,o ( •
o,o:r., I
0
0.0:r.1 I
D
I.OY.I
l
l.6Y.J
SM£ATING I 1 0 1 0 0 0 1
( J.6iO ( D. D7. I ( J.6?.I ( 0.0Y.I l 0.0,:1 ( 0.0)0 3.61.J
!ll!HSATION Of' NARtn11, 6EN!RAL I t

7.1?.J
•
D
o.o;o I
0
o.or.1 ( •
0.07.1 I
0
o.o:r., I
0
o.o;o
t
7.UO
PATIGUEl'Nl!A~tlE!IS I
t 10.7)0
l
•
1
J. 1,Y,J
•
1
].6i!J (
0
0.0iO •
0.01.1
0
0.0:r.1
l
10. T/.J
'
(
tlAlAISE I l D 0 0 I 0 0 1
l.61.J ( 0. DY. J ( 0,07.J I 0.01.1 I I 0.0)0 ( 0.01.J 3.61.J
I
HEADACHE I • I)
o. 07.J
0
0.07.I
0 I
0,07.1 I •
1
l, 67. J
0
0.07.J
1
3.67.)
' I
0.01.1 ( (
I
lll!!IPlRATORY I 1
:S.6)O
D
0. 0Y.J
0
o.or., l
D I
0.0?.I I I •
0.0)0 l
0
O.OY.I
1
3.6'0
' l
I
UPPER RESPIRATORY IHl'ECT., NOS I 1
J.6)(1 I
D
o.o;o I
•
0.0?.J (
0
o.o?.J
I 0
I C o. 01. I (
0
o.o;o
1
3.67.J 0
0
UI
"'
~
Table 4 (cont.)
PATIENT COUfT ClINICll COl1PLAINTS
RECot181NlNT HEPlTITJS B VACCINE
STUUY , oee:s
TREATHENT
lOT HU111!Elt Cl22D
OOSE 10 t1CG
PATIENT CLASS: HEllTit ClllE P!RSOHHtl
I TOTAL VlCCIHEES ( 28 PATIEHTSI - OOSE 1 I

1------------------------------------------------------------------------·-··1
I OATS POST VACCIHATIOH I NJl18ER
ClINICAl 1----------------------------------------------------------------------------I MITH
COffl'U IHT9 I O I 1 I 2 I 3 I • I 5 I IC011PlAIHTS
••••••••••••••••••••••••••••••••••• l••••••••••l••••-••••l••••••••••t••••••••••l••••••••••t•••••••••••••••••••••I••••••••••
I
CARDIOVASCULAR I 1 0 0 0 0 0 l
I I 3.6Y.J I o.or., I 0.0)0 ( O.OY.I ( O.OY.J ( O.OiO I l.61. I
I
HYPOTEHSION I l 0 0 0 0 0 l
I c J.6Y.) ( O.OY.J I 0.0)0 ( O.OiO ( 0.0:r.1 O.OiO I 3.67.1
DIGESTIVE STSTE~
I
I 0 1 1 0 0
' 0 l
O.OY.) I 3.6)() ( 3.67.l I 0.07.) I O.OY.) I O.OY.) I 3.6Y.l
NAUSEA
' 0 l 1 0 0 0 l
O.OY.J ( J.6l0 ( 3.67.l ( 0.07.l ( 0 .OY.l ( 0 .07.) I 3.6Y.l
OIHIHISHED APPETITE
' 0 1 0 0 0 0 I l
O.OY.I ( 3.6Y.J ( O.OiO C 0.07.1 ( 0. OY.J I O.OiO I I I 3.6)0
H[RVOUS SYST£H
' 3 l 0 0 0 0 I
I. I
I l
I 10.7Y.J 3.67.1 ( o.o;o I 0.01.1 ( 0.0)() ( O.OY.I I I 1 10.1:r.1
' I I
VERTI60/0IZZINESS 1
3.6)(1 ( •
O.DiO (
0
D.OlO (
0
o.o::o (
0
o.o;o (
0 I
o.or., I
I l
I I 3.6)(1
TffOUGMT It1Pllf!M[HT I l I O I O I 0 I O I 0 I I l
I 3.6)0 I I O.OY.I I I 0.07.1 I I o.o;o I f O.OlO I f O.OY.I I I I 3.6Y.I
I I I I I I I
TREHOR l 1 I l I o I o I o I I I I l
, J.6r.> I, J.6:r.1 Ic o.oY.1 I, o.o;o I, o.or.1 I, o.or., I II J.6iO
I
ffll6AHS OF SPECIAL SENSE I O I I Ol I o I O I O I I l
11.or.1 I
I o.o,n I ( J.6Y.I I C o.o;o I ( O.OY.I I I O.OY.I I I I l.6Y.J
I I I I I I I
COHJUHCTIVITIS I O I O I 1 I O I O I D I I l
I ( o.or., I I O.OT.I I I J.6Y.l I I 0.07.) I I o.or.J I I O.OY.I I I I J.6Y.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSotts NITit COMPLAINTS I 7 I 2 I 3 I O I 1 I O I I 8
I c rs.ox, I c 1.11.1 I , 10.1r.1 I I o.o;o I c 3.67.I I , o.ar.1 I I , t8.6lO
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I----------- 0
PERSotr.1 MITH HO COMPLAINTS I 21 I Z6 I 25 I 28 I 27 I 28 I I 20 0
I C 75.0)(1 I I 92,9)(1 I I 89.JY.I I 1100.or.1 I I 96 ••;o I noo.or., I I I 71.41.J I.Tl
\II
0,
Table 4 (cont.)
PATIENT COlffl CLI NICAL C0NPLAINTS
RECot1BIHAHT HEPATt~IS B VACCINE
STUDY 0883
TREATltENT
LOT NUmER I CU!20
DOSE to · tteG
PATIENT CLA!l!I : HEALTH CAR! PER!IOHMEL
------------------------------· ---------------------------------------------------------------------------------------------
• TOTAL VACCrHEU ( t8 PATIENTS) - DOSE 1 I
•----------------------------------------------------------------------------1
I DAYS POST VACCINATJOH I HUltBER
CLINICAL
CDHPU INTS
•---------------------------------------------------------------------------1
I O I l I t • l • - • 5 I
Mint
. COMPLAIHJS
•••••••••••••••••••••••••••••••••••••••••••••• l•••••••••••••••••--•••••••••••••••••••••••••••••••••••l••••••••••I••••••••••
-----------------------------------•----------l----------l----------•----------•----------1----------1----------1-----------
PERSONS WITH NO DATA • O I O I O I o • 0 I O I I 0
• I o.o;o I I O.Ol(J I I o.o:o I I , .o;o I I 0.07.) • C O.Ol() I 8 I 0.07. )
0
0
I.II
\II
~
Table 4 (cont. )
PATIENT COUNT CLINICAL COIIPLAIHTS
RECOHBINANT HEPATIT~S I VACCINE
STtJDY 111183
TREATtff:NT
LOT ~ER Cl220
DO!!! 10 t1CG
PATIENT CUSS: HEALTH CARE PERSONNtl
I TOTAL VACCINIE!S I 29 PATIENTS) - DO!! t I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION • flUl19ER
CLINICAL •----------------------------------------------------------------------------• MITH
tor1PLA1HTS I 0 I 1 I Z I 3 I ~ I S I ltotff'UINTS
•••••••••••••••••••••••••••••••••••l•••••••••••-••-••••l••••••••••l••••••••••l••••••••••l••••••••••l•••--••••o•••••••••
I I I I I I I I
REACTION, LOCAL UN.JECT. SITE) I 1 I O I O I O I O I O I I 1
I c J.6Y.) I c 0.01.1 I c o.o:o I c o.o:o I c 0.01., I c o.o:o I I c J.6Y.I
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
!IORENESS I 1 I O I o I o • o • e I I l
I c J.6'O I c 0.01.1 I c o.o;o I c o.o:o I c 1.0;0 I I o.o;o I I c J.67.)
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
srsTENIC I 2 I t I 1 I 2 I 1 I 1 I I 5
I l 7,lY.) I C 7.11.J I I J.67.1 I I 7.liO I C J.T,O I I 3.7iO I I I 17.97.1
NKDLE SOOT/GENERAL I t 1 1 l! 1 1 ~
I c 7.1)0 J.6)O 3.67.1 7.liO 3. T/.) I 3. T/.1 l n.JiO
SWEATING
I
I 1
' 1
' 0
' 0
' 0 0 l
J.6)O 3.67.) o.o:o o.o;o 0.07.) 0.07.1 J.67.J
FATIG\1£/WEAKNESS I 1
' 0
C
0
' t
' 1
' 1
J.67.1 C o.o;n I 0.07.) I 7.liO C J. T/.) I 3.77.) '
1~.JiO
ttAlAISE I •
0.0Y.I
0
o.o:o (
0
o.o:o
1
3.67.1
1
3. T/.) (
0
0.0)0
1
J.67.)
HUDACH! I 0
C
0 0
' 1
C
0 0 1
o.or., 0.OY.) o.or.1 0.0)0 J.67.I
O.0Y.I 3.6?.I
' I
C (
HOT ANO COlD FLASHES I 0 0

' 1 0 0 0 1
D.01O O.DY. I 0,DiO ,.or.1 O.OiO J.61.)
J.61.I I
'
( C
HOT FLASHIE5 I 0 l 0 D
' 0 0 1
0.0l'-1 I 0.Ol'-1 0.0iO o.or., 0 .DY. I I . 3.6?.)
RESPIRATORY I 0
' 3.6l'-I
l
I
I
I
0
' 0
' 0
' 1 t
D.OiO I 0.0iO o.o:o t.OY.I J.T/.) 7 .lY.I
PHARfflGITIS I SORE mROAT I I o·

I J.6Y.I
D
I
I
I
0
' 0
' 0
I
1 1
o. or., I o.o:o I c 0.0iO ( 0,0iO ( a.or., J.T/.1 J.67.)
' 0
0
VI
0-
0
Table 4 (cont. )
PATIENr COUNT CLINICAL Cot1PLAINTS
REC~DIANT HEPATI TIS B VACCINE
STUOY 0883
TRUfflENT
LOT NUl1BER CL22D
DOSE 10 t1C6
PATIENT CU S!I HE ALTlf CARE PERso.Ml
--------------------------------------------------------------------------------------------------------·
I TOTAL VACCINEES { 28 PATialTSI - DOSE t -------------------
I
1I ----------------------------------------------------------------------------I
DAYS POST VACCINATION I NU118ER
CLINICAL 1 ---------------------------------------------------------------------------- IICOHPLAIHTS
WITH
COt1PLAINT9 I O
, I 1
, I t I J
, I 4
, I !I
,
I
................................... .........• .......... .......... .......... ..................... ......................
UPPER RESPIRATORY I NFECT. • NOS I
I c
0 I
o.o:o I c
1 I
J.67.1 I I
D
o.o:o I c
I 0
e. o;o
I
I c
0 I
o .o:o I c •
o.o::o
I
I
I
I I
1
ll .67. I
I I I I I I I I
CARDIOVASCULAR I 1 I 0 I D I 0 I 0 I 0 I I 1
3.67.1 I c 0.07.1 Ic o.0%1 Ic t .0%1 I I o.o:u Ic 0 .07.1 I I I J ,67. )
I I I I I I I
PALLOR I 1 I 0 I D I 0 I 0 I 0 I I 1
3.67.) I I o.o:o I 1 o . o;o I, 0.0%) I I o.o;o I1 0 .07.I I I c 3 .6)0
I I I I I I I
DI GESTI VE SYSTE" I 0 I 1 I l I 1 I 0 I 0 I I t
o.07.1 I c J,6XI Ic J.6%1 I t 3.6l0 I C O.OXI I I O.OiO I I c 7 . 17.1
NAUSEA IO I 11 11 11 DI t i I 2
I c o.o;o I c J . 6XI I t J.6Y.I I t 3.6Y.J I t 0.07.1 I I o .o;n I I c 7 .17.J
-----------------------------------1----------l----------l----------1----------I----------I---------- I---------- I-----------
PERsONS NITH COHPLA INTS I J I t I 1 I 2 I 1 I 1 I I s
I C 10.710 I C 7. 110 I I 3.6%) I I 7,17.) I ( 3,no I C 3 .7%) I I I 17.9i0
------------. ---------------------- 1----------1---------- l----------l----------l---------- l---------- l----------l-----------
nRsDNS MITH HO CONPLAIHTS I 2s I t6 I 21 I u I 26 I 26 I I u
I I 09.:s::o I I 92.9%) I I 96. , :o I t 92.9%) I I 96.31.1 I I 96.3%1 I I I 82. 1%)
---------------------------------- ·1----------1---------- 1----------I---------- I----------I----------I----------I-----------
PERSOHS NITH HO DATA I O I O I O I O I O I I I I 0
I I o.0%1 I C 0.0%) I I 0.07.J I t 0.07.J I I o.a;o I I 0.0%1 I I I 0 .07. J
0
0
VI
-
C1"
Table 4 (cont.)
PATIENr COUNT CLINICAL COtff'UINTS
RECON8INAHT MEPATITJS 8 VACCINE
STUDY I 01183
mUffl!:NT
LOT NUl'IBER · 1 Clt2t
DOSE 10 HCG
PATIENT CLASS: MULllt C~ PPISOfH-l

1----------------------------------------------------------------------------
I DAYS POST VACCINATIOH
tI ffl.lt1BER
CLINICAL
COl1PUINTS
l----------------------------------------------------------------------------1
I O I 1 I Z I 3 I 4 I 5 I
WITH
lt0t1PUINTS
•••••••••••••••••••••••-••-•••••1I ••••••••••1••••••••••1
I I
••••••••••1••••••••••1••
I I
.. ••••••l••••••••••l••••••••••I••••••••••
I I I
REACTIOtft LOCAL CINJECT, SITU I 1 I 1 I O I 1 I O I O I I 1
I I 3,T/.) I ( 'J.T/.) I I o.o;o I ( 3,7?.) I ( 0.0?.) I I 0.0?.I I I f 3.71.)
-----------------------------------1----------l-----
sMENEss I 1 I
-----
1
l----------l----------l---------l----------l----------l-----------
I 0 I 1 I 0 I 0 I I 1
I I 3.7lO I ( 'J.T.I.) I I 0.01.) I ( 3.T.1.1 I ( O.0iO I ( 0.0)0 I I I 3.7:1.1
--------- ·-------------------------1----------1----------I----------I----------I----------I----------I----------I---------- .
sysnnrc I " I o I o I o I o I 1 I I "
I I 14.81.1 I I 0.01.1 I I 0.01.1 I I o,o,o I I o.o;o I I 3. T.1.1 I I I 14,111.1
I
MfOlE BODY/GENERAL I 0 I 0 I 0 0 0
"
"
14.111.) ( 0.OY.) I ( o.ox, I c 0,0lO 0.0Y.I I 0.0Y.1 I 14.81.1
I I '
FEVER ITEMP. HOT REPORTED) I 1
3.7'0 • I
I I
0
o.o?.t I I
I 0
0.0Y.I I
.a
o. 07.) I
0
0.07.1 I
1
3.T,O
FATIGUE"'4EAKNESS I 3
' 0.0?.)
0
I
I 0 I
I
0 0 0 3
11.11., ( t,07.1 I I 0.0Y.I I I o.o,o I O,0iO I 0,07.I I 11.lY.I
I I
ACHINESS I 1
3.7lO (
0
o.o;o I ,
I •
O.0Y.I
I
If
0
0.07.1 I
0
O.0lO I
0
o.or., I
1
3.71.1
I I
CARDIOVASCULAR I 1 II I II I 0 0 0 1
3.7XI ( O,0XI I I 0.0iO I I 0.07.1 I o.o:o I o.or.1 I J.T.f.l
I I
PALLOR I 1 0 I 0 I 0 0 0 1
3,7'0 C 0.01.1 II 0.01.1 I C o. 07.1 I 0.01.) ( o.o:o ( J. 77. J
CIGESTIVe SYSTEM I O I 0 I 0 I 0 I O I 1 I I 1
o.ox, I I 0.01.1 I I 0.0Y.) I ( 0.07.I I I 0.0:r.1 I I l.7Y.I I I I 3.7Y.I
I I I I I I I
NAUSEA I O Io I O I o I o I 1 I I 1
IC 0.01.1 I c 0.01.1 I l o.o:t.J If 0.0?.I I I 0.01.1 I l 3.71.1 I It 3.7i!I
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
,t11s01n Wint CONPLAIHTS I 4 I 1 I o I 1 I o I 1 I I "
I I 14.8:0 I I l.7:r.l It 0.D:t.1 If 3.71.1 I I 0.01.1 It l,7Y.I I I I 14. 8?.I 0
0
\II
(1-
1\J
Table 4 (cont_.)
PATIENT COUNT CLIHICAL COMPUINT9
RECotl&INANT HEPATIJIS 9 VACCltlE
STUDY 011113
TRUTl1ENT
LOT tM18ER I Cl220
DOSE 10 t1CG
PATIENT CU!IS: HEALTH CARE PERsotHL
I TOTAL VACCINEES I 27 PATIENTS! - DOSE 3 I

1----------------------------------------------------------------------------I
I OATS POST VACCINATION I NUH9ER
CLINICAL
COl1PLAIHT9
1----------------------------------------------------------------------------I
I O • 1 I ~ • 3 I 4 • S •
WITH
IC011PUINTS
••••••••••••••••••••••••••••--•-1•••••••••••••••••••••1•••••••••••••••••••••1••••••••••••••••••••••••••••••••1••••••••••
-----------------------------------1----------l----------•----------1----------l----------•----------1----------•-----------
. PERSONS MITH NO CotfPUINTS I D I 26 • U • 26 I 27 • H • I 23
I ( 85.27.l I ( '6.3?.l I UGO.DY.I I I 96.llO I tlOO.Ol!I I I "6.3i0 I I I 85.2l0
-----------------------------------1---------
PEIISDNS IIITH NO DATA I O
. 1----------1----------1----------I----------I----------I----------I-----------
I O I O I I I O I O I I 0
I ( o.o;o I I t.OY.J I I O.OY.I • I 0.0?.I I l O.OY.I I I O.OY.J I I I O.OY.I
0
0
\J'I
0-
1.,t
Table 5
PATJENT Cotffl NAXIHUH TEl1PERATUIIES
RECOMBJHI NT HEPATITJS B VACCI NE
STUDY : 0883
TRU TNENT
LOT Nllt1BER I Cl 220
DOS£ 10 t1CG
PATIENT CLASS: HEALTH CARE P£RSONNEL
---------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHtES t 28 PATIENTSt - DOSE 1 I
l---------------------------------------------------------------------------------------1
I DAYS POST YACCIHATIOH I Nllt1BER
NIX TEl1PERATUIIE
tOEC F , OR&Lt
1--------------------------------------------------------------------------------------l
I O I 1 I 2 I 3 I 4 I 5 I I
MITH
I NAX TEHP
••••••••••••••••••••to11••l••••••••••l••••••••••l•---••••l••••••••••l••••••••••l••••••••••l••-•••••• l•••••••••• I••••••••••
I I I I I I I I
< 99 I 11 I 21 I 24 I 26 I 24 I 22 I I 15
I t 60.71. t I t 96.4Xt I t as.1,0 I c 96.liO I c 118.9i0 I t 111.51.J I I c 53,610
I I I I I I I I
•• - 99 . 9 I 11 I 1 I 4 I 1 I J I s I I n
I ( 39.JlO I t J.6%1 I t 14.JlO I C 3.T~I I t 11.uo I ( 18.51.1 I I C ...6.4i0
------------------------l----------l----------
TEl'IPERATURE TAKEN I 211 I 28
l----------l----------
I 211 I 27
l----------l----------1---------------------1-----------
I 27 I 27 I I 28
I noo . 01. 1 I noa.o:o I n oo.01.1 I , 96.41.1 I 1 96.41.t I , 96 ... ,o I I noo.01.1
------------------------ Il----------l----------
n;HPHATVRE HOT TAKEN O I o I
l----------
O
l----------l----------l----------1---------------------1-----------
I 1 I 1 I 1 I I o
I t O. OiO I ( 0 .01.J I t 0 .01.1 I ( J,61.1 I I l.61.) I ( 3.61.1 I I ( O.OlO
0
0
Ill
c,.
~
Table 5 (cont.)
PATIENT' COUNT NlX~ TEttPERATUSIES
RECDt1BlNl NT HEPATITIS B VACCINE
STUDT 01183
TIIEAT"ENT
LOT NUt'IIER Cl21!0
DOSE 10 t1CCI
PATIENT CLASS HE ALTH CARE Pt RSOHNEl

1---------------------------------------------------------------------------------------I
I OAYS POST VACCINATIOH I NUt18ER
HAX TtHPtRATURE
COE& , . ORl lt
1--------------------------------------------------------------------------------------I
I O I 1 I 2 I J I " I 5 I I
MITH
f Nl X TEHP
••••••••••••••••••••••••l••••••••-1•••••••••• ••-•••••••••••••..••••••••••••••l•••••••••••••-••••••l•••••••••• I••••••••••
I I I I I I • I
< 99 I t" I• I
I I es.r.c,
21 • 21
'6.4i0 • ( '6 ...,o
•
•
26 I 26 I ts
I ,2.,,0 • I 96.JY.I I C 9 2 . 6)0 I
I I n
I C 75.0Y. I
I I I • • • I I
99 - 99 , 9 I " I 1 I l • 2 I l I 2 I I 7
I r 14.JY. 1 I r J.6Y.1 • r J.6Y.J I r 1.uo I , J.no I , 1. , r.1 I I , :s.o;o
------------------------1----------1
TEt1PERATUIE TAKEN I 28 I ----------•---------•----------1----------•----------1
28 I 28 I 28 I 27 I 27 I ---------------------1-----------
I 28
I 1100.07.1 I 1100.07.1 I 1100.0Y.I I U00.0)(1 I I 96.,x, I I 96.,x, I I ( 110.0iO
------------------------•----------
n HPERATURE HOT TAICEff I O Il----------•----------•----------
O • O • O
l----------•----------1---------------------1-----------
• 1 • 1 I I O
• C 0.0)0 I C a.or. , • C 0.0;:1 I ( O.OXI I I J.67.) • I J.6Y.I I I ( a.or.,
c:,
0
\It
CJ'
"'
Table 5 (cx,nt.)
PATIENT Cotm HAXINUH TEtfflERAT\JIIES
RECOteINANT HEPATITIS 8 VACCINE
STUIY 1 oes3
TRUTHENT
LOT NUt1BER I Cl2H
DOSE 10 t1CG
PATIENT ct.us: HEALTH CARE PERSa-lM!l
I TOTAL VACClNEES C 27 PATIENTS! - DOSE J I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION . I NU'18ER
HAX TlHPERAT\JRE
CDIESF,DRAU
........................ IO
,..........,
l---------------------------------------------------------------------------------------1
I
I l
..........
I
• t
..........,
•
I J
,I" • 5
................................
I • I
I
, , , MITH
.......... I.......... IHAXTEHP
I I
..........
< 99 I 19 I U I ts I 26 • 25 • 24 I I 18
I c 76.0XI I c es.2;0 I l '2,61.J I C 96.3,O I c ,2.6,0 I l 88.9'0 I I I 66.no
I I I I I I I I
99 - 99. 9 I 6 I " I t I 1 • t I J I I ,
I I t4.0lO I I 1,.11io I I 7.4,O I t J.7XI I c 7.4r.l I l 11.uo I I I JJ.3,O
------------------------1----------1----------•----------•----------•----------•----------I---------------------I-----------
TEHPERATURE TAICEH I t5 • 21 I 27 I 27 I t1 I l1 I I 27
I C 92.67.I I 1100.0;0 I ClCI0.07.) I ClOD.01.) I UIID.0lO I UGI.DY.I I I 1100.0Y.I
------------------------l----------1----------1----------1----------l----------l----------l---------------------1-----------
TEffl'ERATUl!E NOT TAICEH I t I D I O I O I O I O I I 0
I I 7.4Y.I I C 0.01.) I C 0.07.) I I 0.0Y.I I l 0.0Y.I I l O.0Y.I I I I 0.0Y.I
0
0
"'a-
0-
u,
co
a:,
►
Q
.:::,
t-
en
00567
PROGRAM: Yeast Recombinant Hepatitis 8 Vacc1ne, Study 885

recombinant hepatitis B vaccine among healthy adults
who are negative for hepatftfs 8 virus serologic
markers.

Lot 81990D/18066/C-L215
817668/18061/C-L216
819910/18068/C-L211
81992A/18070/C-L219
81954I/18071/C-L220
PRIMARY Alan I. Leibowitz, M.D.

University of South Florida
School of Medicine
Tampa, Florida 33612
SECONDARY John T. Sinnott, M.D.

INVESTlSATOR: Ben 6. Yango, M.O.
University of South Florida
School of Medicine
Tampa, Florida, 33612
STUDY LOCATION: University of South Florida Medical Center

Tarapa, Florida 33612
Affiliated hospitals and other area health facilities.
DATE INITIATED: July, 1985
STUDY POPULATION: The study population will consist of approximately 250

healthy adults of either sex (excluding pregnant
women), who are negative for hepatitis B virus
serologic markers, have normal liver function tests
and have not prebiously received any hepatitis 8
vaccine.
32271/1
1/20/86
00568
Study 885
PROCEDURE: Participants are assigned to one of five lots of

vaccine. stratified by sex and age (50 persons per
lot). All study subjects receive a 10 mcg dose
intramuscular injection of vaccine at o. 1 and &
110nths. Participants are asked to record their
tellll)eratures and any local or syste111ic c~laints for
ftve days after each injection.
Blood samples are obtained prior to vaccination and at
l, 2. 3, 6. B, 12 and 24 months post initial
injection. All specimens are assayed for HBsAg,
ant i-KBs, and anti -HBc by MSDRL. ALT 1 eve ls wi 11 be
tested pre-vaccination and at two and eight 1110nths
post initial injection at the University of South
Florida. Samples with an ant1-HBs titer >25 mlU/ml
may be tested for anti-A and anti-g_ activity~ Samples
may also be assayed for yeast antibody at MSDRL.
RESULTS: HEALTHY ADULTS

10 mcg Lot 81990D/18066/C-L215 at o. 1. and 6 months
10 mcg Lot 817668/18067/C-L216 at o. 1. and 6 months
10 mcg Lot Bl991D/18068/C-L217 at o. 1, and 6 months
10 mcg Lot 81992A/18070/C-L219 at o. 1. and 6 months
10 mcg Lot 819541/18071/C-l220 at 0, 1, and 6 months
Injection No .
Lot _1_ ....L ...L
819900/18066/C-L215 0 0 0
817668/18067/C-L216 0 0 0
81991D/18068/C-L217 50 0 0
81992A/18070/C-L219 50 50 0
81954l/18071/C-L220 50 50 0
Ho serologic results are currently available.
3. Clinical Compla1nts:
There have been no serious or alarmtng adverse
32271/2
l /20/86
en
00
00
>-
Q
.....::,
VJ
PROGRA~: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,
Study 889

l. Mentally retarded individuals who are negative
VACCINE: Yeast Recombinant Hepat1t1s B vaccine

Lot 993/C-K937 (20 racg/HBsAg/ml)
PRIMARY Robert P. Perrillo, M.D.

INVESTIGATOR: Director, Gastroenterology
St. Louis, Missouri 63125
SECONDARY Oliver H. Lowry, M.O.

INVESTIGATOR: Department of Phanaacology
Washington Univ. School of Medicine
STUDY LOCATION: Beverly Fams Foundation

Godfrey, Illinois 62035
DATE STUDY INITIATED: June 19, 1985

mentally retarded individuals, above 5 years of age,
and 50 health care personnel, who are negative for
HBsAg, anti-HBc, anti-HBs, have a normal ALT and have
23941/1
1/3/86
00570
Study 889
STUDY PROCEDURE: Mentally retarded indiv1duals are randomly assigned to

one of two groups, stratified by sex and age. Health
care personnel constitute a third group.
Mentally retarded individuals receive a 0.5 ml (10 mcg
HBsAg) or a 1.0 ml (20 11eg HBsAg) intramuscular
injection of vaccine at 0, 1, and 6 months. Health
care personnel receive a 0.5 ml (10 mcg HBsAg)
intramuscular injection of vaccine according to the
same regimen.
at 1, 3, 6, 10 and 24 months.
All serum samples are assayed for HBsAg, anti-HBc and
anti-Hes. The pre-vaccination and 3 month post-
vaccination samples are also tested for ALT. Samples
may be assayed for yeast antibody. In addition,
samples w1th an ant1-HBs titer ~ 25 mIU/ml may be
tested for anti-! and anti-1t subtype specificity.

10 mcg Lot 993/C-K937 at 0, 1, and 6 months
: Injection No.
l_.l_
I
_l_ _L
! 88 82 74
One person with an initial ALT level approxi-

mately 1.5 times nonDal (69) received vaccine. A
post-vaccination ALT level is not yet available.
Three month post-vaccination samples will be
tested for ALT.
23941/2
l /3/86
00571
Study 889
RESULTS: (Contd) 2. Serologic Results:

Serologic data at 1 month are available for 82
health care personnel.
At l month 17% (14/82) of vaccine recipients
seroconverted (S/N ~2. l) and 6S ( 5/82) developed
protective levels of antibody (mIU/ml ~10). The
GMT for all vacc1nees was 0.5 mIU/ml at that ·
time. Among responders with a titer of S/N ~2.1,
the GMT at 1 1110nth was 6.3 mIU/1111. while for
responders with a titer of mIU/ml ~10 the GMT was
25 mIU/ml.
health care personnel following two injections of
vaccine. Clinical c011plaints and raaxi~um
temperatures reported following each injection
are provided in Tables 1 and 2. In sunnary:
I Freauencv bv [niection No.

Clinical Comolaint 1 2 -.:.3---1
Injection Site 1 (1 /82) 0 {0/82) NA

Systemic 5 (4/82) 6 (5/82) NA

A 37 year-old female noted facial wamth and
flushing 14 hours after receiving the first
injection of vaccine. Within the next 3 hours
she developed facial urticaria. She was treated
with cold packs. All sympt011s subsided within 12
hours. The subject was treated with 8enadry1
prior to the second and third injections, and had
no post-vaccination reactions.
2394[/3
1/3/86
Table 1
PATIENT cotMT CLINICAL CtlttPLAtNTS
RECONBINANT HEPATITIS B VACCINE
STUOY : oee,
TRUTHENT
LOT NUt18ER I CK937
DOSE I 10 t1CG
PATIENT CLASS~ HEALTH CARE PERSOt&IEL
I TOTAL VACCINEES C &2 PATUHTSI - DOS[ l I

I1----------------------------------------------------------------------------I
DAYS POST VACCIHATICH I HUffllER
1----------------------------------------------------------------------------I
CLINICAL
COMPLAINTS
,
I O •
,
1 I t
,
• J • 4
, I 5 •
, WITH
,
ICOflPLAIHTS
................................... .......... .......•.. .......•.. .......... .......... ..........•.......... ..••.•....
I • I I • I I
,
I
REACTION, LOCAL UNJECT. SITU I O I l I O • O I O I O I I 1
I C o.o,o I C 1,tiO • C 0.01.1 • I 0.0;:1 I t 0.0;:1 I C o.or.1 I I t l.ZiO
-----------------------------------l----------l----------l----------l----------l----------l----------•----------l-----------
so1ums!I • o • 1 I o • o • o • o I I 1
• 1 0.0;:1 • t 1.2;:1 I r o.o:o I I 0.0;:1 • r 0.0,:1 • c 0.01.1 I I 1 1.2;:1
-----------------------------------1----------•----------1----------•----------1----------•----------•----------1-----------
SYSTEHIC I l • t I I! I O I O I O I I 4
I 1 1.21.1 I c t.11r.1 I l 2,4;:1 I c 0.01.1 I l 0.0;:1 I c 0.01.1 I I I 4,9;:1
MHOLE BODY/GENERAL 0
I• r o. 01.I
t 0 0
o.or., •
o.o;:,
0
0.01.1
2
2.'IY.I
' t.41.1 0.01.1
'
C C ( (
FLUSH •I 0 1 0 0
• 0 1
I c o.or., I 1.2Y.J 0 .01.J o.or., o.or., 0.01.J 1.2%1
'
C ( C
HEADACHE
I
I 0 1 0 0
' D D l
o. or., o.or.1 ( 0,0)0 0.01.J 0 .01.) I 1,2iO
1.21.1
' ' '
(
ITCHING, FACIAL I 0 1 0 0 D 0 l
I I 0.0%) ( 1.21.1 I o.o:n ( 0.01.1 ( D. DY. I ( 0.01.J I 1.21.1
I
URTICARIA, FACIAL I 0
0.01.1
l
1.21.1
0
0.01.1 ( O.OlO
0
I •
o.o;o I
0
o.o:o
1
1.21.1
'
(
DIGESTIVE SYSTEM I 1 1 1 0 D D
I
I
' t
1.tlO ( 1.21.) I 1.2;!) ( 1.01.J ( D. 0% I ( •• 01.1 I I 2.41.I
I I
NAUSEA I l I
1.21.1 I t
1 1
l.ZY.I
0
D.01.I
0
0.07.J I •
0.0;:1
I
I I
2
2,'11.1
I
'
l.tXI (
I I
VOf'IITING I 0 I
I
I
1,27.I
0
o .ar.1
0
0.0;:1
0
o.o:o •
a.or.,
I
I I
1
1.27. I
'
0.01.1 c ( (
N£RVOUS SYSTEM I 0
I
I 0 l 0
' 0 D
I
I 1
O.DiO I t 1.2r.1 I 0.0;:1 0.0;:1 0.01.1 I c 1.2:r.1
0.0%1 I
' ' 0
0
VI
....a
N
Table 1 (cont.)
RECOMBINANT HEPATIT~S 8 VACCINE
STUDT 0889
TR EATt1£HT
LOT NUMBf:R CK937
DOSE 10 t1CG
PATIENT CLASS: HEALTH CARE PERSOt!NEL
I TOTAL VACCIN£ES I 82 PATIENTS J • DOSE 1 I

1········-·······-··----···········-···--·············--···-··-···--·--------1
I DAYS POST VACCINATION I HU'18ER
1 •-··········-··-···-····-··•····•··•·•·····-····•·•·-········--·-·----··-·-·1
CLINICAL
COlfPU INTS
................................... I
,
I
O
.......... I 1
I
,...........,
I t
..........
I
I 3
,
..........
I
I "
..........
I
I
, 5
..........
I
I
, MITH
.......... !COMP ,I ,
LA INTS
......... .
I
PARESTHESIAS I O I O I 1 I O I O I O t t l
I I 0.01.) I I o.or., I I 1.2l0 I I o.o:o I C o.o;o I I o.o;o I I C 1. 27.)
·--··--···-·---·----···---··-·---··1···-------1
PERSOHS MITH COT1PUIHTS I 1 I
·------···1
3 I
-··-······1
I? I
-·-··-·-·-1--········
O I O
1····--···-1··-···--··1···········
I O I I 5
I c 1 .27.J I c 3,77.J I I z•._r., I I o.ox, I t o.ox1 I I 0.01.1 I I 1 6 . 11.1
·····-··· ······--··-·········-·····1··········1
PERSONS wnM HO c0t1Pu1ms I 81 I
··········1
79 I
··········1·-·-··-···1··········1·····-···-1
eo I az I 82 I 82 I
··········1-···--·····
I 11
I I 98,&iO I I 96.37.J I c .,7.61.1 I noo.OY.J I 1100.07.1 I 1100.0;0 I I t 'lll.97. 1
--···-······-·-·-··--····-·········1···-··-··-1
Pl!RSOHS WITH HO DATA I O I
----······1-·······-·1·-·---····1----------1--·----···1-···-·---·1
O I O I O I O I O I I
-·---···-·-
0
I I 0 .07.) I C 0.07. J I I o.o;o I I 0.07.J I I 0,07.) I I o .or.1 I I I 0 . 0?. J
0
0
...,
!JI
""
Table 1 (cont.)
PATIENT COUHT CLINICAL COttPlAINTS
RECOl1BINANT HEPATIJIS 8 VACCINE
91\J!JT 0889
TRUTl1ENT
LOT NU18UP I C1(937
DOSE 10 1'1CG
PATUNT CUSS: HEALTH CARE PER~L
I TOTAL YACCINEU I ez PATIENTS) - DOSI!'. t '

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I .tlUNaER
CLINICAL
COHPLAINTS
1----------------------------------------------------------------------------I
I O I 1 I Z I l I 'I I 5 I
WITH
IC011PLAINfS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
snn111c I o I z I 2 I 1 I Z I 1 I I 5
I c 0.01.1 I c z."1.t I c 2.1.1.1 I 1 1.zx1 I c 2.1tY.1 I c 1.zxt I I 1 6;1;0
NHOLE BOOT/GENERAL I 0 1 1 I D I D 1 t
0 .OY. I I 1.2)0 I 1.2:0 I < O.OY.I I o.o;o ( 1.27.1 I 2.--7.1
I
Hl!:ADACHIE I( 0 1 1 I 0 0 l z
O.OY.l ( 1.2'0 I 1. 27. l I I 0.01.1 t 0,07.l I 1.27.1 I 2.'17.l
lNTEGUt1ENTARY STSTEN I 0
o.o,o I
0
0.07.1 ( •
o.o;o (
0
O.OY. I I
1
1.27.J I
0
0.07.1 (
1
1.21.1
l'IPURITIS/ITCHING I 0
,.oio ( •
O.OY.I I
0
0. 07. l I
0
o.o:o I
1
1.2Y.I I
0
t.07.J (
1
1.2)0
RESPIRATORY I 0 0 0 0 1 0 1
O.OY.I ( o. 07.1 ( O.OY. l I O.OY.I ( 1.2:0 ( 0.07.l I l.tY.J
TONSILLITIS I 0 0 0 0 1 0 1
I 0.01.) ( 0.01.1 I O.OY. I I o. 01.) ( l.!1.l ( o.o:o ( 1.27.l
OIGESTIVE SYSTEH I 0 1 l 1 0 0 l
I 0.01.1 ( 1 .ZY. I I 1.27.1 ( l.ZY.I ( 0.01.) ( 0.07.) ( 1. 21.)
NAUSEA I 0 1 1 1 0 0 1
o.o:o 1.uo I 1. Zi:1 l ,ZY.1 I D,DiO I l,2Y.I
YOl1ITIHG I I I
(
1 I 1 I
' l I
O.DY.I
o I
(
o I I 1
I ( 1.01.1 I ( 1.2)0 I I l,ZY.l I I 1.21.1 I I 0,0)0 I f 0.07.I I I ( 1.ZY.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH Cottl'UINTS I I I Z I 2 I l I Z I 1 I I S
I I 0.01.1 I C 2.'ilO I I t.41.1 I t 1.27.l I I Z.4Y.I I I 1,ZY.l I I c 6.lr.t
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSCNS WITH NO COl1PUINTS I ez I 80 I eo I &l I eo I 81 I I 71
I Cl00.0)0 I I 97.61.1 I I 97.6Y.I I I '>8.81.1 I ( '>7.61.l I I ,e.er.1 I I I 9:S.9i0 0
0
11'1
-,a
b
Table 1 (cont.)
PATIENT COUNT CLINICAL COffllUINTS
RECot1BINANT HEPATITIS B VACCINE
ST\JIJY 011&9
TREATI1EHT
LOT NUtlBER CK'JJ7
DOSE 10 11CG
PATUNT ClA95: HEALTH CARE PIR!IONNEL
I TOTAL VACCINE ES ( ez PATIENTS, - DOS£ z I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUNIIER
CLINICAL
COl1PLAINTS
l----------------------------------------------------------------------------1
I O • l • Z I 3 I 4 I 5 I
NITff
ICOt1PlAINTS
•••••••••••••••••••••••••••••••••••l•••-•••••••..••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------1----------l----------l----------1----------•----------I----------I----------I-----------
PERSONS NITH NO DATA I O I O I 0 I I I O I O I I 0
I , o.o:o I c o.o:o I r o.oio I c o.oY.J I c o.oY., I , o.oio I I c 0.01.,
0
0
\J1
.....
"'
Table 2
PATIENT COUNT HAXIt1Utt TENPERATUIIES
RECOl181NlNT ffEPlT~Tl!I S VACCINE
!ITIJ!IT 01189
TRUTHENT
LOT tUIBtw tK'fJ7
DOSE I10 t1CC
PATIENT tlAS!ll ffEALTif CARE PEl!SOHN£L
I TOTAL VACCIHEE!I f 82 PATIENTSI - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DAYS POST VlCCIHATIOt4 I tl\Jlffl[R
NAX TENPERAT\JRE l---------------------------------------------------------------------------------------1 NJTH
(DEC F, CRALi I O I 1 I Z I 3 I 4 I 5 I • I NA)( tt:MP
•••••••••••••••••••••••••••••••••••••--••••-1•••••••••••••••••••••••••••••••••••••••••-l•••••-••••••••••••••t••••••••••
< 99 70 I 67 I 60 I 68 I 6& I 69 I 50
• 87,5:o I c 84,111.1 I < ao.01.1 I f 88.3?.l I f 89.5?.I I C 89,6%1 I• I t 61. 71.1
I I I I I I I
99 - 99.9 I 7 I 11 I 12 I 9 I 7 I 8 I I 25
8,T/.1 I ( 13.9)0 I ( 16.07.J I C 11.TI.I I l 9,27.1 I c 10.4?.J I I t 30,97.1
I I I I I I I
100 - 100,9 I t I 1 I 3 I 0 I 1 I 0 I I 5
Z,5Y.I I ( 1,31,1 I < 4,0Y.I I ( o.or.1 I , 1,3;.1 I , 0.0?.I • I I 6.21.)
101 - 101. 9 I l I o I o I o I o I o I I 1
I 1 1.21.1 I I o.o:o I I o.oY.1 I , ,.or., I 1 0.0,:1 I l 0.01., I I 1 1.r;o
------------------------t----------1----------1----------1----------t----------t----------t---------------------l-----------
I I I I I I I I
TENPERATURE TAKEN
I
80
C 97.61.I
79 75 77
I I 96.]?.J I I 91.57.1 I l
76 77
'3,9?.I I C ,z. n:, I ( 81
93,9%1 I I I 98.87.)
------------------------l----------l----------l----------l----------l----------l----------1---------------------1-----------
Ttffl'ERATUIIE HOT TAKEN I I! • l I 7 I 5 I 6 I 5 I I l
• C l!,4:0 • I 3.TI.I I ( a.s:o I I 6.17.I • C 7,]?.I I C 6.11.; I I I 1.21.1
0
0
I.II
....i
0'
Table 2 (cont.)
PATIENT COUNT HAXJHUl1 TEHPERATURES
RECOt18INlNT HEPATIT~5 8 VACCINE
5ttJIJY 08119
TRE.llt1ENT
LOT HUtmER Cl(937
DOSE r 10 t1CG
PATIENT CLASS: HEALTH CARE PER!IONMEL
• TOTAL YACCINEES ( 82 PATIENTS) - OOSE t •

•---------------------------------------------------------------------------------------•
• DAYS POST YACCJNATIOH I HUl18ER
•---------------------------------------------------------------------------------------1
ttAX TE"PERATURE
I DEG F , OR AU •
I
0 •
I
1 I Z
,
•
• 3
I
• 4 •
•
5 •
,
•
•
, NITll
I t1AX TEtff'
.............................................. ................................ ................................ ..........
• I
< 99 • 69 • 10 • 76 • 76 I 73 • 76 • • 61
• ( eq.i,o • I es.q7,J • I 92. 7:0 I C 92. T,O • ( 90.llO I C 92, T/.J I I I 71't.q?,J
99 - 99.9 I• 12 •
• 9 •
• 4 •
I 4
•• e I• 6
•
• I• 17
• c 14,67.I I I 11,07.J • c 4.t?.J IC .ri.9;0 I I 9.97.1 I I 7,37.J I I c 20.T/.J
• • • • I •
100 - 100. 9 • 1 I 3 • t I t • o I o •• I
• 4
• C l,ZY.I • ( J.T,'-1 • C Z.47.1 • C Z.41.1 • ( 0.0?.) I C 0.0?.I • • C 4.9;0
------------------------1----------t----------l----------t----------t----------l----------t--------------------t-----------
TEHPERATURE TAKEN f ez I 82 I et • 82 I 81 • 82 I f ez
I noo.ox, I uoe.oiu • 1100.11.1 I uoo.or.1 • c 98.87.1 I 1100.01.1 I I uoo.o?.J
------------------------1----------•----------•----------t----------1----------1----------1---------------------1-----------
TEHPERATURE NOT TAKEN I O I O I O I O • 1 • O • I 0
I C 0,0)0 I I O.D1.) • ( o.e:o I C 0.07.) • ( 1.vo I C 0.0?.) I f C 0.0?.)
0
0
...,...,
U1
00578

Study 891
PURPOSE: To compare the antibody and clinical responses to

recombinant hepatitis B vaccine and plasma-derived
hepatitis B vaccine a[llong healthy adults and children
markers.
VACCINES: l. Yeast Recomb1nant Hepatitis 8 Vaccine

Lot 0027L (20 ~cg HBsAg/ml)
PRIMARY Dr. Hu Zong-Han

INVESTIGATOR: Department of Biological Products Inspection
Bureau of Pharmaceutical and 81o1og1cal Inspection
Ministry of Health
Temple of Heaven, West Gate
Beijing, People's Republic of China
SECONDARY Dr. Sh1 Guiyong

INVESTIGATOR: Director of Epidemic Department
Chinese Medical University
Shen Yang, People's Republic of China
STUDY LOCATION: Shen Yang Municipal Anti-Epidemic Station

DATE STUDY INITIATED: December, 1985
STUDY POPULATION: The study population consists of 200 healthy adults

and 200 healthy children of either sex (exluding
and HBs, have a normal ALT level and have not
32121/1
1 /17/86
Study 891
STUDY PROCEDURE: Participants are grouped by age and randomly assigned to

rece1ve the yeast recombinant or plasma-derived
hepatitis B vaccine as follows:
Population Vaccine Dose Nll!ber R \ffll!n
Adllts Recorbinant 10 111Cg SO 1.0 1111 intr111111scular

(~30 years) injection of vacc\
at 0, l, and 6 IIIOllth
2 Adllts 10 n:g SO 1.0 1111 intrMUscular

( 18-29 years) Injection of vacci
at 0, 1, and 6 month
3 Olildren 5 IIIC9 100 0.5 1111 intraruscular

(5-10 years) injection of vacd
at 0, 1, and 6 months
4 Adults Plasina 20 mcg SO 1.0 ml intranLtscular

(?30 ye.rs) \njection of vacc\
at 0, 1, and 6 IIDR
s Adults 20 mcg SO 1.0 ml intrilllllseular

(18~ ye.rs) injection of vacci
at 0, 1, and 6 111011ths
6 Olildren 10 mcg 100 0.5 1111 intrn,scular

(5-10 years) injectlon of vaccin&
at 0, 1, and 6 lll)l'lths
Study participants or the participant 1 s parent or

guardian record their temperature or that of their
child, and any local or systemic complaints for five
A blood sample 1s obtained from each study participant
approximately two to three weeks before the first
injection of vaccine. Post-vaccination blood samples
are obtained at 1. 3, 6, 7, 8, 9, 12, and 24 months.
All serum samples are assayed for HBsAg, ant1-HBc,
anti-HBs, and ALT.
32121/2
l /17/86
00580
Study 891
RESULTS: (Contd) To date 100 adults and children have received one
injection of yeast recombinant or plasma-derived
hepatitis B vaccine. No serious or alaming reactions
Clinical follow-up data and serolog1c results are not
32121/3
1/17/86
00561
PROGRAFII: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,

Study 894
PURPOSE: To compare in111unologic responses to yeast recombinant

versus plasma hepatitis B vaccine in homosexual niales
and to compare differences, if any. in adverse
reactions to the two vaccines.

Lot 978/C-K.563
Plasma-Derived Hepatitis 8 Vaccine (HEPTAVAX)
Lot 1014/C-'4252
PRIMARY B. Frank Polk, ~.o.

INVESTIGATOR: Director, Infectious Disease Epidemiology Program
Johns Hopkins Univ. School of Hygiene & Public Health
Baltimore, MD
SECONDARY Lois Eldred, P.A.

INVESTIGATORS: Robin Fox, M.S.
Edward Fuchs, P.A.
Richard Kaslow, M.D.
Nancy Odaka, M.H.S.
Rachel Solomon, ~.H.S.
STUDY LOCATION: The Johns Hopkins Hospital

Baltimore, MD
DATE INITIATED: Apr11, 1985
STUDY POPULATION: The study population consists of 300-350 homosexua 1

males who are negative for all hepatitis B 111arkers and
have not received any hepatitis B vaccine. The 11en
are concurrently enrol led in a study to help the AIDS
research effort (SHARE) at the Johns Hopkins
University Hospital.
32161/1
1/17/86
00582
Study 894
PROCEDURE: Eligible participants are randomized to receive an

injection of either 20 mcg plasma or 10 mcg
recombinant vaccine at 0, 1 and 6 months.
Part it ipants are asked to record the1 r temperatures
for S days after each injectipn and to note any local
or systemic complaints.
Bloof specimens are obtained prior to vaccination and
at 1, 6, 9 and 12 months post 1n1tial injection.
After the first year of follow-up, serum samples are
collected every 6 months for another two years.
Baseline serum samples ire assayed for HBsAg, anti-HBs
and ALT. Follow-up serum samples are tested for
development of ant1-HBs antibodies.
RESULTS: HOMOSEXUAL MALES:

10 mcg Lot 978/C-K563 yeast recombinant at 0, 1 and 6
months
20 mcg Lot 1014/C-f!l252 plasma at 0, 1 and 6 months
n ect on No .
Vaccine ..L _2_ ..L
Yeast Recombinant 81 ()3
Plasma 88 70 0
2. Sero1og1c Results:
No serological results are presently available.
32161/2
1 /17/86
00583
Study 894
RESULTS: (Contd) 3. Clinical complaints:

and 1 participants following injections one, two,
and three of yeast recombinant vaccine, and for 88
and 67 participants following injections one and
two of plasma vaccine. SpecH1c complaints and
maximum temperatures reported during the 5 days
following each injection are provided in Tables 1
through 4.
There have been no serious or alarming adverse

reactions attributable to either vaccine to date.
Frecuen~ ;n i blf In,i!S:tion No.

Type Vaccine 1 2 _3_
Injection Recantbinant 30(25/83) 35(21/60) 0(0/l}

Siu Plasaa C2(37/88) 36(24/67)
15ystaic Aecalbinant 29(24/83) 18( 11/60) 0(0/1)

PlaSllll 35(3\/88) 25(11/67)
32161/3
1 /17/86
Table 1
PATI[NT COUNT CLINICAL COl1PLAIHTS
STUDY 08'14
mumENT
LOT IOIBER CK563
DOSE
10 M:.'G
• TOTAL VACCIHEES I 87 PATIEHTSI - OOSE 1 •
•----------------------------------------------------------------------------1
• OATS POST VACCIHATIOH I N1Jt111ER
CLINICAL
COHPUIHTS •
I
0 •
I
1
...........................................................
I
I!
, I 3 I
,
4 • 5 I
,
•----------------------------------------------------------------------------•
I
,
WITH
I COMPLAINTS
.......... .......... .......... ..........•..........•..........
I I I • I
REACTION, LOCAL I INJECT. SITE> • 15 I 14 I 8 I 4 I 2 I 0 I I ts
I , 1e.s:o I c 16.97.J I c ,.67.I I 1 4.97.1 I c 2.sr.1 I , o.or.1 t • , 30.17.J
-----------------------------------1----------•----------1----------1----------1----------1----------1----------1-----------
SOREHESS I 14 • 1ft I & I 4 I 1 I o I • 23
I I 17,37.l I I 16,97.l I I 9.6?.I I I 4,97.1 I I 1,27.l • I 0,07.1 • I I 27.71.l
I I I I I I I I
STIFFNESS/TIGHTNESS • 0 I D I O I O I 1 I O I • 1
I I D.07.) I I O.D7.) I I O.OY.I I I 0.07.1 I I 1,27.J I I 0.0;,;1 I I I 1.2:r.,
I I I I I I I I
HEt1ATOHA I 1 I o I O I O I O I O • I l
I ( 1.27.) I I 0.07.1 I I O.OY.J I I 0.0?.J I I o.o;o I I 0.07.1 I I I 1.27.1
-----------------------------------1----------1----------1----------1----------1----------t----------1----------t-----------
SYSTEl1JC I 9 I 11 I 13 I 11 I 3 I 4 I • 24
• I 11. 17. I I I 13. 3?. I • I 15 • 7X l I C 13. 41. I I I 3. T/. l • I 4. 97. I I I I 28. 91. I
WHOLE BODY/GENERAL I 2 5 I 4 2 1 2 10
2 .57.J I 6.0:r.1 I I 4,87.l t 2.41.1 ( 1.2,0 ( Z.SY.l I lZ.07.1
I
ctfILLS I 0 0 I I 0 0 0 1
0. 01.) I 1 l,2Y. I ( 0.0Y.I 0.0Y.) I 0.0iO ( l. 27. I
0.01.1
'
(
I
FATIGUE/NEAKHESS I 0 5 I 2 1 1 1 6
o.o;o 6.0:r.1 I 1 2.47.1 ( 1.2:r.1 1.27.1 ( 1.2;0 ( 7 ,27.I
'
(
HEADACHE I 0 0 1 1 a 1 2
o. 07.1 ( a. o:r.1 ( 1.2;0 ( 1.27.1 ( 0,07.l ( 1.27.1 ( 2.47.J
CHEST PAIN I 0 0 1 0 0 0 1
I c o. 07.1 ( 0. 07. I ( 1.2:r.1 ( 0.0:r.1 C 0.0)0 ( o.ox1 I ( 1.2:0
I I I
lIGfffflEAOED I 2 0 0 I 0 I 0 0 I 2
I c 2.5)0 I o. 07.1 ( a.ox I I , o.o;o I 1 0.0iO ( o.o:o I ( 2.liiO
I I I I
INTEGUl1EHTARY SYSTEH I 0 0 l I l I 0 0 I 2
0.07.1 I 0,0)0 ( 1.27.1 I I 1.2,0 I c 0.07.1 C 0.0;.1 I ( 2.4¼1
0
0
VI
0,,
g::
Table 1 (cont.)
STUOY OIi~
TREATMENT
LOT N\Jt'SER Cl<563
DOSE
10 M:'G
--------------------------------------------------------------------------------------------------------------------'
-------
I1----------------------------------------------------------------------------I
DAYS POST VACCitfATION I tl\Jl18ER
CLINICAL
Il----------------------------------------------------------------------------1
WITH
COMPLAINTS 0 I 1 I 2 I I
I 3 4 5 I ICOHPLAIHTS
****•••~•••••••••••••••••--••--••••I•••••••••• ••••••••••I•••••••••••••••••••• ••••••••••l•••--•••••1••••••••••1••••••••••
I I
RASH, NOS I 0 D I 0 1 0 I 0 l
o.o:o ( o.o;o I 1 o.o;o ( 1,27.) ( O.DY. I II 0 .OY.I ( 1.2:0
I I
OTHER I 0 D I l 0 0 I 0 l
o.o:o ( 0,07.1 I C l.2Y.I ( o.o:o f O.OY.I I C O.OY.t ( 1.z:o
I I
RESPIRATORY I l 1 I 1 2 1 I 1 2
1,27.1 I l,2Y.> IC 1,27.) ( 2Jtl0 ( 1.21.1 I I 1,2Y.t ( 2.47.)
I I
PHARYNGITIS fS!mE TltROATI I 0 0 0 l 0 I 0 l
I I 0,07.1 ( o.o;o ( 0.01.) ( 1.2)0 ( o.o;o ( O.OY.t f 1.£7.1
I
UPPER RESPIRATORY INFECT., NOS I 1 1 l 1 1 1 1
1,ZlO ( 1,£)0 f 1,27.) ( 1.27.1 f 1.21.1 ( 1,27.1 f 1.27.1
I
HEHIC AHO LYMPHATIC I 1 1 1 1 1 l 1
1.27.1 ( 1.27.) f 1.2i0 ( 1.2:iO 1.tlO 1.!7.)
' (
( 1.27.1
LYl1PtfADEHOPATHY, GENERAL 1 1 l l 1 l l
( 1.27.1 ( 1.2:1.1 ( 1.£7.1 1.2;:1 I
HUSctJLOSKELETAl 4 I 3 6
' 4
1.21.1
l
I 1.2)0
0
I l.Zi!I
II
( 4.9)0 t 3.67.) 7.21.) 4.9i!) o.o;n
ARTHRAlGIA, t10HOARTICUlAA 1 0
' 0
' 0
' l,t7.t
0
I
0
( 9.67.I
l
( 1.tY. I t 0,0)0 0,07.J o.o;o t o.or.,
' ' O,OY.I
( ( 1.zr.1
ARTHRAlGIA IOTHERJ t t 4 l 1 0 5
( t,SY.I I ( 4,8;'.) 1,27.1
2.4Y.I
' D.DY. I 6,07.)
( l ,2T.I ( I
11Y05ITIS l 1 l l 0 0 l
1.2)'!) I l, tY.I f l,2i!) ( 1.27.J ( o.or.1 ( D. 07. J I , l.ZY.l
I
nTALGIA I 1 1 1 1 0 0 l
1.21.) ( 1.21.1 1.::r., i.zr.,
ttuSClE STIFFNESS
I
I a a
' 0
' 1
( 0.01.I
D
( 0.0:1.)
0
( l,ZlO
l
0,07.I I o.o;o ( O.OY.) ( 1,2)() ( 0.07.) ( 0 .OY.) ( l.Z?.I
0
.,,
0
0,
111
Table 1 (cont.)
STUIIY 089ft
TREATMENT
LOT NU113ER Cl<S63
DOSE
10 MI;
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCitlEES I 87 PATIENTS) - DOSE l I
l----------------------------------------------------------------------------1
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------1
I O I 1 I I! I l I 4 I 5 I MITH
ICOt1PLAIHTS
••••••••••••••••••••••••••••••••••••••••••••••I•••••••••••••••••••••••••••••• ••••••••••I•••••••••• ••••e•••••I••••••••••
I I I
SORE CHEST I 0 I 0 1 1 D I D I 1
0.o;o I ( 0.0lO C 1.27.1 ( l.2Y.I C 0.07.1 I f 0.07.1 I I 1.27.1
I I
DIGESTIVE SYSTE" I 1 I 2 2 l O O I 6
1.27.1 I I 2.47.I C 2.t•Y.I I 1.27.I I 0.07.1 f 0.07.1 I I 7.2;0
I
DIARRHEA I O O l O D O I 1
D.07.I ( O.o:o C 1.2:0 C 0.07.1 C 0.07.1 C 0.07.1 I I 1.27.1
I
NAUSEA I 1 2 0 l Cl D I 4
1.27.1 C 2.41.1 I O.o;o I l.2%1 I D.07.1 I 0.07.1 I C 4.87.1
I
VONITING I O 1 o o O O I 1
o.o:o ( 1.2)0 ( 0.07.) ( 0.0%1 C o.o::o C 0.0%) I f 1.2%1
0THU I O O l o I O II l
0.0)0 C 0.OlO ( 1.2%1 I O.0Y.I C 0.07.t f 1.07.1 I ( 1.2%1
I
Ul!OGENITU SYST£t1 I O O l l D O I l
o.o;o C 0.0%) I 1.2%1 I 1.2:1.1 ( D.OlO ( 0.0Y.) I I 1.2:0
I
KIDNEY PAIN I O O l l 0 0 I l
I f O.o;o f 0.07.1 C l.2lO I 1.2:1.1 C 0.0?.I I 0.0%1 I I l.2iO
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsONs WITH COMPLAINTS I 21 I 2l I 19 I ll I s I 4 I I 42
I c 25.910 I c 27.Jl!I I c 22.97.1 I I 15.97.I I c 6.2;0 I I "·9;0 I I I 30.6?.I
-----------------------------------1----------t----------l----------l----------l----------1----------I----------I-----------
PERSON! MITH NO cot1PLAIHTS I 60 ( 60 I 6ft I 69 I 76 ( 77 ( I ftl
I C 74.UO ( C 72.37.1 I C 77.llO I C 84.llO ( ( 9l.81.) I I 95.1)0 ( I f 49.4i0
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH NO DATA I 5 I ft I 4 I 5 I 5 I 5 I I 4
I C 5.8;() I C 4.67.) I ( ft.6~1 I I s. 7Y.I I C 5.8%1 I f s.eY.I I I I 4.6?.)
C)
0
\JI
OD
- 0-
Table 1 (cont.)
STUDY 0894
TREATMENT
LOT NIJNBER CK56l
DOSE
10 M:G
------------------------------------------------------
I ·---------------------------------------------------------------------
TOTAL YACCIHEU I 63 PATIENTS I - DOSE Z f
•----------------------------------------------------------------------------1
• DAYS POST VACCINATION I HUtll!ER
1----------------------------------------------------------------------------f
CLINICAL
COHPUINTS
................................... •
, 0 I 1 • Z
..........•.........••..........
I I I
• 3 •
,
°' •..........•..........
.....................
I
5 •
•
WITH
I COMPLAINTS
.......... ,
• •
,
•
REACTION, LOCAL !INJECT, SITU I 16 • 11 • 5 I O • 0 • 0 • I 21
• I 26,7XI • ( 18.11.1 f ( 8,5:o • I 0.01.1 f I 0.0iO • ( 0.0Y.I • I I 35.0Y.I
-----------------------------------1----------•----------•----------1----------1----------t----------t----------1-----------
SOREHESS I 16 • 11 I 5 • O • 0 I O • • Zl
I C 26. 7?. I I ( 18. li!I I ( 8, 57.1 • I O, o;: I • I O, o;: I • ( 0. o;: I I • I 35. 0lO
-----------------------------------1----------l----------l----------l----------l----------l----------•----------•-----------
srsnHic • 5 I • I 6 I 6 I 5 • 3 I • 11
• C 8.31.1 • ( 6.71.) I C 10.z;:, I C 10.z;:1 I I 8.3?.I I I 5.1%) • • I 18.1%)
!ODY/GENERAL I z 2
NtOLE
3. 37.) (
3
5.01.I (
3
5.17.1 I "
6.87.l I 3.3)0 (
1
1,TI.I I
5
8.3%)
FATIGUE/WEAKtlESS I 1 t z 3 z 1 3
l. 77.1 ( 3.3:t.l ( 3.4:t.l ( 5,1:t.l ( 3.3%) ( 1.7)0 ( 5.07.)
CHEST f'AIH I 0
0. 0?.) ( •
0.07.1 (
0
0.07.1 I
1
l. 77.1 (
0
0.0Y.I (
0
0.0%) (
1
l, 71. I
LIGHTHEAOEO I 1 l 1 0 0 0 l
1. 71.J ( 1.7)0 ( 1,7)0 I 0.0?. I I 0.07.1 ( o.or.1 ( 1. 77.J
IHTEGUMEHTARY SYSTEN ,. 0
0.07.J (
l
1, Tl.I (
1
l.7iO I I • 0
0, 0?.J (
0
0.0JO (
0
0.0?.I . (
l
1. 77.1
OTlfER I
I I
I
0
O,0lO (
1
l. 77.1 I
1
I
1. 7?.I I• I
0
0.0?.I I
0
0.0Y.I (
0
O.0iO .
I
I
(
1
1,77.I
RESPIRATORY 0 0 1 I 1 0 0 I I 1
•• I 0. 07.t ( 0.07.t ( 1. 7Y.I I C l, 77.1 • I• •
o. 0?.I I I 0.07.1 I I I 1.7)0
UPPER RESPIRATORY INFECT., HOS I•

• I
I
0
0. 07. I (
0
0.01.1 I
1
1.7:t.l
I
I•
I
I
1
1.TI.I
•
•• I 0
0.0XI • I
I
•
I
0 I
0.07.I I
•
•
.••
I
(
1
1. 77.J
lf.JSCULOSI\ELET AL I l l 1 I 1 I• 2 I 1 I I l
l. 77.1 ( 1. 77. I I 1.71.1 • ( l . T/.1 I I 3. 3Y.t • C 1. 77.1 I I I 5.0JO
0
0
~
a,
-..a
Table 1 (cont.)
!!TIJDY 0894
TREATMENT
LOT IIUl18ER CK56'3
DOSE 10 M:G
I TOTAL VACCINEES C 63 PATIENTS! - DOSE 2 I

1----------------------------------------------------------------------------1
I DAYS POST VACCIHATION I NUt18ER
CLINICA L
COIIPlAINTS 1
I ----------------------------------------------------------------------------I
O I l I 2 I 3 I 4 I 5 I WITH
ICOt1PUINTS
•••••••••••••••••••••••••••--•-•••I•••••••••••••••••••••••••••••• ••--••-*• l•••••••••• l•••••••••• f•••••••••• ••••••w••••
I I I
ARTHRALGIA, 110HOARTICULAR I l O o O I O I O I I l
1,7)0 C o.o:o ( o.o;o ( 11.0Y.l I I O.OY. I If O. OY.I I I f l.7X I
I I I I
ARTHl!AlGIA IOTHER) I II l l 1 I 2 I l I I 2
0. DY. I ( 1. 7Y. l C l. 7Y. I C l. T/.1 I I 3. llO I f 1. 71. I I I I 3. 37. J
I I I I
DIGESTIVE SYSTEM I 2 II 1 2 I 2 I l I I 4
3.3Y.J C O.OY.J C 1 .71.1 I 3.4Y.I I I 3.3Y.I 11 1.71.J I 11 6.1;0
I I I I
DIARRHE A I 2 O I 1 I 1 I 1 I I 3
I 3,3;0 I e.01., I o . o;o C 1.T/.1 I I 1.?Y.J 11 1 .7X) I I ( 5.0Y.I
NAUSEA I 1 II 1 1 l l 2
1 . 71.l I G.O?.J I 1. 7?.l C 1. T/.1 ( 1. 7Y.J I 1 . 7?. I I 3. lY. l
VOMITING I l 0 1 1 1 l 2
1. T✓. I ( 0 .O?.I ( 1. 71.1 I l . T✓. l I 1.7;(1 I 1 . 7)0 I 3.lY. I
ABDONEH DISTENDED I D D D 1 1 0 1
O. IIY.l ( 0. O?. l ( 0 .07.1 ( 1.77.1 I 1.71.l I o.o:n I 1 . 7Y.l
U!OGEHITAL SYSTEN I 0 0 0 1 1 0 1
0. DY. I ( O.OXI C o.o:o I l.T/.1 I 1. T/.1 I o.or.1 I 1. 77.1
KIDNEY PAI N I 0 II 0 l 1 0 l
D.OY.J ( 0.0)0 ( 0. 01.1 ( 1.1r.1 I 1.TI.I ( O.OY.J ( 1. 71.)
PSYCH IATII I C/8EHAYIORAL I 1 1 1 0 0 0 1

1. 71.J C 1, Tl.I ( 1, 71.J I O. DY. I I O.OiO I D.DY. I I 1.7i0
DRU MS, BI ZARRE , Ut«ISUAL I l I 1 I 1 I O I O I O I I l
I I 1.7i0 I I 1.T/.) I I 1 .7Y.I I I O.OY.I I I O.OY.l I ( o.or.1 I I I , 1.7)(1
-----------------------------------l----------l----------1----------I----------I----------I----------I----------I-----------
PERSONS WITH COMPLAINTS I 20 I 1' I 11 I 6 I 5 I 3 I I 28
I I 33.lY.l I ( 25.0Y.) I I 18.6Y.J I I 10.ZY.I I I 8.3?.) I I 5 . 17. l I I I 46.7;(1
-----------------------------------1----------t---------- l----------l----------l----------l----------l----------l-----------
PERSOHS WUH HO COl1PLAIHTS I 40 I 45 I 40 I 53 · I 55 I 56 I I 32
I I 66.77.1 I C 75.0XI I ( 81.4Y.I I I 89.87.I I I 91.71.l I ( '4.9Y. I I I I 5:S.l:t.l
0
.,,
0
;JD
OD
Table 1 (cont.)
PATIEIIT CO\JHT CLINICAL COHPLAINTS
STUDY 0894
TREATMENT
LOT N\JflSEI! Cl'56'S
DOSE 10 r-L'G
I TOT AL VACCltlEES ( 63 PATIEHTSl - DOSE 2 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATlotl I NUtlBEI!
CLINICAL
COHPUINTS
1----------------------------------------------------------------------------I
I a I I I Z I 'S I 4 I !I I WITH
ICOMPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l•••••••••• l•••••••••••••••••••••l••••••••••l••••••••••l•••••••••• l••Q•••••••
-----------------------------------1----------
PERsONS WITH NO DATA I Z
I----------I----------I----------I----------I----------I----------I-----------
I Z I Z I Z I Z I Z I I Z
I ( 3 . ZY.I I C J , Z,O I C 3.3Y.J I ( 3 . 3)0 I ( 3.ZY.I I ( 3, 37. I I I ( 3.z;o
0
0
\II
OD
,()
Table 1 (cont.)
PATIENT COUNT CLINICAL COHPU IHTS
STUDY 0894
TREl ll11:HT
LOT NUl18ER CK56l
DOSE
lOM::G
I TOTA L VACCINEES I 1 PATIENTS I - DOSE 3 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUl18ER
CLINICAL
Cot1PU IHTS
l----------------------------------------------------------------------------1
I O I 1 I t I l I ti I 5 I MITH
ICot1PUINTS
••••••••••••••••••••••.. ••••••••••• l••••••••••l•••••••••• l••.. •••••• l•••••••••• l••••••••••l•••••••••• l•••••••••• l••a•~•••••
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSDllS MITH CotlPLAINTS I O I O I O I O I O I O I I 0
I C 0.07.1 I C 0.0)() I C O.OlO I ( O.OlO I ( a.oz, I C o.o::o I I I a.oz ,
------------ .----------------------I----------
PERS0t1S MITH t!O COt1PUIHTS I 1
I----------I----------I----------I----------I----------I----------I-----------
I 1 I 1 I 1 I 1 I 1 I I 1
I (100.0ZI I (100.0)() I (100 . 0)() I 1100.0XI I (100.0ZI I (100.0)() I I 1100.0XI
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS MITH NO DATA I a I O I o I o. I O I O I I o
I C o.o;o I C a.ox, I C o.o;o I ( o.o:o I ( o.o:o I ( a.o:o I I I a.oz,
0
0
~
.Q
0
Table 2
PATIENT COUNT " AXIH\Jt1 TEHPERATURES
STUDY OMlt
TREATttENT
LOT Hllffl!£R Cl<S63
DOS£
10 MX
~-------· • TOTAL VlCCINEES C 87 PATIENTS! - DOSE 1 I
•---------------------------------------------------------------------------------------1
• DAYS POST VACCINATION I NU'18ER
" AX TEHPERATURE
CDEG F• ORALI
1
•
---------------------------------------------------------------------------------------•
0 • 1 • 2 • 3 I 4 I S • •
WITH
• " AX TEMP
..•••••••••••••••••••'"'•••••••••••••••••••••••l•••••••••••••••••-••l••••••••••I••••••••-••••••••••••••••••••••• ••••••••••
L I• 2 1•
2 1 •1I 1 1I
1 1 1I 1 1I 1
l 1 I 2
!.67. J •
• ( 1. 27. J I C 1.27.J • ( 1.2;0 I I 1,Zl!I • 1 ,37.) 2 , 4;0
C
I I I
64 73 • 76 • 7S
~ I 7lf
~ I n7111 I I "
C· 83. l XJ •
• C 91.27.J • I C 92. 7l0 •I C 93.87.1 I- I 92.Sl!I I. I 90.97.) - 73.57.J
I I
99 - 99,9 11 • 4 I 4 • 4 •I It I s 16
•
14,37.J • C S.07.J I C 4.97.J •I c S.07.l I C S.1117.I • C 6.57.J ll.9,37.1
I I I
100 - 100.9 0 •I l I 1 0 • 1 I 1 3
0.07.J • C 1.27.J • C •
1.27.1 • l a, 07.J •• I 1,2)!1 • I 1 .3)!) 3.67.)
101 - 101 ., I o I 1 I o I o • o I o I I 1
I c o.oz, • c 1.27.J • c o.o;o • c o.o;o I I o.ol'-1 • c o.oz , • • c 1.2z1
------------ ·-----------l----------l----------•----------l----------l----------l----------1---------------------•-----------
TEl1PER ATUl!E TAKEN I 77 I 80 • 82 I 80 I 80 I 77 • • 83
I f 88.57.1 • f 91!,07.) I C 94.37.) I f 92,0iO I C 9Z.0)0 • C aa.s:o • • I 95 . 47.)
------------------------•----------l----------l----------•----------
TEHPERATUl!E NOT TAKEN • 10 I 7 • S • 7
l----------1
I 7 •
----------1---------------------I-----------
10 I • 4
I C 11.57.J I I 8.0)0 I f 5,77.) • C 8.07.J I I C,.07.I I C 11.57.1 • • C 4,67.J
0
0
\II
- -
,4)
Table 2 (cont. )
PATIENT COUNT HlXIl1Ut1 lEHPERATURES
STUDY 1894
TREATHENT
LOT HUtfl!ER CK563
DOSE
10 r-L'G

l---------------------------------------------------------------------------------------1
HAX TEHPER AT\JRE 1---------------------------------------------------------------------------------------I MITH
(DEGF,ORALI I II I 1 I 2 I 3 I 4 IS I I IHAXTE11P
••••••••••••••••••••••••I••••••••••••••••••••--•••••••• •••••••••••••••••••••••••••••• ••••.,.~••• l••••••••••I••~•••••••
NORt'IAL I 3 3 3 l 3 3 I l
5. llO C 5.3:f. I ( 5.4:f.) C 5 . 4)0 I 5 . 47.l I 5.57.l I I 5 . 3:'. I
I
< 99 I 44 49 49 44 45 46 I 35
77.2)0 ( 86.0lO ( 87.5)0 ( 78.67.) I 80.4Y.) I 83.6)0 I l 61.4)()
I
99 - 99. 9 I 9 4 2 6 a s I 15
1s. e;o C 7.11:f.l ( 3,6)0 C 10.7:f.l ( 14.]iO I 9.1:0 I C 26 . ])(I
I
100 - 100.9 I 1 1 2 J o 1 I 4
I ( 1 .8)0 I ( 1 .e;o ( 3.67.) I 5,4;0 I 0 , 0Y.) I C 1 .11:0 I I 7 . 0)0
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEHPERATVRE TAKEN I 57 I 57 I 56 I Sfa I Sfa I 55 I I 57
,o . s:o , , ,o.57.) 1 , e11 • .,,o , , e11 . ,Y.1 , , e11 . 9Y.1 1 , e,.:s:o 1
1• , , n.s:1.,
------------------------
TEHP£RATURE HOT TAKEN
l-------
I 6
.--1----------
I 6
I----------I----------I----------I----------
I 7 I 7 I 7 I 8
I---------------------I-----------
I I 6
I ( ,.s;o I C ,.s;o I ( 11 .liO I I n .uo I ( 11.lY.) I ( 12.77. 1 I I I 9.57. )
0
0
"'
-0
I\J
Table 2 (cont.)
PATIENT COUNT HAXIHUH TEHPERAT\IRES
STUDY 08 94
TREATMENT
LOT tMfflER CKSU
DOSE
=10 M:G
I TOTAL VACCIHEES I l PAT IENTS) - DOSE 3 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCI NATION I NUHBER
HAX TEMPERATURE 1----------•-----•-·-·--------·-··-------------·-•--·-------------------------•--------I WITH
(DEG F, OR ALI I 0 I l I Z I 3 I 4 I 5 I I I HAX TEHP
•••••••••••••••••••••••• l••••••••••••••••••••• l•••••-••• l••••••••••••••••••••• l•••••••••• l•••••••••• l•••••••••• I••••••••••
I I • I I I I I
NORMAL IOI ol l l 11 11 11 Io
I I 0.07. J I I o.o:o I uoo.o:o I noo.o;o I uoo.o;o I U00.0lO I I I o.o;o
I I I I I I I I
<99 I o I l I o I D I o I o I I l
I I o.o:o I 1100 . 0lO I I o.o;o I I o.o:o I I o.o;o I I 0.0lO I I uoo.o:o
------------------------1----------1----------1----------1----------1----------1----------1---------------------1-----------
TEt1PERATURE TAKEN I O I l I 1 I l I l I l I I l
( I o.oz, I (100.0X) I 1100.ox, I (100,07.) • 1100.ox, I (100.07.) I I 1100.07. )
------------------------l----------•-------·-·1----------1---------- 1----------1----------•---------------------l-----------
nHPERATIJRE NOT TAKEN I 1 I o I o I o I o • o • I o
I 1100.07.) I ( o.ox, I I 0.07.) I ( a.ox, I I o.o;o I ( 0.07.) I I I o.or.1
0
0
II\
.c,
~
Table 3
PATIENT COU.T CLINICAL COHPLAINTS
STlltlY oe,4
TRU.fflENT
LOT NUl18ER Ct125Z
OOSE
20 M:G
I TOTAL VACCINEES I 88 PAlIENTSI - 005£ 1 I
l----------------------------------------------------------------------------1
I OATS POST YACCIHATI~ I ~ER
CLINICAL .
COMPLAINTS
l----------------------------------------------------------------------------1
I O • 1 I Z I J • 4 • S I
WITH
ICOHPLAIHTS
•••••••••••••••••••••••••••••••••••1••••••••••1•••••••••••••••••••••1••••••••••1••••••• .. ••••••••••••••••••••••••••••••••••
I I • I I I I •
REACTION, LOCAL UHJECT. SITEI I 2l I 17 I -, I 4 I 1 I l I I '37
I 1 27.47.1 I c 1,. 3l!I I c 10.3l!l • c 4.n!J I c 1.1:1.1 I c 1.27.1 • I c r.2.ol!1
-----------------------------------1----------•----------l----------1----------l----------•----------1----------l-----------
soRrnEss I 23 • 17 • 9 I 4 I 1 • 1 I • 37
I I 27.4:t.l I c 19 . 3l!I I c 10.37.1 I f 4. 77.J I c 1.1::0 • c 1.27.J • I l 42.07.l
-----------------------------------t----------•----------l----------1----------•----------1----------1----------1-----------
srsrentt I 12 I 22 I 15 I , I 7 I 7 I I 31
I I 14.37.1 I { 25.07.I I { 17.27.) I I 10.s::o I I e.o::o I I e.1:0 I I C 35.27.l
----------------------------------------------------------------------------------------------------------------------------
I
MIIOLE OODY~GENERAL I 9 15 7 7 6 4 I I 24
10. T.1.1 I 17.0iO { 8.0Y.1 I e.i:o I 6.9)0 I 4.7::o I I c 27.ll!I
I I
Ct/ILLS I 0 1 0 0 0 0 I I 1
0.0%) ( 1.17.1 ( 0.0Y.I { 0. 07.) I 0.07.) ( o.o:o I II '
1.17.1
I
SENSATION OF MAR1111t, GENERAL I 0 2 1 0 0 0 I I 2
I 0.0Y.J 2.JY,J 1.llO I 0 .OY.l ( 0.07.) ( o.o;o I I c Z.37.l
'
(
I
FATIGIJE/WEAkN£SS I 7 10 5 5 4 J I • 16
e. v.1 I 11.47.I ( 5,7;0 I 5.87.) ( 4.6)0 ( :s. s:o I C 18.27.l
HEADACHE I 3 4 2 2 2 l 9
I 2.37.I 2.3)0 f 1.27.1 I 10.2::0
4.57.J 2 . 37.1
'
J.67.J ( (
UGHTlfEAOUI I 1 I 0 a 0 0 0 l
1.27.1 I I o.o:o o.or., o.o:n o.o;o ( o.o;o ( 1.UO
PAIN I 0
I
I 1
' 0
I
0
' . 0 D 1
0.0Y.I I I 1.1:1.1 o.o:o 0. 07. I ( 0. Cl¼ I ( o. 07.1 ( 1. lY. I
'
(
I
INFECTIOUS SYHDROf1[S I 0 I 0 l 0 0 0 l
0. 07. I I C 0.0)0 C l,lY.I C o.o:o C 0.07.) I o.ox, C 1.17.1
I
HERPES LAftIALIS, R~CURREHT I 0 I 0 l 0 0 0 1
0.DY. I I 0.0Y.) l .lY.I 0.07.1 0.0X I ( 0. 07.1 1.lXI
' C
C ( ( C
0
0
'-"
.0
~
Table 3 (oont.)
PATIEHT COlffl CLINICAL COt1PllIHTS
STUDY I 0894
TREATMENT
lOT IM1t!ER Ct12St
DOSE 20.r,o;
- --------------------------------------------------------------------------------------------------------------
I TOTAL VlCClHEES ( 88 PATIENTS) - DOSE l I
•----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUNSER
CLIHICll
l----------------------------------------------------------------------------1 MITH
COIIPllIHTS I O I 1 I ' t
..............................••...•..........•..........•.......... I 3
, I 4
....................... I 5 •
,
..........•.......... ,ICOttPLAJIITS
..........
IHTEGUMENTARY SYSTEM 0 0 0 0 0 l l
o.o:o 0.07.) 0.0iO 0. OY. J 0.07.) 1.27.1 l.lY.I
RASH, HOS 0 0 0 0 0 l l
O.OiO o.o;o o.o;o 0. O?. I o.o;o 1.2)0 1.lY.l
11\JSCULOSKELHAL 2 6 4 4 t 3 9
2.41.) 6.87.) 4.6if.J 4,7)0 Z.37.1 3.5if.) 10.21.)
lRTHRllGIA !OTHER) l 5 3 3 l 2 8
1.27.) 5.7¼1 3.41.1 3.5?.I 1.17.) 2. 37.1 9.17.1
MYOSITIS l 1 ~ l 1 1 1
1.21.) l,llO l.UO l. t?. J 1.17. I 1. 27.1 1.lY.I
DIGESTIVE SYSTEH l 5 6 z 0 1 10
1.21.) s.1;0 6.9if.l Z. 37.) o.o:o 1.27.) ll.4if.J
ASOOMINAl PllH!J/CRAMPS 0 1 0 0 0 0 1
o.o:o 1.17.) 0.0:r.1 o.o:o 0 . 07.1 0.07.l l.lY.I
DIARRHEA 0 3 t 0 0 0 3
0.01.J 3.47.) t.3if.l o.o:o 0.07.1 0.07. J 3.4)0
NAUSEA 1 z 3 2 a 1 6
1, 27. J 2,37.J 3.4if.) 2. 37.) 0.0)0 1,2Y.l 6.8i0
VOHITING 0 1 z 1 0 0 2
0.07.J 1.17.1 2.3%) 1. ZZ I 0.07.1 0.07.) 2. 31.t
omER 0 0 1 I o 0 0 1
0. 07.) 0 .07.J 1.1x1 I 1 0.0:r.1 o. 07.) 0 .07. J I _ 1.17.1
PSYCHIATI!IC/BEHlVI°"Al t 1 l l 0 0 z
t .47.) 1.17.1 l.17.1 1.27.) o.o;o 0.07.) 2.3i0
EMOTiotlAl llBILITY 1 l l l 0 0 l
1.21.) 1.17.) l.lif.l 1.27.) 0.07.1 0 .07. J 1.17.)
0
0
\II
-0
111
Table 3 (cont.)
PATIENT COUHT CLINICAL CONPLAIHTS
STUOY I 01194
TI!UTMENT
LOT NUl19ER Cl"l252
DOSE 20 }0:.
I TOTAL VACCINEES I && PATIENTSJ - DOSE 1 I

1----------------------------------------------------------------------------I
CLINICAL
COMPLAINTIJ
1----------------------------------------------•-----------------------------•
I 0 I 1 • 2 • :S I 4 I 5 I MITH
ICOMPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••••••••••••••••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
Il!IHTABILITY I 1 • 0 I 0 I O • 0 I O I I l
I I 1.21.1 I I 0.01.1 I c 0.01.1 I I 0.01.1 • I 0.01.1 I I 1.01.1 I I , 1.17.1
-----------------------------------1----------l-------·-·1·····-----l----------t---·--·---t----------l----------l-----------
PERSON!I MITH COttPUIHTS . I 31 I 33 I ti I U I II I II I I 54
I I l6.9i0 I I 37,57.J I I 24,17.J I I l't.0XI I I 9.21.l I I 9.JXI I I I 61.41.1
-----------------------------------1----------t----------l----------l----------l----------l----------l----------l-----------
PERSONs WITH NO c011PL AINTS I 5:S I 55 I 66 I 74 I 79 I 111 I I 34
I I n.11.1 I 1 62 . s1.1 I 1 75.97.1 I t et>.01.J I , 90.117.J I 1 91. 7;0 I I 1 311.67.J
----------------·--···-------------l----------1··-····-··1-····-·---t-------•--l----------l-·--------1----------1
PERscHS MJTH HO DATA I 1 I O I 1 I 1 I 1 I Z I I·····------
0
I I 1.21.1 • C 0.0X) I C 1.11.1 I C 1.uo I I 1.17.) I I t.3)0 I I I a.ax,
0
0
Ill
"'
(I'-
-
Table 3 (cont.)
PATIENT COUNT CLINICAL CotfPLAINTS
STUDY 089to
TREATMENT
LOT HUl1BER Ct1~52
DOSE 20M:'(;
I TOTAL VACCIHEES I 70 PATIENTS I - DOSE 2 I

1----------------------------------------------------------------------------I
I DAYS POST VlCCINATlON I tM18ER
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------1
I D I l I 2 I 3 I 4 I 5 •
NITH
ICOMPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••I••~•••••••
I I I I I I I I
REACTION, LOCAL UHJECT. SITEI I 20 I 13 I 3 I 2 I l I o I I 24
I , 30.31.1 I , 19.41.1 I c 4.5%1 I , 1.01.1 I , 1.57.1 I I 0.01.1 I I ( 35.lliO
-----------------------------------1----------1----------1----------•----------1----------1----------1----------•-----------
SORENESS I 2D I 13 I 3 I 2 I o I o I I 23
I , 10. 3Y. I I , 19. 47.1 I , ,. . s1., • , 1. 01. 1 I c a. ar.1 • , o. 01.1 • I , 34. 11.,
• I I I • I I I
HEMATCl1A I 1 I O • 0 I O • l • O • • 2
I l 1.57.) I l 0.0%) I l 0.07.1 • l 0.0Y.) • ( 1.57.) I l 0.07.1 • • I 3.0Y.I
-----------------------------------l----------l----------l----------1·---------1----------l----------•----------•-----------
sYsn:t11c I 7 I 10 I 6 I 7 I 6 I 6 • I 17
I C 10.67.1 I I lto.97.I I I 9.llO • l 10.4%1 I I 9.llO I l 9.17.1 I • I 25.<tiO
----------------------------------------------------------------------------------------------------------------------------
NHOLE BODY/GENERAL I 3
I
I 5 5 I• 5 I ,. 4 I 10
4.57.J I 1 7 .57.) ( 7.67.> I 1 7.5lO I C 6.17.1 ( 6.llO I • C 14.9%1
I I I
FATIGU£/WEAkN£SS I 2 I 5 5 I 5 I 4 4 • 9
3.0Y.I I l 7.57.) ( 7.67.J I l 7.5%) • l 6.UO 6.17.1 •I C 13.4% >
H!ADAOtE I 1 I• a 0
I
I a •I a
' 0
I
I 1
1.s;o I , o.o;o C 0.01.1 I , o.o;o I, 0.07.) ( 0.01.1 I ( 1.5?.I
I I I I
IHrECTIOUS SYtlDROMES I 0 1 a 0 I 0 0 l
0.0lO • 0.0iO I C o. or., o.ox, •I ( 1.5?.I
0.0%1 1.sr.1 • I
'
( (
I
HERPES GEHITALIS, RECURRENT I a 1 0 I 0 •I a 0 •I 1
I c a.or., I 1.5?.I
' O.OiO I 1.5lO ( 0.0:10 • 1
I •
o.ox,
I
(
( 0.01.1
'
IHTEGtl1ENTARY SYSTEN I 0 0 0 0 I 1 1 I I 1
0.0%) o.o:o o.oio I l o. 01.1 I 1 1.s:r.1 I I I 1.5iO
RASH, HOS I
' 0
' 0
' 0
I
I 0
I
I
1.s:o • ,
1
I
I 1
I
•I l
0.07.1 0.07.1 ( 0.01.1 I I 1.SiO • l I.SY.I I• I I 1.5)0
'
( o.a:o • 1
RESPIRATORY 0 a 1 • 1 •I 0 •I 0 • •I l
• O.OiO 0.0%1 l.5%1 • I • 1.57.I I l 0.01.1 Il 0.07.I •
• I I I.SY.I
'
(
'
0
0
U1
-0
.....
Table 3 (cont.)
PATIENT COUNT CLINICAL COttPllINTS
STUDY 08~
TRUTl1EHT
LOT WfflER Ct1t52
DOSE
20 K.'G
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIHEES I 70 PATIENTS I • DOSE 2 I
1----------------------------------------------------------------------------t
I DAYS POST VACCINATION I Nl,'19ER
CLINICAL
COMPLAINTS
l----------------------·•••--------------------------------------------------1
I O I 1 I 2 I 3 I 4 I 5 I
WITH
ICot1PUINTS
- ------- ---------- - -------- -- ------ i •••••••••• i ••••• .. ••••i ••••••••••I••........................aI ••11•••a• .. •l•••o•••w1HI
---••~•••••I••••••••••
PHARYNGITIS I SORE THROAT> 0 0 1 1 0 0 l
o.o:o ( o.o;n 1.s:o ( 1.s:o ( 0.0;1.1 ( 0.0?.I ( 1.s:o
l'IUSCULOSKELETAL 2 2 0 1 0 0 ~
3.o:o ( 'J.DXJ 0 .07.1 ( 1.51.l ( 0.01.1 ( 0.0?.I ( 6.0)0
ARTHRALGIA, t10HOARTICULAR l l 0 0 0 0 l
1.s:o ( 1 .57.1 ,.o:o ( 0. 07.J ( o.o:o ( o.o;o ( l.SY.l
ARTHRALGIA !OTHER) l l 0 0 0 0 2
1.SXI ( 1.SXI 11.07.) ( 0. 07.) ( o.o;o ( 0.0?.I ( 3.0Y.)
tlYALGIA 0 0 0 1 0 0 I 1
o.o:o ( II.DY.I 0.0?.I ( l. 57.l ( o.ox, ( 0.07.) I c l.SY.l
DIGESTIVE SYSTEM I t I l O O O O 3
:S.0i() I I 1.s:o I 0.07.) I 0.07.) ( 0.07.1 I o.o;o C 4.SY.J
NAUSEA I 2 0 O O 0 0 2
l.0Y.J ( 0.0XI C 0.0?.I I D.0lO ( 0.07.l I 0.0:1.1 I 3 . 0Y.I
LOOSE STOOL I O 1 D O o O l
O.0Y.J ( I.SY.I ( 0.0:t.l I 0.07.l ( 0.07.J I o.o;o I l.SX)
PS'f'CHUTRIC/BEHAVIORAL I 1 l l l l I l
1.5.r.1 c 1.51.J c 1.5:0 1 1.57.J c 1.57.1 1 1.s:1.1 , 1.si1
INS~IA/OISTUR6EO SLEEP I 1 l l l l l l
I C l.Sll I 1.51.1 C 1.5?.I C 1.S?.I ( I.SY.I ( 1.5Y.I ( l.SiO
-----------------------------------t----------l----------l----------1----------1----------1----------I----------I-----------
PERSOHS WITH COl1PLA1NTS I n I U I '> I 9 I 7 I 6 I I 34
I c ltt.e:o I c 31.31.1 I C lJ.6:1.1 I I l'J.4Y.I I I 10.67.I I I ,.17.l I I I 50. 7%1
-----------------------------------t----------t----------l----------l----------1----------1----------1----------I--
PERSOHS WIT1' NO COMPLAINTS I '+3 I ~6 I 57 I 511 I 5'> I 60 I I
._______
33
_
I C 65.21:1 I < 66.7lO I c 66.4:t.l I c 6&.6Y.I I t 69.47.1 I 1 90.9%1 I I 1 49.3%1
-----------------------------------1----------l----------l----------t----------l----------l----------l----------l-----------
PERsoNS WJTil NO DATA I l I l I l I 1 I l I l I I l
I ( 1.5%1 I C 1.5%) I ( 1.5%1 I C 1.5iO I ( l.5)O I f l.5iO I I I 1.5%1 0
0
\II
-4
OIi
Table 4
PATIENT COUNT "AXIHUN 'TIEHPERA~ES
STUDY I 0894
TRUTt1EHT
LOT N\JMBER I CHZSZ
DOSE 20 M:G
I TOTAL VACCIHEES I M PATJEHTSI - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCJHATIOH I HU'19ER
HAX TEHPERATVR,
I DEG F, OIULI
1---------------------------------------------------------------------------------------I
I O I 1 I Z I l I 4 I 5 I I
WITH
I HA)( TEHP
••••••••••••••••••••••-•••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l•••••--•••l••••••••••I••••••••••
NORHAL I 1 I l I 3 I 4 I 4 I I 2
I I 1. 1r. t I c l.6r.1 I , 3.T/.1 I ( 5.or.t I 1 4.97.J I I "
5.0lOI I• I 2.4iO
I I I I I I I I
< 99 I 62 I 70 I 67 I 66 I 70 I 70 I I 56
80.5)() I I 84.37.1 I I &1.7Y.I I I ez.s;o I ( 86.4)0 I I 87.SlO I I I 66. 7Y. I
I I I I I I I
99 - 99.9 I 14 I 10 I 11 I 9 I 6 I 4 I I 24
1e.2r.1 I c lZ.07.l I I 13.47.1 I I 11.27.J I C 7.47.l I 1 s.o;o I I c 28.6)0
lOD - 100.9 I o I o I l • 1 I 1 I 2 I I z
I I o,or., I c o.or., I 1 1.2;0 I 1 1.2r.1 I c 1,2;0 I 1 2.s,o I I c 2,4;0
------------------------1----------l----------l----------l----------l----------l----------l---------------------1-----------
TE11PERATURE TAKEH I 11 I n I ez I eo I e1 I eo I I M
I 1 &7,57.J I 1 ,,.,37.J I , ,1.2;0 I c ,o.97.1 I 1 ,2.0:0 I c ,o.,;o I I 1 ,s.sr.,
------------------------l----------1----------1----------I----------I----------I----------I---------------------I-----------
TEt1PERATURE HOT TAKEN I 11 I s I 6 I e I 1 I e I I "
I I 12.SiO I I 5.71.1 I l 6.0Y.I I C •• 17.J I ( &.07.) I I ,.un I I C 't.5i:J
0
0
\II
-c
-0
Table 4 (cont.)
PATIENT COIJtT NAXIl'1Ul1 TEHPERATURES
STUDY 0894
TREAfflENT
LOT NU1BER CM:!52
DOSE
20 MXi
·------- ' TOTAL VACCINEES I 70 PATIENTS! - DOSE 2 I
1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION • NU1111ER
HAX TEHPERATUR!
(DEG F , OR AL I
•-----------------
I O I l
---- -------------------------------------------------------------
I 2 • J • 4 • 5 I • -----•• Nl WITH
X UHP
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••••••••••••• l•••••••••• I••••••••••
I I I I I • • •
NORHAL • J I 4 I 3 I 4 • la • la I • 2
• ( 4.8i0 I ( 6 . 2:0 • I 4.6)()I ( 6 . 3)(1 • I 6.llO • ( 6.lZI • • I l. OY. I
< 99 I• Sit I• 57 I• 57 •• 56 II 56 •• 55 •• •• 52
• 1 a1.1z, I 1 &1.11.1 • , e1.n, I I e1.5:o I I e1.sz1 • 1 es.,,o I • 1 77 . 6Y.I
I I I • I I I I
99 - n. 9 • s I 4 I s I 4 I tt I s I • n
I I 8.1)( ) I I 6.2Y.I I ( 7.7;1,) I I 6 . 3;1,I I ( 6.JlO I ( 7 . 87.1 I • C l9.4Y.I
------------------------•----------l----------
TE11PERA1URE TAKEN • 62 I 65
l----------l----------l----------•----------l---------------------1-----------
I 65 I M I 6ft • M • • 67
• 1 ae.6:o I 1 92.91. I I 1 ,2.•io I I n.4i> I r n.•i> • , •1.tii1 • • c ,s.n,
------------------------•----------l----------
n:HPERATURE NOT TAKEN • e I s •
l----------l----------
s I ,
l----------1----------1---------------------l-----------
I , I • I I 1
I I 11.lt)O • I 7 . UO I I 7.llO I ( 8.6X) I I 8 .6l0 • I 8 .6:t.l I I I 4.3)0
0
0
0-
0
0
co
0\
co
►
C
....
:::>
VI
00601
PROTOCOL: Alum-Adsorbed Yeast Recombinant Hepatitis 8 Vaccine,

Study 898.
PURPOSE: To evaluate antibody and clinical responses of

1nitially seronegative healthy adults to 10 and 20 mcg
injections of yeast recombinant hepatitis B vaccine.

Lot #85860/22123/C-M125 (20 mcg HBsAg/ml)
Lot #85861/22124/C-Ml26 (10 mcg HBsAg/ml)
PRINCIPAL Robert Bishop, M.D.

WPJB-4
SECONDARY E. P. Avencena, M.D.

WP38-4
STUDY Merck Sharp and Dohme

LOCATION: West Po1nt, PA 19486
DATE INITIATED: November 18, 1985

employees of Merck & Co., Inc. of e1ther sex
(excluding pregnant women) who are 40 years of age or
older, are negative for HBsAg, ant1-HBt, and ant1-H8s,
have a normal ALT level and have not previously
received any hepatitis 8 vaccine.
30011/1
12/31 /85
00602
-2-
STUOY PROCEDURE Eligible participants receive a 1.0 111 (10 mcg or 20

mcg HBsAg) intramuscular injection of vaccine in the
deltoid muscle on day 0, and at l and 6 months.
Vaccine recipients are ask~ to record their
temperature daily for f1ve days after each injection
of the vaccine and also to record any local or
systemic complaints that they may have during this
period.
participant 1-2 weeks before the first injection of
vaccine is given. Post-vaccination blood samples are
taken at 1, 2, 3, 6, and 8 months following the first
injectiQn from all vaccine recipients and at 12 and 24
months from those who deve 1op ant 1body by 8 months.
All samples will be tested for HBsAg, anti-HBc, and
anti-Hes. The prevaccination santple and the two month
post-vaccination sample will also be tested for ALT.
Subjects who fail to develop antibody following three
injections of vaccine and those who have a trans tent
ant 1body response that becomes negative by 12 months
after the first injection may receive a fourth
injection of vaccine. An additional blood sample will
be taken one 110nth after the fourth injection of
vaccine.
RESULTS: One person has received a single 10 11eg injection of

vaccine, while two persons have received single 20 mcg
injections of vaccine. None had any complaints.
Post-vaccination serologic results are not yet
available.
30011-2
12/31 /85
00b03

Study 900.
vaccine among healthy male homosexuals who are
negative for hepatitis B virus serologic markers .

lot #858&1/22124/CM126 (10 mcg HBsAg/ml)
PRINCIPAL Arie J. Zuckerman, M.O.

INVESTIGATORS: Professor of Microbiology
Director, Department of ~edical Microbiology
London School of Hygiene and Tropical Medicine
Keppel Street
London WCl[ 7HT
United Kfogdo111
lain Murray-Lyon, M.D.
London W.6.
United Kingdom
SECONDARY Or. John Coleman
INVESTIGATORS: Charing Cross Hospital
London W.6.
United Kingdom
Or. Michael Anderson
London W.6.
United Kingdom
STUDY LOCATION: Charing Cross Hospital

London W.6.
United Kingdom
DATE INITIATED: August 1985.


healthy male homosexuals who are negative for HBsAg,
anti-HBc and anti-HBs, and have not previously
31061/1
12/31 /85
00604
Study 900
PROCEDURE: Prior to enrollment in the study, all prospective

participants w111 receive a full medical examination .
Any evidence of possible immune deficiency wi 11
eliminate a candidate from receiving vaccine. A blood
sample wil 1 also be obtained prior to vaccination and
assayed for hepatitis 8 serolog1c markers and for
antibodies to HTLV III.
Eligible participants will receive a 1.0 ml injection
of vaccine in the deltoid muscle at 0, 1, and 6
fuonths. Study participants will be asked to take and
record their temperatures for five days after each
systemic co11plaints that they may have. They wi 11 be
asked to notify the study physician inmediately if any
unexpected or serious reaction occurs.
follow-up blood samples will be obtained at 1, 2, 3,

6, 8, 12, and 24 months following the first injection
of vaccine. All samples will be assayed for HBsAg,
anti-HBc and anti-HBs. The 12 and 24 month samples
will also be tested for antibodies to HTLV III.
Assays will be performed 1n Dr. zuckernian's
laboratory. In addition, samples may be assayed for
yeast antibodies and anti-HBs subtype specificity by
MSORL.
Subjects who fail to develop anti-HBs following three

doses of vaccine (nonresponders) and those who have a
transient antibody response (transient responders)
that becomes negative by 12 months after the first
dose, may receive a fourth injection of vaccine. An
additional blood sa~ple will be taken one month after
the fourth dose.
A complete physical examination will be repeated at&,

12, and 24 months.
RESULTS: Serologic and clinical follow-up data are not

currently available. No serious or alarming adverse
3106 I/2
12/31 /85
STUDY 904
OObOS
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepatitis B vaccine,

Study 904
PURPOSE: To evaluate clinical and antibody responses among

initially seronegat1ve healthy adults 20 years of age
or older to - 10 mcg doses of yeast recombinant
hepatitis 8 vaccine

Lot #89426/22930/C-14178 (10 mcg HBsAg/0.5 ml)
Lot #81991D/18068/C-L217 (10 mcg HBsAg/0.5 ml)
PRIMARY Harold A. Kessler, M.D.

INVESTIGATOR: Assistant · Professor of Medicine and
Inmunology/Microbiology
Rush-Presbyterian-St. Luke's Medical Center
1753 west Congress Parkway
Chicago, IL 60612
SECONDARY Constance Ann Benson. M.O.

INVESTIGATORS: Rush-Presbyterian-St. Luke's Medical Center
1753 West Congress Parkway
Chicago, IL 60612
Alan A. Harris. M.D.
Rush-Presbyterian-St. Luke's Medical Center
Chicago, IL 60612
STUDY LOCATION: Rush-Presbyterian-St. Luke's Medical Center

Chicago, IL 60612
DATE INITIATED: October, 1985
31161-1
1/2/86
00&06
Study 904
STUDY POPULATION: The study population will consist of approximately

100 healthy adults of either sex (excluding pregnant
women) who are 20 years of age or older, are negative
for HBsAg, anti-HBc and ant1-HBs , have a normal ALT
level, and have not previously received any hepatitis
B vaccine.
PROCEOURE: Participants will be assigned to one of two groups as

defined below:
Number of Dose Volume
Group Pa rt i c1 pants ___va...c"""c__i __
ne"'-"L=o.;:;.t__ CHBsAg)
l 50 89426/22930/C-~718 0.5 ml (10 mcg)
2 50 81991D/18068/C-L217 0.5 ml (10 mcg)
Participation in either group l or 2 wi 11 be
determined by a randomization schedule provided by
Merck Sharp & Oohme.
Eligible participants receive a 0.5 ml injection of
vaccine in the deltoid muscle at 0, 1, and 6 months.
Study subjects are asked to take and record their
temperatures for five days after each injection of
vaccine and to record any local or systemic complaints.
A blood sample will be obtained at 1-2 weeks prior to
the f1 rst injection of vaccine. Post-vaccination
blood samples (10-15 1111) will be obtained at 1, 2, 3,
6, and 8 months following the first dose of vaccine
from all vacc1nees and at 12 and 24 months from those
who have developed antibody by 8 months. All samples
will be tested for HBsAg, anti-HBc, and antf-HBs. The
sample taken 2 months after the first dose of vaccine
will also be tested for ALT.
Subjects who fail to develop antibody following three
doses of vaccine (nonresponders) and those who have a
transient antibody response (transient responders)
that becomes negative by 12 months after the first
dose , may receive a fourth dose of vaccine. An
additional blood sample will be taken one month after
the fourth dose.
Sera may also be assayed for yeast antibodies and
anti-HBs subtype specificity.
All assays will be done at Rush-Presbyterian-
St. Luke 1 s Medical Center.
31161-2
1/2/86
00607
Study 904
RESULTS: HEALTHY AOUL TS:
10 mcg Lot #89426/22930/C-M178 at 0, 1, and 6 months

10 mcg Lot 81991D/18068/C-L217 at 0, l, and 6 months
1. Number Vacci nated:
Injection No.
___L_ ......L. -L
Lot C-Ml 78 50 50 0
Lot C-L217 50 50 0
Serologic data are not yet available.
No serious or alanning advierse experiences have
been reported.
31161-3
1 /2/86
00608
PROGRAJ:l: Yeast Recombinant Hepatitis 8 Vaccine, Study 907

doses of yeast recombinant hepatitis 8 vaccine
follo~1ng intramuscular or subcutaneous administration.
VACCil\lE: Yeast Recombinant Hepatitis B Vaccine Lot C-L215

(10 mcg HBsAg/0.5 ml)
PRIMARY Shiro Iino, ~.D.

INVESTIGATOR: First Department of Internal Medicine
Faculty of Nedicine, University of Tokyo
Hongo, Bunkyo-ku, Tokyo
Japan
Tetsuo Kuroki, M.D.
Third Department of Internal Medicine
Medical School, Osaka City University
Asahi-cho, Abeno-ku, Osaka
Japan
SECONDARY Takeyuki Monna, M.D.

INVESTIGATORS: Professor
Department of Public Health
Medical School, Osaka City Univen+ty
Hiroko Oka, ".D.
Third Department of Internal Medicine
Medical School, Osaka City University
Japan
STUDY LOCATION: Tokyo and Osaka

Japan
DATE INITIATED: May 7, 1985
STUDY POPULATION: Number of

Population Subjects Regimen
Healthy adults 124 10 mcg (0.5 ml) at
0, 1, and 6 months
I.M. or S.C.
31131-1
l /17/86
00609
Study 907
PROC£DURE: Parttctpants received intramuscular o r subcutaneous

injections of vaccine according to the regi111en
outl tned above under STUDY POPULATION. Participants
were asked to record their temperature daily for three
days after each injection and to note any local or
systemic complaints.
Serum sa,ap les were obtained before vaccination.

Follow- up blood specimens have been or will be
obtained 1, 2, 4, 6 , 7, 9 and 12 rROnths after the
initial dose of vaccine. Serum samples have been or
will be assayed for HBsAg, anti-HBs , anti-HBc and
c: a u,111>,-2) l\i·h-r hh')ratory examinations by the
/h \{/b..1.}\ { } Samples may also be assayed at
the ------.c--= 4 for yeast antibody.
RESULTS: 1. Number Vaccinated:
Injection No.
1 -1... ...L
ffi 124 121
The ant1-HBs seroconversion proportions were 28%

(16/57) and 281 (17/61) at one month after the
first dose, 93% (52/5&) and 87% (53/61) at 6
months and 98% (54/55) and 97% (56/58) at 7 months
with intramuscular and subcutaneous injections.
respectively.
Route of Type of Frequency in \ by Injection tto.

Iniectiqn Colplaints _J_ _l_ _3_
I. Fl . Injection 19.4' 11. 31,

*
Site (12/62) (7/62)
Syst• k 9.1' 14 .5'

(6/62) (9/62)
s.c. Injection 16.11' 11.3'

*
Site (10/62) (7162)
Systellic 16. 1, 8. lf, ...

(10/62) (5/62)

attributed to vaccination.
* not yet analyzed

31131-2
1 /17/86
00610
Study 907
RESULTS: (Contd) TABLE 1
Antibody Responses Among Healthy Adults

Following Vaccination w1th 10 mcg Doses of
Recombinant Vaccine Lot C-L215 at O. 1 1 and 6 ~onths
RIA
Cut-Off
Index
<2. 1 57 61 41 44 13 18 6 10 4 8 2
2 .1- 21 14 16 31 38 24 30 25
------
36 0 1
21-103 2 1 12 5 . 26 20 25 16 6 12
105-208 1 1 1 2 1 31 32
100- 17 5
Seroconvers1on % 28.1 27.9 77.2 70.1 89.5 83.6 92.9 86.9 98.2 96.6
31131-3
1/17/86
STUDY 912
0061 l
PROGRAf.1: Yeast Recombinant Hepatitis B Vaccine, Study 912

doses of yeast recombinant hepatitis B vaccine
following intramuscular or subcutaneous administration.
VACCDIE: Yeast Recombinant Hepatitis B Vaccine Lot C-L220

(10 mcg HBsAg/0.5 ml)
PRIMARY Tatsuo Shimizu, M.O.

INVESTIGATORS: Director
Division of Internal Medicine
Osaka Red Cross Hospital
Fudegasaki-machi, Tennoji-ku, Osaka
Japan
Masahiro Nakao, M.D.
Director
Shirokita Municipal Hospital
Takadono, Asahi-ku, Osaka
Japan
Toshiaki Marumo, M.D.
Director
sum1yosh1 Mun1c1pal Hospital
Higash1-Kagaya, Suminoe-ku, Osaka
Japan
Yuriko Tsubakio, M.D.
Division of Pediatrics
Osaka Municipal Mothers' and Children's Hospital
tneminami, Nishinari-ku, Osaka
. Japan
Yuichi Kobayashi, M.O.
Director
Domyoji Municipal Hospital
Oomyoj i, Fuj iidera
Japan
Tomohiro Kurahori, M.O.
01 rector
Ashiya Municipal Hospital
Asahigaoka-machi, Ashiya
Japan
31141-1
1/17/86
00612
Study 912
PRIMARY Akio Todo, Pll.D.

INVESTIGATORS: Director
(Contd) Division of Internal Medicine
Kobe Central Municipal Hospital
inatojima-machi, Chuo-ku, Kobe
Japan
SECONDARY Seigo Takamatsu, M.D.

INVESTIGATORS: Division of Internal Medicine
Osaka Red Cross Hospital
Masayoshi Fujisawa, M.D.
Sumiyoshi Municipal Hospital
Fumiaki Ohnishi, M.D.
Domyoj1 Municipal Hospital
Dr. Tetsuzo Koda, M.D.
Ash1ya Municipal Hospital
Or. Eiji Komori, M.D.
Kobe Central Municipal Hospital
STUDY LOCATION: Osaka, Domyoji, Ash1ya and Kobe
Japan
DATE INITIATED: September 2, 1985
STUDY POPULA TIO Number of

Population Subjects Regimen
Healthy health 175 10 mcg {0.5 ml) at
care personne 1 0, 1, and 6 months
I.t4. or S.C.
31141-2
1/17/86
00&13
Study 912
PROCEDURE: Participants received intramuscular or subcutaneous

injections of vaccine according to the regimen outlined
above under STUDY POPULATION. Participants were asked to
record their 'temperature daily for three days after each
injection and to note any local or systemic complaints.
Serum samples were obtained before vaccination. Follow-
up blood specimens have been or will be obtained 1, 2, 4,
6, 7, 9 and 12 months after the initial dose of vaccine.
Serum samples have been or will be assayed for HBsAg,
antt-HBs , anti-HBc a_nd several other laboratory exami-
nations by the (b) (4) Samples may also be
assayed at the ..___.:-.... --------for yeast antibody.
RESULTS: 1. Number Vaccinated:

In1ection Number
1 2 3
124 124 -;r
* not yet vaccinated
The anti-HBs seroconversion proportions were 45%
(38/84) and 22% (19/85) at one month after the first
dose and 75% ( 56/75) and 59% ( 43/83) at one month
after the second dose with intramuscular and
subcutaneous injections, respectively.
3. Clinical Co!!!2laints:
Route of Type of Freguencll in % bi Injection No.
Injection Com'1laints 1 2 3
l. M. Injection 3.41 0%
Site (3/87) (0/85)
Systemic 23.0I 10.6%
( 20/87) (9/85)
s.c. Injection 6.81 9. 1%

Site (6/88) ( 9/88)
Systemic 27.3% 12. 5%

(24/88) ( 11 /88)

attributed to vaccination.
31141-3
1/17/86
00614
Study 912
RESULTS: (Contd) TABLE T
Antibody Responses Among Healthy Adults

Following Vaccination with 10 mcg Doses of
Recombinant Vaccine Lot C-l220 at O and 1 Month
RIA Anti-HBs Resoonse tS/Nl
Cut-Off Before l mo. 2 mos.
Index 1.M. S.C. I.JII. S.C. I. rs'! . ~
<2.1 84 85 46 r,r, 19 30
2. 1- 21 39 18 36 32
21-103 g l 19 11
105-208 l
100-
Seroconversion % 45.2 22.4 74.7 58.9
3114!-4
l /17/86
STUDY 914
00b15

Study 914

for hepatitis B virus serolog1c markers.

Lot #85861/22124/C-Ml26 (10 mcg HBsAg/ml)
PRUIIARY Alain Burette, M.D.

INVESTIGATORS: venue l' Echev1nage
19-1180 Bruxelles
Belgiu,
Michel Deltenre, M.D.
rue des Hippocampes
20-1080 Bruxelles
Belgium
STUDY LOCATION: Hospital Brugman

Bruxelles
Belgium
STUDY POPULATION:· The study population will consist of approximately 20

health care personnel of either sex (excluding
pregnant women) who are negative for HBsAg, ant1-HBc
and ant 1-H8s. have a nonna 1 ALT level and have not

injection of vaccine into the deltoid muscle at o. 1,
and 6 months. Study participants are asked to take
and record their temperatures for five days after each
systemic complaints. They are also asked to notify
the study physician irnnediately if any unexpected or
serious reaction occurs.
31151-1
1/2/86
00616
Study 914
PROCEOURE: (Contd) A blood sample (10-15 ml) will be obtained from each
participant approximately 2 weeks prior to the first
injection of vaccine. Follow-up blood samples will be
obtained at 1 , 2, 3, 6, and 8 months following the
first injection of vaccine from al 1 vaccinees and at
12 and 24 months from those who have developed
antibody by 8 months. All serum samples will be
tested for HBsAg , Ant 1-HBc and ant i-HBs . The 2 month
post-vaccination sample will also be tested for ALT.
If any subject experiences clinical symptoms
compatible with hepatitis, blood samples drawn at that
time will also be tested for ALT.
Subjects who fai 1 to develop antibody fol lowing three

doses of vaccine and those who have only a transient
antibody response that becomes negative by 12 months
after the first dose may rece1 ve a fourth dose of
vaccine. An additional blood sample will be taken one
month after the fourth dose.
Assays for HBsAg, anti-HBs and ant1-H8c on the

pre-vaccination serum samples and all ALT assays will
be perfomed 1n Belgium. The Me rck Sharp & Oohme
Research Laboratories in West Point, Pennsylvania wi 11
perform post-vaccination assays for HBsAg, anti-HBc,
and anti-HBs. Assays also 111ay be done for yeast
antibodies and ant1-HBs subtype specificity.
10 mcg Lot #85861/22124/C~126 at 0, 1, and 6 months
Injection No.
Dose Level _,_ _l_ _3_
10 mcg 20 20 0
Serologic data are not yet available.

However, the study investigator states that no
local or general sign of intolerance has been
observed. The study continues in pr ogress.
31151-2
1/2/8&
HEALTHY TEENAGERS
00617
SUMMARY - HEALTHY TEENAGERS
To date, 165 healthy male teenagers, 15-20 years old, have been inmunized with
yeast recombinant hepatitis B vaccine. Antibody and clinical responses to 10, 5
and 2.5 mcg doses of the vaccine administered at 0, 1 and 6 months in the
deltoid muscle were evaluated in armed forces recruits who were negative for
hepatitis B markers. Fifty-five recruits received each dose level. The vaccine
was highly irm1unogenic and well tolerated in this population. Clinical
complaints were mild and transient. Protective levels of antibody (mIU/ml >10)
were induced 1n greater than 94% of vaccine recipients after 3 injectTons
regardless of dose level administered. Ninety-eight to lOOt of vaccine recipi-
ents developed protective levels of antibody after 2 inj~ctions of either 5 or
10 mcg doses of vaccine.
I11111unogenicity
Antibody to hepatitis B surface antigen was measured at 1, 3, 6, 7 and 12 months
postvaccination. At 7 months serologic data were available for 52, 54 and 53
vaccfnees who received 10. 5 and 2.5 mcg doses, respectively.The seroconversion
rate at 7 months was 100% for all dose levels when the cutoff was S/N >2.1.
When the cutoff was mIU/ml >10, the seroconversion rates were 100% for 5 and 10
mcg and 94% for 2.5 mcg. ~t 12 months, 100% of those who received 5 or 10 mcg
doses of vaccine continue to have protective levels of antibody, while 91%
(48/53) of those who received 2.5 mcg doses continue to have protective levels
of anti-BHs. Table 1 shows seroconversion rates for up to 12 months of
follow-up. A significant effect of log dose level on seroconversion rates was
seen at 3 months (p s 0.006) and 6 months (p = 0.030) when the cutoff was S/N
>2.1, although the minimum seroconversfon rates at these times were 91% and 94%,
respectively (see Appendix 1 for methods used in statistical analysis). When
the cutoff was mlU/ml >10 a significant effect was seen at 3 (p <0.001), 6 (p
<0.001) and 7 months (ps 0.033}. Seroconversion rates increased with log dose
level.
Statistical analysis showed that log titers increased significantly with dose
level at all time points ( p <0.01). Figure 1 illustrates this dose-response
relationship at 7 months. Geometric mean titers for all vaccinees at 7 months
were 3056.9 mIU/ml, 2553.4 mIU/ml and 846.3 mlU/ml for 10, 5 and 2.5 mcg doses,
respectively (Table 1). Figure 1 gives confidence intervals on the predicted
GMT at 7 months by dose in hea 1thy teenagers. At 12 months geometric mean
titers for all vaccinees ·were 583.1 mIU/ml, 498.1 mlU/ml and 324.7 mIU/ml for
10, 5 and 2.5 mcg doses respectively.
Safety
Clinical data fol lowing the first two injections of vaccine in 165 vaccinees
were available for statistical analysis. Clinical data following the third
injection in 164 vaccinees was sunmarized but not analyzed (Table 2). The
incidences of local {injection site) complaints, of systemic complaints, of
either local or systemic complaints, and of fever {oral temperature of l00°F or
more) were analyzed. The incidence following the first, second, or third
injection respectively, was defined as the number of subjects with the complaint
00618
at any time during the 5 day period following vaccination divided by the number
reporting while the total incidence was the sum of complaints over the three
injections divided by the number with follow-up. In general, the vaccine was
well tolerated in this population . Clinical complaints were mild and transient.
The incidences of local complaints, of systemic complaints, of either injection
site or systemic complaint, and of fever were evaluated as a function of log
dose level. No significant trend was found after the first or second injection.
Almost no fever was reported after either injection or at any dose level. The
only local complaint reported was soreness (13%) and the only systemic
complaints were malaise (6%) and headache (2%). The incidence of each complaint
tended to be lower after the second injection, Clinical complaints following
the third injection were minimal. The only complaint reported was injection
site soreness (2-6%).
Study 1819
Table 1
#lntlbody Responses Aimng Initially Seroneptive HNlthy Teenagers Following Vaccination with 10, 5, or 2.5 lll!C:9 Doses of
Yeast Aec:CJllbtnant Hepatitis Vaccine I lot 979/C-lt564 or lot 985/C-IC732 •t o. 1 and 6 ftanths in Study e1g
.- -- -- - .. . - -·
with
10 IIIC!IJ (Lot
Anti~s I
C-«564J
CIITl CalUflll 2 I I
5 ll!Cll {Lot t--1(732
vi tll Anti-49s
I I CIIT U/111
,nm I S/r.1?.
2.1
IIIIU/lill
~10
I All SIN >
YKclnees 2.1
I I alU/111
~ 10
I SIN?.
2.1
ldU/..1
1 ::,10
I All I
SIN > lldU/111
VaccinteS 2. 1 10
:!1_
SIN?,
2.1
mllJ/ml
::, 10
All
Vaccinees
Re~rs
s~~U/ml
2.1- !~ 10
I1 I 61(35/54) 39(21/54) 10. J 32.8 116.6 59(32154) 19(10/54) I 4.0 10.S I I

58.S S9(32/54) I 26(1~S4) I 4.3 9 . 901 24.5
i3 '100(53153) 95(51/53) 213.3 213.3 245.8 100(54154) 94(51/54) I 101.9 I 107.9 127.4 91(49/54) 67(36/S4) 23.J 31.8
'
63.3
I
!' 100(53153) 99(52/53) 199.0 199.0 211.0 IG0(54154) 100(5415') I IOU 101.S t01.S 94('9/SI) 1113'/SI) ! 2'.1 31.3 59.4
i7 1100(52/~) 100(52/52) , 3056. 9

I
3056.9, 3056.9
'
100(54/54) . 100(54154)
I
I
2553.3 2553.3 53.3 100(53153) 94(50/53) ~.3
I
· 846.3 1131.8
.
I 4!19.8 547. 1
'12 ' 100(54154) 100(W54) ; 583. 1 583.1 ; 583.1 100(54/54) 100(54154) ~ 498.1 _.).__ 498.1 _,_.4'9.1 __1_ 92(49/53) _ 91(48/53)__}24. J ...
'
24771/S
0
12/31185
-
0
0-
-0
FIOOR( 1
Confidence htervds on the Preclcled Mean at 7 Months

By Dose in Hedlhy Teenagers
Who Received Yeast Reco,1 .binant ~titis B Vaccine
Prepared t>v t11e I -; Method
IOl
. 2981
'L'
@)
·-
-+-
C ~ 1097
CD
en
C
0
Q. I- 403
Ill
4D
0::
...,_
0
ii ~ 148
>
,.
~
0
0
O-
2.5 Meg 5 Meg 10 Meg N
c:,
DOSE
00621
Table 2
Percent (Proportion) of Healthy Teenagers (Ages 15-20) with

Clinical Complaints During a 5-Day Period Following Vaccination
With Yeast Recombinant Hepatitis B Vaccine
Study 819
First Second Third

Ttee of Comelaint Injection InJection Injection Total
2.5 mcg of Vaccine
Local ( Injection Site)
Systemic
12.7 (7/55)
5.5 (3/55)
J.8
0 (0/55
o,ssl 1.9
0
(1/54)
(0/54~
I
4.8 8/164~
1.8 3/164
Any Local or Systemic 12.7 {7/55) 1.8 (1/55 1. 9 (l/54 4.8 ( 8/164)
Fever l,100° F (Oral) 0 (0/55) 0 {0/55) 0 (0/54) {O) { 0/164)
5 mcg of Vaccine
Local (Injection Site} 5.5 {3/55) 9.1 (5/55) 5.5 (3/55) 4.8 ( 8/165)
Systemic 3.6 (2/55) 3.6 (2/55) 0 (0/55) 2.4 ( 4/165)
Any Local or Systemic 9.1 (5/55) 9.1 (5/55) 5.5 (3/55) 6.1 ( 10/165)
Fever 1100° . F (Oral) 1.8 ( 1/55) 0 {0/55} 0 (0/55) 0.6 ( 1/165)
10 mcg of Vaccine
Local (Injection Site} 9.1 (5/55) 5.5 (3/55} 0 (0/55) 4.8 ( 8/165)
Systemic 5.5 (3/55) 0 {0/55) 0 (0/55) 1.8 ( 3/165)
Any Local or Systemic 12.7 (7/55) 5.5 (3/55) 0 (0/55) 6.1 (10/165)
Fever 1 l00°F (Oral) 0 (0/55) 0 (0/55) 0 (0/55) 0 ( 0/165)
OObZZ
A P P ENOI X l
S T AT I S T I CAL ME T H O D S
31241/11
1 /21 /8£>
00623
All tests of significance 1,1ere two-sided at 0.05 s;gnificance level.
A. Clinical Complaints
1. The incidence of the various clinical complaints in dialysis
patients on the three dose regimen, healthy teenagers and healthy
~antel-Haenszel Testl for trend .
2. All other differences in the incidences of the various clinfcal
complaints 1n dialysis patients due to don level or regimen and
in health care personnel rece;ving vaccine from consistency lots
8. Seroconversion Rates
1. The effect of dose level on seroconversion rates in healthy
adults, healthy teenagers and healthy children was analyzed over
studies using the Mantel Haenszel Testl for trend.
2. D1fferences in seroconversion rates in healthy adults due to age
or sex were evaluated over studies us;ng the Mantel Haenszel
3. Differences 1n seroconvers;on rates due to age in healthy
children, dose level in dialys1s patients, and vaccine lot in
Chi-Square.

The effect of age, sex, lot (consistency lots only in Study 880), or
dose level (all other studies) in health care_ personnel and other
age 1n healthy children, and of dose level and regimen in dialysis
antigen were assigned a titer of 0.3 mIU/ml in the analysis.
REFERENCE
1. Tarone RE, ware J: On Distribution-Free Tests for Equality of
Survival Distributions. Biometrika 64: 156-160, 1977.
3124{/12
-
en
co
...~
:::,
V,
PROGRA~: Yeast Recombinant Hepatitis B Vaccine, Study B19
PURPOSE: To compare antibody and clinical responses to 5 and 10

mcg doses of the vaccine among teenegers who are
negative for hepatitis B virus serologic markers.

Lot #979/C-K564 - 10 mcg HBsAg/~1
Lot #985/C-K732 - 5 mcg HBsAg/ml
PRIMARY George Papaevangelou, M.D.

INVESTIGATOR: Professor of Epidemiology &Medical Statistics
National Center for Viral Hepatitis
Athens School of Hygiene
P.O. Box 14085
Athens 11522, Greece
SECONDARY Charalambos Vissoulis, M.D.

I NVESTI GA TOR: Associate Professor of Medicine
University of Athens Medical School
47 Skoufa Street
Athens 10672, Greece
STUDY LOCATION: Greek Naval Base

Poros, Greece
DATE INITIATED: Hay 12, 1984
STUDY POPULATION; The study population consists of 165 teenagers (15 -

20 years of age) who are armed forces recruits, who
are negative for HBsAg, anti-HBc and anti-HBs, have a
normal ALT level and have not previously recehed any
24771/1
l /15/86
00&25
Study 819
PROCEDURE: Eligible participants are allocated by means of a

prearranged balanced randomization list with code
numbers to receive a 1.0 ml (10 mcg or 5 mcg)
intramuscular injection of vaccine at o. 1 and 6
months. Fifty-five receive 10 mcg doses and 55
receive 5 mcg doses.
As per an addendu111 to this study. 55 recruits receive
a 0.5 ml (2.5 mcg) injection of vaccine at o. l and 6
months.
Vaccinees are asked to record their temperature daily
for 5 days after each injection and also to record any
local or systemic complaints they may have during this
period.
A blood specimen (10 - 15 ml) is obtained from each
part I cipant approximately two weeks before the first
obtained at 1. 3, 6, 7, 12 and 24 1n0nths. The samples
are assayed for HBsAg, anti-HBc. anti-HBs and ALT.
These assays are completed by Dr. Papaevangelou.
RESULTS: HEALTHY TEENAGERS:

10 mcg Lot 979/C-K564 at 0, land 6 months
5 mcg Lot 985/C-K732 at o. 1 and 6 months
2.5 mcg Lot 985/C-K732 at 0, 1 and 6 months
InJection Number
Dose Level ...L ..L ..L
10 mcg 55 55 55
5 mcg 55 55 55
2. 5 mcg 55 55 54
Three individuals, one from each group, were

seropositive at the time of immunization and are
excluded from the serologic analysis.
24771/2
1/15/86
00b2b
Study 819
RESULTS: (CONT'D) 2. Serologic Results:
At 7 months serologic data are available for 52,

54, and 53 study participants who received 10, 5,
and 2. 5 mcg doses, respect he ly. The
seroconversion rates at 7 nronths were lOOl for all
dose levels when the cutoff was S/N >2.1. When
the cutoff was mIU/ml ~10. The rates- were 100%
for 5 and 10 mcg and 94% for 2.5 mcg. ~t 1 and 12
months the fo 11 owing ant f-HBs responses were
noted. Table 1 shows seroconversion rates and
GMT's through 12 110nths of follow-up.
- · - - - CIIT (IIIU/1111) - · --- · --

Thne Dose •- \ with Anti-HBs - All -- -- Responders -- -
(ltlnths) Level S/11 ~ 2.1 IIIIU/1111 ::_ 10 V1cclnees SIN~ 2.1 mIU/ial::. 10
7 10 IIIC:9 100(52152) 100(52/52) 3056.9 3056.9 3056.9

12 10 mc:g 100(54/S4) 100(54/54) 583.1 583.1 583.1
1 5 IIC9 100(54/54) 100(54/54) 2553.3 2553.3 2553.3

12 5 IIIC9 100(54/S4) 100(54/54) 498.1 a.1 498.1
1 2.5 mcg 100(53153) M(50/S3) 846.3 846.3 1131.8

12 2.5 mcg 92(49/53) 91(.a/53) 324.7 8.8 S.7.1
3. Clinical Ce!!l!laints
and 54 participants following each injection of
10, 5 and 2.5 mcg doses, respectively. Data
following the third injection has not yet been
entered into the data base. Specific c~laints
and maxi11um temperatures reported during the five
days following the First two injections are
provided in Tables 2 through 7.
Type of Dose Frequency in \ by Injection No.

CCM>laint bevel 1 _2_ _ 3_
Inject.ion 10 IIC9 9(5/55) 6(3/55) 0(0/55)

Site S IIIC9 6[3/55) 9(5/55) 6(3/55)
2.5 IIC:9 13(7/55) 2(1/55) 2(1/54)
Syst1111ic 10 IIICII 6(3/55) 0(0155) 0(0155)

5 IIICII 4(2/S5) 4(2/55) 0(0/5S)
2.5 mcg 6(3/55) 0(0/55) 0(0/~)
24771/3
1/15/8&
00627
Study 819
RESULTS (CONT'D): The vaccine was well tolerated. All complaints

were mild and transient. There were no serious or
alaming adverse reactions attr ibutable to vaccine.
(b)~
One recipient (Case of 5 mcg doses became
borderline positive tor HBsAg at 3 months
(S/N=2.11). His ALT level at this tirae was within
normal limits and he was negative for anti-HBc.
His pre-bleed and 1, 6 and 7 and 12 month
bleedings were negative for HBsAg and anti-HBc.
There is no evidence to suggest that this
individual has become infected. It appears likely
that the low positive test for HBsAg was spurious.
PUBLICATIONS: Dandolos E, Roumeltotou-Karayannts A, Richardson SC,

Papaevaneglou G. Safety and inmunogentctty of a
recombinant hepatitis B vaccine. Accepted for
publication in J Med Virology 1985.
Papaevangelou G, Oandolos E, Rounieltotou-Karayannis A,
Richardson SC. Inmunogentcity of recombinant
hepatitis B vaccine. Lancet 1985; 1:455-6.
24771/4
1 /15/86
Study #819
Antibody Responses lfflong Initially Seronegative Healthy Teenagers Following Vaccination with 10, 5, or 2.5 rncg Oases of
Yeast Recarblnant Hepatitis Vaccine B Lot 979/C-K564 or Lot 985/C-K732 at 0, 1 and 6 l'lonths In Study 819
10 mc:g ~lot C-K564l 5 mcg {lot t-K1322 2.5 mcg tLot C-K732l
\ wl th Anti-!iBs _ . _ GfiT {mIU/ml l 1. with Anti-HBs GHT {mIU/mll \ with Anti-HBs GHT {mIU/ml)
ResQ!!!:!ders ResE!Qnders Reseonders
Time SIN:!:. mlU/ml All S/N :!:. mIU/ml SIN:!:. mIU/ml All S/N :!:. 111IU/rnl S/N ~ mIU/ml All S/N :!:. mIU/ml
110s. 2. l :!:,10 Vacclnees 2.1 :!:. 10 2. l ~10 vaccinees 2.1 10 2.1 :!:. 10 Vaccinees 2. 1 :!:. 10
61(36/54) 39(21/54) 10. 7 32.8 116.6 59(32/54) 19(10/S4) 4.0 10.s 58.5 59(32/54) 26(14~54) 4.3 9.90 24.5
3 100(53/53) 95(51/!>3) 213.3 213.3 245.8 100(54/54) 94(51/54) 107.9 107.9 127,4 91(49/54) 67(36/54) 23.7 31.8 63.3
6 100(53/53) 98(52/53) 199.0 199,0 211.0 100(54/54) 100(54/54) 107.5 107.5 107 .5 94(48/51) 71(36/51) 24.7 31.3 59.4
1 100(52/52) 100(52/52) 3056.9 3056.9 3056.9 100(54/54) 100(54/54) 2553.3 2553.3 2553.3 100(53/53) 94(50/53) .846.3 846.3 1131.8
12 100(54/54) 100(54/54) 583.1 583.1 583.1 100(54/54) 100(54/54) 498. 1 498.1 498.1 92(49/53) 91 (48/53) 324.7 498.8 547. 1 •
24771/5
12/31/85
0
0
O-
N
QD
Table 2
RECOMBINANT HEPATITIS B VACCINf:
STUDY 0819
TREATMENT
LOT ~ER Cl<564
DOSE 10 MCG
PATIENT CLASS HEALTHY TEENAGERS
• TOTAL VACCINE ES I S5 PATIENTS I - DOSE 1 I

•----------------------------------------------------------------------------1
• DAYS POST VACCINATION I NIJt18ER
CLINICAL
COMPUIHTS
•----------------------------------------------------------------------------1
• 0 • l • 2 • J • 4 • S I
MITH
ICONPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION. LOCAL IIHJECT. SITU I o • 0 • 5 I 0 I e I o I I s
• ( O.0Y.I • I 0.0Y.) • I 9.1%) • I 0.0)0 • I 0.0%) I t o.o;o I I t 9.17.)
-----------------------------------•----------l----------•----------•----------•----------1----------1----------1-----------
sOREHESS I o I o I s I o I I I o I I 5
• I o.o:o • ( 0.0iO • C 9.1%) • I 0.0?.) J I 0.0)0 I t 0.0%) I • I 9.UO
-----------------------------------•----------•----------•----------•----------1----------1----------1----------•-----------
SYSTEMIC • 0 I l • 2 • 0 • 0 I O I • 3
I I 0.0)() I I 1.87.) • I 1.6%) • t 0.0?.I • ( 0.0%) • I a.ox, I • ( 5.57.)
---·--------------------------------------------
1 I I •
WHOLE BODY/GENERAL I o I l I 2 I O • 0 I a I I 3
O.0Y.I I c l.87.1 • I J.6%1 I I o.0?.I • I 0.0iO I I 0.0?.I I I I 5,5?.I
I • I • I
MALAISE I o I o • 2 I I I o I o I I r
o.a:o • c o.or.1 I • J.6?.I I c 0.07.1 I c o.ox1 I c o.or.1 I • c J . 67.l
I I I I I I I
HEADACHE I O I 1 • 1 • O I O I O I I 2
I c o.o::o • , 1.e:o I c 1.e:o • , r
o.or.1 • c o.ox, I ,
3.6ln o.o;o I ,
-----------------------------------1----------l----------l----------1----------l----------l----------l----------•-----------
PERSOHS MITH Cot1PLAINTS I O I 1 • 6 I o • 0 I O • • 7
I , 0.07.1 I , 1.ez, I , 10.97.) • , o.ox1 I c o.oz1 I t o.oz, I • c 12.1-:1
-----------------------------------1----------•----------•----------•----------•----------I----------I----------I-----------
PERSONS MITH HO COMPLAIHTS I O I Sit • 49 I 55 I O I O • • 48
I r 0.07.1 I I 911.2:f.l I 1 89.1:f.J I 1100.or.1 • 1 o.ox1 I I o.oz, I I r 87.3?.I
-----------------------------------1----------l----------•----------•----------l----------l----------l----------•-----------
PERSONS WITH HO DATA I O I O I O I O I O I O • I 0
I r 0. O?. I I ( 0. 07.) I I I • 07.1 I t 0 • 0?. I I C O. ox I I l 0. 07. I I I I 0 • 07. I
Q
0
O-
rv
~- -0
Table 2 (cont. )
l!ECOl18INANT HEPATI TIS B VACCINE
Sf\JDY 0819
TRElTt1EHT
LOT NJM8ER CK564
005£ 10 MCG
I TOTAL VACCINEES C 55 PATIENTS) - DOSE Z •

1----------------------------------------------------------------------------•
I OAYS POST VACCitt.l.TIOH • HU118ER
CLINICAL
COt1PlllNTS
•----------------------------------------------------------------------------1
• 0 I 1 I Z • 3 I 4 • 5 •
WITif
.COMPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••••••••••••• ••••••••••• I•••••••••••••••••••••
REACTION, LOCAL IINJECT. SITEI •I 2 •I 3 •• 0 •• o •I O •• 0 I• •I 3
I , 3.67.1 I ., 5.57.1 • 1 o.ox1 • , o.o;n I , o.or.1 • , o . o,., I • , s.sr.,
-----------------------------------•----------•----------•----------•----------•----------•----------1----------•-----------
SORENESS • 2 • J • 0 • O I O I O I • 3
I ( 3.67.1 I ( 5.5:t.l I ( o.o:o I ( o.o;o I ( o . o:o I ( o.o;o • I I s.s:o
-----------------------------------1----------l----------t----------l----------•----------•----------
PERSONS WITH COt1PllINT!l I 2 I 3 I O I O • 0 • 0
l----------•-----------
I f J
I 1 3.67.l I t s.57.1 I I o.o:o I I o.or.1 • t 0 . 0;.:1 I t o . OY.I • I 1 5.!IXl
-----------------------------------•----------1----------•----------•----------•----------
PERSOHS WITH HO COtlPLAINTS • 53 I 5Z • 55 • 0 • 0
•----------•----------•-----------
• 0 • • 52
• , <H>.47.l I c ,~.57.1 I noo.o;o • c o.o;o • , o.ox1 • , o.o;o • I 1 ,~.57.1
-----------------------------------•----------1----------1----------1----------l----------l----------•----------I-----------
PERsOHs WITH NO DATA • 0 I O • 0 • 0 I O • 0 I • 0
• C 0.07.1 I C 0 . 07.1 • ( 0.07.) I ( o.o;o • ( 0.07.) • l 0.07.1 I I I o.o;o
Q
0
a-
u,,
0
--
Table 3
PATIENT COUHT MAXI~ TEMPERATURES
RECOM8INANT HEPATITIS B VACCitlE
STUDY 0819
TREAfflEHT
LOT HUttBER CKS64
DOSE 10 t1CG
PATIENT CLASS HEALTHY TEENA6£RS
----------------------------------------------------------------------------------------------------------------
f TOTAL VACCIH£ES t 55 PATIENTS! - DOSE l I ----- -
It--------------------- ·-----------------------------------------------------------------1
DAYS POST VACCINATION I .u18ER
11.lX TEHPERATURE
CDEG F, ORAL I
l---------------------------------------------------------------------------------------1
I a I l I 2 I 3 I ft I s • I I NA><MITH
TEHP
••••••••••••••••••••1111••••••••••-•l•••••••••••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••I••••••••••
< 9'J
•
I O
I Sit I• 50 ••
I 55
II O
I
I D
•• II 49
I c a.o,o I c 9e.z;o I c 90.97.1 I 1100.0;0 I 1 0.0:1.1 I I o.o::o I I t a9.1;0
I I I I I I • I
99 - 99. 9 I o I 1 I 5 I a I o I a I I 6
I < o.07.1 I c 1 .87.I • 1 ,.uo • c o.o,n I I a.oY.1 I I o.aio 1· • 1 10.9lO
------------------------l----------l----------l----------l----------1----------1----------I---------------------I-----------
TE11PERATURE TAKEN I 0 I 55 I 55 I 55 I D I D • I 55
I ( O.OiO I naa.D7.J I UOO.D7.J I uoa.a;o I I 0.07.1 I ( 0.07.) I I noo.a;o
------------------------l---------l----------l----------l----------1----------I----------I---------------------I-----------
TEl1PERlTIJRE HOT TAKEN I 55 I O I O • o I 55 I 55 I I o
I UOD.07.1 I l 0.07.1 I l 0.07.1 I ( o.a;o I (100.0i!I I noo.o;.1 • I ( 0.01.I
0
0
~
'9
-
u,I
Table 3 (con_t. )
PATIENT COUNT NAXIN\i1 TEMPERATURES
RECOl181HANT HEPATITIS 8 VACCINE
STOOY 0919
TRUTt1£HT
LOT HUM8[R CK564
DOSE 10 t1CG
PAlIEHT CUSS HEALTHT TEENAGERS

1----------------------------------------------------------------------------------·----
I
I NU118ER
l--------------------------------------------------------------------------------------1
HAX TEMPER ATURE
I DEG f, ORAL I
........................,
I
I
II I
, l I
,
2 I 3
, I 4
, I 5 I
, I
, , , MITH
I HAX TEt1P
.......... .......... .......... .......... .......... .......... .......... .......... .•......••
I I I I I I I
< n I 55 I 53 I 55 I o I o I o I I n
I noo.o:-o I , 96.41.t I uoo.o7.t I I a.07.1 I 1 0.07.t I , 1 .or.1 I I 1 96 .47.t
I I I I I I I I
99 - 99. 9 I o I 2 I o I o I a I o I I 2
I 1 0.01.1 I 1 3.67. t I I o.07. 1 I I a.07.1 I I a. o7.t I I o.D7.I I I I J .67.t
------------------------l----------
TEttPERATURE TAKEN I 55
l----------1----------1----------1----------I----------I---------------------
I 55 I 55 I a I O I O I
I-----------
I 55
I noo.or., I noa . or., I 1100.a:o I I o.a:o I 1 0.07.1 I t ,.ox, I I 1100 . 0:0
------------------------l----------l----------l----------l----------l----------
TENPERATURE NOT TAKEN I O I o I a I 55 I 55
l----------1
I 55 I
---------------------1I -----------
o
I ( 0 . 0l!I I ( 0.0l!) I ( 0.0l!I I llDCl.07.) I 1100.07.) I (lOD.0)O I I I o.o;;o
0
0
0-
"'""
·"
Table 4
RECOMeINANT HEPATITIS 8 VACCINE
STUDT 0819
TREATMENT
LOT NUM8ER CK732
DOSE 5 MCG
PATIENT CUSS HE ALTHY TEENAGERS
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I 55 PATIENTS I - DOSE l I
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NU11BER
CLINIC AL
COttPLAINTS
1-----------------------------------------------~----------------------------I
I O • l . 2 I 3 • 4 . 5 .
WITH
•cOHPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••• ••••••••••• l•••••••••• l••••••••••l•••••••••• ••••••••••• I••••••••••
REACTION. LOCAL UNJECT . SITEI
I• O
•• 0
I• 3 II O I• O
•I o •• •• 3
• I O.OlO I I O.OXI • C 5.SXI I I 0.0XI • I O. OXI • I O. Ol!I • • I 5.SY.l
-----------------------------------1
SORENEss I ----------•----------•----------
O • 0 • 3 I•----------•----------1----------•----------
O • 0 • 0 •
I-----------
I 3
I I 0.01.1 I I O.OXI • I 5.SXI I I 0.01.1 • I O.OX) • I O.OXI • • I 5.SY.)
----------------------------------- •----------l----------•----------1
srsnMic • 0 I O • 2 I
----------•----------•----------•----------
O • 0 • 0 I
•-----------
I 2
I I o.o;o I I O. OXI I I 3.6XI I I O.OiO • I o.o:o • I O. OX) • • I 3.6)0
------------------------------------------------------------------------------------
1 • I I • I •
WHOLE BODY /GENER AL • 0 I O • 2 • O I o I 0 I • 2
o.o;o I t o.o;o I t 3.6Z> I 1 0.0:1.1 I I o.ox1 • c o . o:o I I 1 3.,x1
MALAISE • o •• 0
•
• 2 I
I
D I
I
o
•
I o
I
I
•
• 2
0.01.1 • I 0.01.) • I 3.6Y.J I I O.OX) • I O.OXJ I C O. OXI • I I 3.6¼1
I I I I I I I
HEADACHE I O • 0 • l I D I O • D I I 1
I I 0 . 01.1 I t O.OXI I I l.8Y. I I I 0.01.1 I I 0.07.1 I I O.OY.I I • I 1 ,8)(1
-----------------------------------1I ----------l----------l----------1----------l----------l----------•----------1
PERSOHS WITH COHPU IHTS O • 0 I 5 I O I O • O I I
-----------
5
• I 0.0?.I • C o.o;o • I 9 ,1)( ) • I 0.01.1 I I 0.07.J • I o.o;o I • I 9.lY.I
-----------------------------------1----------•----------•----------•----------•----------•----------•----------•-----------
PERSOHS WI TH HO COMPLAINTS • 0 • 55 • 50 I 55 I O • O I • 50
• I o.o:o I 1100.07.1 • I 'J0 . 97.1 f 1100.01.1 • I 0 . 0%) • I 0.0)(1 I I I 90,9¼)
----------------· ------------------1----------1----------•----------
PERSONS WITH HO OATA I O I O • 0 I•----------l----------•----------1
O I O I D I ----------•-----------
I D
• I o.o:o I I o.ozJ I I o.ox, I r o.ox1 • 1 o.o:o I , o . o:o I I I o.o;o
0
0
0-
""""
-
Table 4 (cont. )
PATIENT CotMT CLINlCll Cot1Pll 1HTS
RECO!IBINANT HEPATITIS B VACCINE
STUOl 01119
TRUTHENT
LOT HUt!BU CK732
DOSE S tfCG
PATIENT CUSS HEALTHY TEENAGERS
I TOTAL VACCIUEES ( 55 PATlENTS I - DOSE 2 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NIJl'8ER
ClIHICAt
C011PlAINTS
l----------------------------------------------------------------------------1
I IJ I l I 2 I 3 I 4 I 5 I
WITH
lt011PLAIHTS .
•••••••••••••••••••••••••••••••••••l•••••••••• l••••••••••l••••••••••l••••••••••l••••••••••l•••••••- •I•••••••••••••••••••••
I I I I I I I I
RUCTION, LOC AL IINJECT. SITE> I 5 I 5 I o I o I o I o I I 5
I 1 9.lY.I I , 9.lY.t I c o.o;o I c 0.07.1 I , o.oio I c o.o:o I I c ,.uo
-----------------------------------l----------l----------l----------l----------1----------l----------l----------l-----------
sOREN£ss I 5 I 5 I O I O I O I O I I 5
I 1 9.1;.1 I 1 9.1x, I c o.ox1 I c 0.01.1 I c o.ox1 I c o.ox1 I I c ,.1;.1
-----------------------------------l----------l----------l----------l----------t----------t----------l----------l-----------
srsn111c I 2 I 2 I o I o I o I o I I ' 2
I I 3.6)0 I ( 3.6:o I C o.o;o I C 0.0)!1 I ( 0.07.I I C 0.0¼1 I I ( 3.67.1
------------------------------------------------------------------------------------
1 I I I I I I
wttOLE BODY/GENERAL I 2 I 2 I o I o I o I o I I 2
3.67.l I I 3.6XJ I c 0.01.1 I c 0.01.1 I c o.ox1 I c 0.07.1 I I c 3.67.1
I I I I I I I
HAlAISE I z I 2 I o I o I o I o I I 2
3.6X) I I 3.6Y.I I C 0.07.) I C 0.07.1 I ( 0.OX) I ( 0.D7.1 I I I ].6Y.I
I I I I I I •
HEADACHE I o I 1 I o I o I a I ·o I I 1
I ( a.ox, I C 1.87.) I C 0 . 07.) I C 0.07.1 I I 0.07.I I ( D.07.1 I I I 1.87.I
-----------------------------------1----------I---
PERSONS WITH t0t1PUUITS I 5 I
.------l----a·----1----------1----------1
5 I D I O I O I
·---------1----------1-----------
D I I 5
I c 9.1:1.1 I c 9.17.1 I c a.ox , I c 0.0;.1 I c 0.0:1.1 I I o.o;o I I 1 9.11.1
-----------------------------------1----------I----------I----------I----------I
PERSOIIS WITH NO CONPLAIHTS I 50 I 50 I 55 I O I----------I----------I----------I-----------
0 I D I I 50
I I 90.97.1 I ( 9D.9:1.) I noo.ox, I ( 0.07.1 I ( a.ox, I ( 0.0:1.1 I I C 90 . 97.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH NO DATA I o I o I o I a I o I a I I o
I c o.07.l I c a.ox, I c a . ox, I I a.ox, I c 0.0;.1 I c o.ox1 I I r 0.0;.1
0
0
....a-
b
Table 5
PATIENT COUNT HAXIMUM TEMPERATU!ES
RECOl'181NAHT HEPATITIS 8 VACCINE
STUDT 0819
TREATMEHT
LOT NUl18ER I CK73Z
DOSE 5 MCG
PAlUHT CUSS: HEAllHT TEENAGERS
I TOTAL VACCINEES I 55 PATIEHTSI - DOSE l I

I•---------------------------------------------------------------------------------------1
DAlS POST VACCIHAllOH I NUl18ER
l---------------------------------------------------------------------------------------1
"AX TEt1P[RAl\JRE
IOU F, ORAll
I
• 0 I
, I
1 I Z
I
• 3 •
•
It • 5
,
•
I
•
, WITH
I ttAX TEHP
................................... ..........•..........•.......... ...•...... ..........•..........•..........•..........
• I I
< 99 I o • S<t I Sl I 55 I o • o I I so
I I O. 07. t I C 98. ZY. J I C 92 • 77. t • 1100. OY. I I I O. OY. I • I O. OY. l I • I 90. 97.1
I I I I I I • I
99 - 99.9 I o I 1 I I
3 o I o • o I I 4
I I O.OiO I C 1.8l0 • C s.s;o I I O.OY.l I I O.OY.I • I O.OiO • I I 7.3%)
I • I I I I • i
100 - 100. 9 • o I o I 1 I o I o I o I I 1
I I o.ox, • c 0.01.1 I r 1.a;o I 1 0.01.1 I I o.or., I t o.o;o I I • 1.8:11
------------------------l----------•----------1----------1----------1----------l----------•---------------------I-----------
TEHPERATURE TAKEN I O I 55 I 55 I 55 I O • 0 I • 55
I ( O.OY.I • UOO.O?.I I (100.0Y.I I 1100.0Y.I I ( 0.07.1 • I 0.0)0 • I 1100 . 0)()
------------------------l----------•----------l----------l----------•----------•----------1---------------------0
TEtlPERATURE NOT TAKEN I 55 I O I O • 0 I 55 • 55 I I
-----------
O
I 1100.0;0 J I 0.07.J • C 0.0%) I I o.OY.l I 1100.07.1 I 1100.07.1 I I I o.o;o
0
0
17'
""
~
-
Table 5 (cont.)
PATIENT COUHT HAXIl1Ut1 TEHPERATURES
RECottBINAHT HEPATITIS 8 VACCitlE
STUOY 0819
lREI.Tt1Etn
LOT tUIBER I CK7'J2
DOSE 5 11CG
PATUNT CLASS: HEALTHY t£EHA6ERS
• TOTAL VACCIHEES I 55 PATIENTSI - DOSE 2 I

•---------------------------------------------------------------------------------------
• OAYS POST VACCINATION
1• HU11BER
MAX TEMPERATURE 1--------------------------------------------------------------------------------------- •I HAWITH
IOE& f, Ol! ALI • 0 • l
I
• 2 •
•
3 •
,
ft
•
• 5 •
•
•
I
XTEl1P
························•··········•··········•.......... ..........•.......... •.......... •..........•..........•..........
I I I
< ,, I 53 I 51 • 55 • o • o I o I I s1
• I 96.lfY.I I ( 96.ltir.l • U00.0Y.I • I 0.07.1 I I 0.0Y.I • I o.o;r. 1 • I ( 96.ltiO
99 - 99. 9 I• z I• z II o •• o II o •• o I• II 2
• ( 3.6X I • ( 3.6)0 I I a.ox, • I O.OXI I I O.OXI • I 0.0)0 • I t 3.6%1
------------------------l----------
TEHPERATURE TAKEH • 55
t----------l----------l----------l----------l----------1---------------------1
• 55 I 55 I O • 0 I O I • -----------
55
I U00.07.1 I (100 . 0)0 I uoo.ox, I I 0.07.1 I I 0.07.) I I o.o;o I I uoo.o::o
------------------------l----------•----------•----------l----------•----------1----------1---------------------
TEMPERATURE HOT TAl<EH I O I O • 0 • 55 I 55 I 55 I •-----------
I 0
. • I 0.07. ) • I 0.0?.I • t o . o;o • 1100.07.1 • 1100.0iO • U00.11?.I I • I o.o:o
0
0
a-
""'a-
-
Table 6
PATIENT COUNT CLIHlCAL COMPLAINTS
RlCDt1BIHANT HEPATITIS 8 VACCINE
STUDT 0819
TRUTl1ENT
LOT NUM8ER CK7:U
DOSE t.5 ttCG
PATIENT CUSS HEALTHY TEENAGERS
--------------·-------------------------------------------------------------------------------------------------------------
• TOTAL VACCINEES f 55 PATIENTSI - DOSE 1 I
l----------------------------------------------------------------------------1
I OATS POST VACCINATION I HUt19ER
CLINICAL 1----------------------------------------------------------------------------I WITH
COMPLAINTS • 0 I l I 2 I 3 I 4 I 5 I IC0t1PLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
• I I • I I I I
REACllOH, LOCAL flHJECT. SITE I I 7 I 7 I t I o I O I o I I 7
I f It. 77.1 I f 12. 7i0 I f l.6i0 I f o.o;o I t o.o;o I 4 o.o:o I I f 12. 7XI
-----------------------------------1----------l----------l----------l----------1----------l----------l----------l-----------
soRENESS I 7 I 7 I 2 I O I O I O I I 7
I f 12.7Y.I I f 12.7Y.I I f l.61.1 I I 0.01.1 I c 0.01.1 I I 0.01.1 I I c 12.71.1
-----------------------------------1----------l----------•----------1---------
SYSTEMIC I J I J I o I fl
·1----------I----------I----------I-----------
I o I 0 I I 3
I f 5.51.1 I f 5.51.1 I f 0.01.1 I I 0.01.1 I I o.07.J I f o.o:o I I I 5.57.1
----------------
MHOLE l!IOIJT/GEHERAL I J I l 'I O II 0 I o I 0 I I 3
S.5)0 If s.s;o I f O.OiO I I 0.01.1 If o.o:o If 0.01., I Il 5.5)()
I I I I I I I
MALAISE I J I l I a I o I 0 I o I I 3
I f S.SiO I f 5.57.1 I f O.OiO I I O.fl)(I I f O.O)(J I f 0.0)(1 I I f 5.S7.1
-----------------------------------l----------1----------1----------1----------1----------l----------l-----
PERSOHS MITH COMPLAINTS I 7 I 7 I 2 I o I o I o I
·----I-----------
I 7
If 12.7Y.I If 12.7l!I If 3.61.1 I I o.oY.I If o.o:o If 1.01., I If 12.n1
-----------------------------------1----------l----------l----------l----------l----------•----------I----------I-----------
PERSOHS MITH NO COMPLAINTS I 48 I 48 I 51 I o I o I o I I 48
I f 87.31.J I f 87.31.1 I f 96.41.1 I I 0.0)0 I I 0.01.J I f O.OiO I I f 87.37.1
-----------------------------------1----------l----------l----------1----------I----------I----------I----------I-----------
PERSONS WITH HO DATA I o I o I a I o I o I o I I o
I f o. o;o I I o. OY. I I f O. 01.1 I I o. OY. I I I o. 01.1 I f o. 07., I I f o. 07. i
0
0
a-
~
--..!
.....
Table 6 (cont. )
PATIENT COUNT ClJHJCAl COMPLAINTS
RECOMBIH.-HT HEPATITIS B VACCJIIE
sruor oe19
TREATttt:HT
lOT HU111'lER CK73t
DOSE 2.5 t1CG
PATIENT CLASS HEALTHT TEENAGERS
• TOTAL VACCIHEES C 55 PATIENTS) - DOSE 2 I

l----------------------------------------------------------------------------1
I OATS POST VACCitlATIDH I 1-U1BER
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------1
• 0 • l • 2 I 3 I <t I 5 I
WITH
ltot1PlAIHTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••-••••••••••••••••••••••••••••••••••l••••••••••l••••••••••I••••••••••
REACTION, LOCAL UNJECT. SITEI
•I l
I
I O
I
I O
I
I O
I
• 0
I
I O
•
I
II l
I 1 1.e;o I 1 0.01.1 I 1 0.0:t.1 I c o.oz1 I, o.a;o I, o,o,., I Ic 1.8XI
-----------------------------------1----------l----------l----------l----------t----------1----------l----------1-----------
sOREHESS I 1 • o I o I o I o I o I I 1
I I l.8i0 I I O.OiO I ( 0.0)(1 I I O.CJZI I I 0.07.) I I 0.07.1 I I C 1.87.)
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS Wiffl CottPLAIHTS I l I O I II I D I D I O I I l
I I l,87.) I ( 0.07.) I I 0.07.) I ( 0.07.) I I 0.07.1 I I O,CJZI I I I 1.ex,
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsOHS WITH HO cOMPUIHrs I 54 I 55 I · 55 I o I o I o I· I S<t
I I 98.27.J • 1100.07.J I uao.o:;o I C D.07.) I I 0.07.I I ( o.o;o I I C 98.27.I
-----------------------------------1----------I----------I---------I----------I----------I----------I----------I-----------
PERSONs WITH HO DATA • 0 I D I O I O I O I O I I O
I I O. 07.1 I I O. O?.) • ( 0. 07.1 I I D. ax I I I O. 07. I I C O. oz I I I ( D. oz l
0
0
0-
1.,d
--
(Ill
Table 7
PATIENT COUNT "AXI11UN TEMPERATURES
AECot'8IHAMT HEPATITIS 8 VACCINE
STUDY 0819
lREATt1EtfT
LOT HUN8ER CK732
DOSE 2.5 MCG
• TOTAL VACCIHEES ( 55 PATIENTSI - OOSE 1 I

I•---------------------------------------------------------------------------------------•
DAYS POST VACCIHATION I HU118ER
MAX TEMPERATURE •------------------------------------------------------------------------------------- --• WITH
( DEG F, ORALI • 0 • 1 • t • 3 I It I 5 I • I HAX TEt1P
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••I••••••••••••••••••••••••••••••••
< 99 I• ss •I 53 I • 55 • • o •I o •I o •I •• 53
I (100.0Y.I I ( 96.47.) • (100.0)0 • I 0.07.1 • I 0.0)0 • I 0.0)0 • I I 96.ltiO
99 - 99. 9 •
I o •• 2 •• o •• o •I o I• o •I •I 2
I ( 0.07.1 I ( 3.t.7.) I t O.OY.I I I 0.0:,:1 I C o.o:o • C o.o:o • I I 3.6Y.l
------------------------•----------1----------•----------
uHPEAATlll1E TAKEN I SS • 55 • 55 Il----------•----------l----------l---------------------l-----------
O • 0 I O • • !l!I
• noo.o:o • ,100.ox, I 1100.0:0 I I o.o:o I I o.ox, • 1 o.ox, • I 1100.ox,
------------------------•----------•----------•----------1----------1----------•----------•---------------------•-----------
TEHPERATURE NOT TAKEN I 0 • II • 0 I 55 I 55 • 55 • • II
• C O.IIY.) • t O.O:o • C O.o;o • 1'100.0lO I UOO.OlO • 1100.0Y.I I • I O.OXI
0
0
O'
""-D
-
Table 7 (cont.)
PATIENT CO\MT "AXI,-,n TEHPERATURES
AECOl'18IHAHT HEPATITIS B VACCitlE
STUDf 0819
TREUHEHT
LOT HU113ER CK732
DOSE 2 , 5 ttCG
PATJEMT CLASS: HEALTHT TEEHASEAS

•-----------------
• .-------------------------------- ·------------------------------------1I Nlll1BER
HAX TEMPERATURE
IDEG F, ORALI
•--------------------------------------------------------------------------------------1
I O I 1 • 2 I J • 4 I 5 I I
WITH
I NAX TEHP
••••••••••••••••••••••••••..•••••.. l•••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••"••l•••••••••• I••••••••••
• • • I I I I I
< 99 • 55 • 55 • 55 • o • o I o I I 55
I (100.0ll • llOO.OX). 1100.0X). ( O.DXl. I O.OXI I I O.OXI I I 1100.0XI
------------------------l----------•----------l----------•----------•----------1----------1---------------------t-----------
TEnPEAATURE TAt<EH • 55 I 55 I 55 • 0 • o I o I I 55
I 1100 . 0XJ . 1100.0Xl . 1100.0XJ I I O.OXI. ( O.OXl I I D.OXI I I 1100.0X)
------------------------1----------1
TENPEAATURE NOT TAKE N I D •
----------•----------•----------•----------l----------t---------------------l-~---------
0 I 0 • 55 • 55 I 55 I • o
I t o.oz, I t 11.0:0 I t o.o;o • uoo.ox1 • uoo.o;o I 1100.0:0 I I « o.ox 1
:::,
0
O'
~
0
-
00b4t
Journal or Medical VirolO&Y 17:!7'.-'2 (1915)
Safety and lmmunogenlcity of a

Recombinant Hepatitis B Vaccine
E. D1ndolo11, A. Roumellotou-K.arayennhl, S.C. Richardson, and
G. Papaevangelou
National Centre for Viral Hepatitis, Athens School of Hygiene, Athens, Grwce
evaluared uing s.,.,

A hepatitis 8 vaccine produced in yeast by recombinant DNA technology was
and 10-,.g doses in a rudomized lria1 lastinJ 7 monllis in
110 male armed force, recruits aged 17-19 years. Results were compared fO dl0Se
· • of an idelllic:al trial of a plasma«rived vaccine, No aller,;c reactions 111ere
observal, and die me of mild side effec:tS was similar to lhe pluma-deriYed
nccine. Seroconversion raies in lhe fim monlh were 60~ (33/SS) and 671' (371
5.5) with the s-,.g and 10-lolg doses of the recombinant vaccine, respectively. All
panicipants scroc:onvened by 3 months, and none loa antibody. These results are
very iimilar to dl05C for plasma«rived vaccine. Comparison of tiua of antibody
to hepatitis B surface anti,en (anti•HBs) showed a slightly hiper level with lhe
IO-,., lhan with the .5.,.,
dose of lhe recombinant vaccine . Geometric mean titTeS
of anti-HBs after ·lhe booster dole were similar in the 5-,ig and 10-,ag dose
recombinant vaccine lfOUps (2,620 and 2.748 IU/l, respectively) and in the 5•µ1
plasma-derived vaccine sroup (3,591 IUfl) but sipuficantly higher (9,227 nJ/1)
with the I0-111 dose of lhe pluma~erived vaccine:. These raults confirm the
safery and immunoaenicity of the recombinant vaccine, alchouJh funher SCUdy is
needed on the duration of immunity.
Key wonts: active lmln-prophyluis, bepatills B, plas,u-deriftd hepatitis B wacdm, rKOIIIM-

aaat bepatitis I vacdae
INTRODUCTION
The safety and i1M1unogcnicity of plasma-derived hepatitis B vaccines have
been amply dcmonstnucd by clinical trials in various high-risk groups in different
pans of the world [Szmuneu Cl al, 1980; Maupas ct al, 1981; Beasley et al, 1983).
However, the high cost and limited availability have prevented widespread use of
these vaccines, especially in the less developed areas where lhey arc needed most.
Vaccination programmes are at prcsem &cncrally limited to groups a1 high rislc or
infection, such as hospital personnel. Within mese programmes, acceptance may have
been affected by unfounded loss of confidence in the ufety of the vaccine, following
AccCpled for publication April I, 1915.
Addnss n!pnnt nq&MSU to Pref. G . Papoevangclou. Nalionlll Cenw for Viral Hepetitis, Adlefts School
of Hraicne. P.O. Bot. 14015. Alhena 115 21. Greece.
© 1915 Alan R. Ura, lite.

OOb42
Recombinant Hepatitis B Vacrine - 59
isons at each time point. All analyses were carried out after logarilhmic tramforma-
tion of anti-HBs titres.
RESULTS
The trial was completed in all but two rec:ruiis, both the losses being from the
group receiving the 10-µ.g dose. One was lost from the :nudy after rec:civing the
second dose and the other after the booster dose. No participant developed either
clinical or asymptomatic viral hepatitis, and neither anaphylactoid nor other allergic
reactions were observed. Mild side effects were reported, but no case of fever above
37.S°C was noced, and no local discomfort or pain lasting for more lhaJl 1 day. Toe
overall frequency of side effedS was very similar to that reported for the plasma-
derived vaccine in the earlier study (Table [).
The two groups receiving recombinant vaccine showed a similar and rapid
immu~ response (Table m. Both of the recruits who did not complccc follow-up had
already seroconvcncd in the first month. All participantS had seroconvcned by 3
months, and none lost antibody. These rates arc very similar to those recorded in the
trial of the plasma-derived vaccine. Differences in seroconvenion rates at 1 month
between the four groups in Table II are not significant (xi '""5.26; P • 0.15).
Geometric mean titres (GMn of anti-HBs are shown in Table m.
Multivariate
comparison between the two recombinant vaccine groups shows that they do not
differ in rates of increase of anti-HBs (F3, 104 = 1.99; P > 0.1). The 10-,ag ,roup had
significantly higher GMT of antibody overall than the 5-,.cg group (tio& • 2.08; P <
0.05)_, although lhe difference appears to be small after the booster dose.
Multivariate comparisons of the anti-HBs profiles in the 5-pg and 10-p.g recom-
binant vaccine groups against the corresponding plasma-derived vaccine groups show
TABLE I. f'requeKJ of Side Effect.I by Type of

VKCille (SulnnNd Ovel' AdmlaisU'atiofts o( Va«iae)
.Recombinant Pluma-derived
Side ~ffect vaccine(~) vaccine ( " )
Local paia 6.0 9.0
Fever <37.5•C 16.3 11.1
Ocher 2.3 2.l
Tow 2• .6 22.,
TABLE U. Number (1') Gt Serocollftftftl (uti-HBs > 2.1 ltJ/1) bv Mooch IDd Type or Vacdne
RCCOlrlbinaM VMXUIC Plasllla-derivcd vaccine
10 ... .5 ,.. 10,-.1
'.Ill
Mondi (N • 55) CN • 55) (N • 50) IN• 50)
I 33 (e0) 37 (67) 40 CIO) 32 (64)
3 55 (100) So& (100)" 49 (91) •9 (91)
6 55 (100) 54 (100,. 49 (91) 49 (91)
7 55 (1001 53 uoo,• 49 C91) 50(100)
"One penon lolt IO fo&w-up .
.,._ pcnons lost.
00643
Recombinanl Hepatitis B Vaccine 61
population, with all panicipants in both the trials of recombinant and plasma-derived
vaccines being males of similar age living under exactly similar conditions.
Comparison of the 5-µg and 10-µg doses of recombinant vaccine shows a small
advantage to the I0-1,1g dose oYerall in terms of GMT anti-HBs, although any final
difference is slight. Davidson and Krugman {1985), with older vaccinees of both
sexes, reported a final (8 months) GMT anti-HBs in the 10-pg group more than
double that in the 5-µg group, although the statistical significance is not staled.
Irrespective of dose. all participants in our trial reached the 10 IUfl generally regarded
as protective. Only five (4.6~; two from the 5-µg group and three from the 10-µg
group) had titru lower than 100 IU/1.
Our results confinn reports of the safety and immunogenicity of the Merck;
Sharp and Dohmc recombinant yeast hepatitis B vaccine [Jilg et al, 1984b; Davidson
and Krugman, 1985). The minor differences observed in the immune response stress
the need for more extensive studies in various population groups under consideration
for vaccination, before the appropriate dose and vaccination scheme arc decided.
Similarly, further follow-up is required to establish the duration of protective levels
of antibody [Jilg ct al, 1984a; David.Son and Krugman, 1985). Finally, in assessing
the efficacy of the vaccine, infonnation concerning the quality of the anti-HBs induced
should complement the data on lhe anti-HBs levels achieved [Brown el al, 1984).
ACKNOWLEDGMENTS
This study was supported by a grant from the Ministry of Health and Welfare
of Greece.
REFERENCES
Beasley RP. Lee OC, Roan C, Hwan1 L. Lan C. Huans F. Chen C (1983): Prevention of perinarally
uusmiacd hcpatiliJ B vinls infections widi hq,aliliJ 8 immWIC 11obulin and hepatitis 8 v~ne.
Luc:ec ii:1099-1102.
Brown SE. Zuckerman AJ, Howard CR. Sieward MW (19M): Affinity o( &JHibody rcsponsa in man IO
hcpaiilis B vaccine dacrminc:d widl sylllhetic pcpcidcs. uncci ii: 184-117.
David&on M. Kni&1na11 S (1985): lmmuqCllicily of rccombinanl yeast hepatitH B vaccine. l...anc:el
i:108-109.
Hollinacr FB. Adam E. Hcibcrs D. Melnick JL (1912): lt.apomc II) hlpatitis B vac;cinc i.n a youaa ■d11l1
population. ID Szmunc:as W, Alter HI. Maynard JE (eds): •Vin! Hepatitis . 1911 l111emalional
Symposium.· Philadelpbia: Franklill lns&ilW Press. pp 451-466.
Iii& W, Schmidl M. Deinhardt F, Zac:hoval R (1914a): Hepatitis 8 VKCinatioa: How lone doe$ proccaion
last? l..aftcc( ii:451.
lilg W. Schmick M. 2-lek Ci. Lorbeef B. Wilste B. Deinhardt F {1914b): Clillical enlllllioft of a
rccombinanl llq,elil.is B vKCinc. l.anccl ii:1174-117-'.
Maupu P. Chil'OII IP, Bann F. Couraagci P. Goudeau A, Perrin I. Denis F. Diop Mar I C1981 ): Efficac}
of bepalilil B YKCine ill prevenlion of early HBsA.1 Qrrier swe in children. Controlled trial ill
Ill endemic IICa (Senefaf). uncet i:219-292.
McA.leer WJ, Buynak EB, Maigeaer RZ, Wampler DE, Miller WJ, HilltllllJI MR (198'): Hu111111
hcpaticis 8 v111;c:ine from recombilllllt yCUl. N1111rr 307:171-110 .
Morrison DF (1976): "M11kivaria1e Statistical Methods," (2nd ed). New York: Mc:Cira,..•Hill.
Paplcv111,elou G, llou~liolou•Kanyannis A, Viuoulis C. Richardson SC. Knllfll&n S (1985): lmmu•
no,cruciiy o( a 5 ,.g dole hepeciw B vaccine. Joumal of Medical Viroloay . 15:65--69.
Pnpaevangelou G. Rownelioc.ou•K.vayunil A, Viuolalii C. Swhop,li~ P. Kolaius H. Kniaman S
(1983): Sllfccy and immunoscnicity o( a f'unher reduced doK (10 nq) of lhc hq,elitis B vaccine.
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SUMMARY - HEALTHY CHILDREN
To date, a t otal of 258 healthy infants and children, 3 months to 11 years of

age who were negative for hepatitis B markers, have been vaccinated with
hepatitis B recombinant vaccine. Clinical data for all 3 injections are
available on 100 infants and children. Seven to 8 month serology data are
available on 97 infants and children. Antibody and clinical responses to 5, 2.5
and 1.25 mcg doses of the vaccine administered at o. 1 and 6 months were
evaluated. The vaccine was very irrmunogenic and well tolerated in this
population. Clinical complaints were minimal and transient. In general,
children 3 months to 11 years show an earlier response and develop higher titers
of antibody than do adults. Seroconversion (S/N >2.1) exceeded 94% after 2
doses regardless of dose level. Protective levels of antibody (mIU/ml >10) were
induced in 100% of vaccine recipients, one month after the third injection,
regardless of dose level administered. At 12 months, all children surveyed
still had titers of mIU/ml >10.
Immunogen1c1ty
Anti body to hepatitis 8 surface antigen was measured at 1, 2, 3, 6, 7/8 and 12
months post vaccination. Data from study 809 involving 80 children who received
either 5, 2.5 or 1.25 mcg doses were statistically analyzed. No significant
effect of log dose level on seroconversion rates was found using either a cutoff
of $/N >2.1 or mIU/ml >10 (see Appendix I for statistical methods used}.
Seroconversion for all three dose levels and either cutoff was greater than 82%
at 3 months, 91% at 6 months and 100% at 7/8 months (Table 1).
When each dose level was analyzed for the effect of age on seroconversion rates.
younger children (under 4 years vs 5-12 years) who received the 2.5 mcg dose
showed a significantly higher rate at 1 month for a cutoff of S/N >2.1 (p =
0.028) and at 3 months when the cutoff was mIU/ml >10 (p = 0.022) [Table 2).
However, seroconversion was excellent for both age groups by 6 months.
log titers increased significantly with log dose level at 6 (p = 0.03) and 7/8
months (p <0.01) (Table 3). Geometric mean titers for all vaccinees at 7 months
were 15965.5 mIU/ml, 6230.2 mIU/ml and 2181.l mIU/ml for 5, 2.5 and 1.25 mcg
doses, respectively. Geometric mean titers at 12 months were 3481.6 mIU/ml,
3051.5 mIU/ml and 819.2 mIU/m l for 5, 2.5 and 1.25 mcg doses, respectively.
Figure 1 presents confidence limits on the mean predicted titer at each dose
level for a one year old and a 9 year old.
Serologic data from children vaccinated with 5 mcg doses in study 865 were
sumarized but not included in the statistical analysis. Twenty-one of these
children received three injections at O and 1 and 6 months, while ninety-six
received two injections given at O and 1 month. Table 1 illustrates that
seroconversion rates at 6 months were 98% and 85% for a cutoff of S/N >2.1 and
m!U/ml >10. respectively. For those children who received a third injection at
6 months. seroconversion rates increased to 100% regardless of cutoff. A large
boost in titer was seen among those children who received the third injection
00646
(Table 3). Geometric mean titers at 8 months were 1894.81 mIU/ml and 84.50
m!U/ml for those in the three and two inmunization groups, respectively.
Safety
Clinical complaints among children following 231 injections given in study 809
were available for analysis (Tables 4-6). The incidence of local ( injection
site) complaints, of systemic complaints, of either local or systemic complaints
and of fever (oral temperature of 100°F or more ) were analyzed. The incidence
at each dose was defined as the number of subjects with the comp 1a int at any
time during the 5 day period following vaccination divided by the number
reporting; while the total was the sum over the three injections divided by the
number of injections with follow-up (Table 4). The frequency of systemic
complaints is shown in Tables 5 and 6. All compla i nts were minimal and
transient. The statistical methods used in this analysis are shown in Appendix
1.
None of the incidences of complaints were found to be a function of log dose
level. Children who received 2.5 mcg of vaccine tended to report fewer
complaints with each dose level. However, the incidences of local and systemic
complaints were highest aft er the second injection in children who received 5
mcg of vacc ine. Over all doses and dose level s, fever (oral temperature of
100°F or greater) occurred after 12.7% (24/189) of injections with follow-up.
Injection site complaints (15/229, 2.2%) reported were soreness, tenderness, or
ecchymosis, while systemic complaints most often were respiratory (18/229
injections, 3.5% ) or fatigue (7/ 229 injections, 3.1%).
Clinical data f rom children fol l owing 282 injections of 5 mcg doses in study 865
were sunmarized but not included in the statistical analysis (Tables 4 and 7).
Fever was reported after 10 .3% (29/282) of injections with follow-up. The only
injection site complaint was soreness (1.8%), while systemic complaints were
mainly digestive (2.5%) or respiratory (1.4%).
The vaccine has been well tolerated in this population. No serious react i ons
have been reported.
In surrmary, the vaccine has been well tolerated by infants and children.
Although seroconversion rates were excellent with all dosages of vaccine
utilized, the highest antibody titers were obtained with the 5 mcg dose of
vaccine.
Ft GURE I
Confidence Intervals on lhe Predicted Mean at '1/8 Months

By Age and Dose in Hedthy Children
Who Received Yeast Recombinant Hepatitis 8 Vaccine
Prepared by the (b) (4) Method
162755
-I
- ~98/4
22026
8103
c
Q)
2981
l/l
C
0
0.. 1097
Vl
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148
AGE 1 9 1 9 1 9
1.25 Meg 2 .5 Meg 5 Meg

0
0
DOSE 0-
...,
0
Table I
Percent Seroconversion (Proportion) by Dose in Healthy Chi ldren Who

Received Yeast Recombinant Hepatftf~ 8 Vaccine
Month 1 Honth 3 Month 6 Month 7/ 8 Month I 2
Study
No. Dose S/N >2. I mlU/■ 1 >10 S/N l2. I 11IU/11lllO S/l l2 . t 1111U/ml llO S/N ~2. 1 a JU/ml >10 S/N l2.1 111IU/ml >10
609 1. 25 40.0 (10/25) 8.0 ( 2/25 ) 100 ,0 ( 1/1 ) 85.7 ( 6/7 ) 100.0 (21/21) 90 .5 (19/21) 100.0 ( 17/17) 100.0 (17/17) 100.0 ( 9/9 ) 100.0 { 9/ 9)
809 2.50 44. 4 ( 12/27 ) 22.2 ( 6/27) 100.0 ( 17/17 ) 82.4 ( 14/17 ) 96.4 ( 27/28) 92.9 (26/28) 100. 0 (21/21) 100.0 (21/21 ) 100.0 (19/19) 100.0 ( 19/ 19)
809 s.o 47. 0 ( 9/19 ) 16.0 ( 3/19) 100,0 ( 10/10 ) 100. 0 ( 10/10 ) 100.0 (19/19) 100.0 (26/28) 100. 0 ( 14/14) 100 .0 (14/14) 100,0 (13/13) 100.0 (13/ 13)
865 5.0 36. 6 (52/142) 13.4 119/142) 94 .0 ( 110/11 7) BJ. 2 (95/ ll 7) 97.9 (94/96) 85.4 (82/96) 100.0 (21/21)* 100.0 (Zl/21)*
95.8 (23/24)** 87.5 (Zl/24) ..
- -
• Received 1 3rd inject ion 1t 6 1110nths.

•• Otd not receive• third Injection at 6 -,nths .
0
0
0-
l::
0:,
Tablt 2
Percent Seroconvers1on (Proportion) By Dose and Age Group in ttealthy Children

Who Received Yeast RecOll'bl~ant Hepat1t1s 8 Vaccine (Study 809)
Month I Month 3 Month 6 Month 719•

Dose Age Group
(HCG) (Years) S/N 12.1 ■ IU/1111 110 S/N 12.1 11IU/11l )10 S/N 12.1 ■ IU/111 1.10 S/N 12,1 11IU/ ml 110
I. 25 (z4 41.7 (5/12) 8.3 (1/12~ 100. 0 l3/3~ 100.0 (3/3) 100.0 ( 8/8 l 100.0 ( 8/8 ) 100.0 ( 111 l 100.0 ( 7/7)
l. 25 !i • lZ 38.S (S/13) 7 .7 (l/13 100,0 4/4 7f>.O (3/4) 100.0 (13/13) 84.6 (11/13) 100. 0 ( 10/10) 100.0 ( 10/10)
2.50
2.50
<•4
5 • 12
64 .3 f9/14l
2~. l 3/13
35.7 15114
7.7 1/13 l 100.019/9J
100.0 8/8
100.0 f9/9!
62 . 5 5/8
100.0
92.3
f12/13
15/151 93. 3 p411sl
92.3 12/13
100.0 p21121
100.0 9/9
100. 0 p2112)
100.0 9/9 )
5.0
5.00
<•4
5 - 12
54 .5 i6/lll
37 .5 3/8
18.2 (2/11)
12.5 (1/8 )
100.0 (6/6)
100.0 (4/4)
100.0 (6/6)
100.0 (4/4)
100.0 (11/11)
100.0 ( 8/8 )
100.0 (11/111
100.0 ( 8/8
100.0 ( 8/8)
100.0 ( 6/6 l
100.0 ( 8/8 )
100.0 ( 6/ 6 )
• Month 7/8 included 9 month dat• when 7 or 8 111011th was not av•tlable .
0
0
0-
c
,Q
Tab le J
Geonetric Mean Titers py Dose in Heal thy Children Who

Received Yeas t R@conbinant Hepat i t i s B Vaccine
Month l Month 3 Month 6 Month 7/ 8 Month 12

GMT (111U/11l) GIil (mlU/111) &NT (111U/11l) 00 (11IU/•l) GMT ( .. IU/ 1111)
Responders Responders Responders Responders Responders
Study All S/N 11JU/111l Al I S/N 11IU/•l All S/N 11IU/11I All S/ N 111U/11l All S/N ,nJU/ nl
Dose Yacc . >2. I >10 Yacc. >2. 1 Vacc.
I N
" ->10 N >2. 1 -) 10 N Yacc . >2.1 >10 N Vacc . >2 . I >IO
809 1.25 25 1.2 7.4 69.7 7 SZ.7 52.7 77 . 5 Zl 75.9 75.9 100.7 14 2181. I 2181. I 2181 . 1 9 819. 2 819. 2 819. 2
809 2.50 27 1.9 11.4 28.9 17 86 . 9 86 .9 144 . 7 28 125.2 156.5 175. 7 21 6230. 2 6230.2 6230. 2 19 3051. 5 ~051.5 JO!il .5
809 5. 0 19 2.0 11. 7 63 .9 10 189 . J 189.3 189 . 3 19 308.4 308.4 308. 4 14 15965 . 5 15965 . 5 15965 . 5 13 3481.6 3481 . 6 3481 . 6
665 5.0 142 0.9 8.8 26. l 117 44.7 63.5 81. 2 96 59.4 74.7 98.6 21 1894 ,8* 1894 .8* 1894 .8*
24 84 . 5.. 107 .9.. 144.9**
• Received a th i rd Injection at 6 110nths .

.. Did not recehe • third Injection at 6 110nths.
0
0
,.,,fT'
0
00b51
Table 4
Percent (Proportion) of Healthy Children (Ages 1·12) with

Clinical Complaints During a 5-Day Period Following Vaccination
With Yeast Recombinant Hepatitis B Vaccine
Study 809
First Second Third All

Txee of Com~laint Inj ection Injection Injection Injections
1.25 mcg of Vaccine
Local (Injection Site) 0 (0/26) 0 (0/26) 4.0 (1/25) 1.3 ( 1/77)
Systemic 19.2 (5/26) 11.5 (3/26) 12.0 (3/25) 14 .3 ( 11/77)
Any Local or Systemic 19 .2 ( 5/26) 11.5 (3/26) 16.0 (4/25) 15.6 ( 12/77)
Fever ~100° F (Oral) 20.0 (4/20) 11. l (2/18) 7.1 (1/14) 13.5 ( 7/52)
2.5 mcg of Vaccine

local (Injection Site) 6.3 (2/32) 3.2 ( 1/31) 0 (0/30) 3.2 ( 3/93)
Systemic 18.8 (6/32) 12.6 (4/31) 6.7 ( 2/30) 12.9 (12/93)
Any Local or Systemic 21.9 (7/32) 16.l (5/31) 6.7 (2/30) 15.1 (14/93)
Fever 2_100° F (Oral) 13.3 (4/30) ll.5 (3/26) 11. 5 (3/26) 12.2 (10/82)
5 mcg of Vaccine
local (Injection Site) 0 (0/21) 5.6 ( 1/18) 0 (0/20) 1.7 ( 1/59}
Systemic 14.3 (3/21) 22.2 (4/18) 5.0 (1/20~ 13.6 (8/59)
Any Local or Systemic 14.3 (3/21) 27.8 (5/18) 5.0 (1/20 15.3 (9/59)
Fever~ 100° F (Oral) 19.1 (4/21) 6.3 (1/16) 11.1 ( 2/18) 12. 7 ( 7I 55)
Study 865
First Second Third All

Type of Complaint Injection Injection Injection Injections
5 mcg of Vaccine
Local (Injection Site) 2.1 ( 3/141) 1.7 ( 2/116) 0 (0/25) 1.8 ( 5/282)
Systemic 5.7 ( 8/141) 4.3 ( 5/116) 4.0 (1/25) 5.j (14/282)
Any Local or Systemic 7.8 (11/141) 5.0 ( 7/116) 4.0 (1/25) 6. ( 19/282)
Fever 2_ 100°F {Ora 1) 9.9 (14/141) 12.l ( 14/ 116) 4. 0 (1/25) 10.3 (29/282)
006r;2
Table 5
Frequency of Systemic Complaints by Body System Occurring

Within 5 Days Among Healthy Children Following 231 Injections of
Study: 809
Frequency as%
BodX sxstem/Comelaint (Number)
Whole Body/General 5 (12~
Fatigue/Weakness 3 (7)
Headache 0.8 (2)
Sweating 0.4 (1)
Bruise from venipuncture 0.4 (1)
Illness, NOS 0.4 (1)
Digestive 4 (10)
Diarrhea 2 (5)
Vomiting 1.3 (3)
Diminished Appetite 0.4 (1~
Loose Stool 0.4 (1
Nausea 0.4 (1)
Teething 0.4 (1)
Respiratory 4 (9)
Upper Respiratory Infection, NOS 2.6 ( 6)
Pharyngitis 0.8 (2)
Rhinitis 0.8 (2)
Cough 0.4 ( 1)
Croup 0.4 ( 1)
Psychiatric/Behavioral 2 (5)
Irritability 1. 7 (4)
Insomnia/Disturbed Sleep 0.4 (1)
Infectious Syndromes 2 (4~

Viral Infection 1.7 (4)
In tegumen ta ry 1 (3)
Papul ar rash 0.8 (2)
Rash, NOS 0.4 (1)
Urt i ca ri a/Hives 0.4 (1)
Organs of Special Sense 0.4 ( 1)

Otitis Media 0.4 ( 1)
00653
Table 6
Percentage (Number) of Healthy Chi l dren with Speci fic

Systemic Complaints During a 5 Day Period Following
231 Injections of Yeast Recombinant Hepatitis B Vaccine
Study: 809
Complaint Frequency 1 - 3%
Fatigue/Weakness 3 ( 7)
Upper Respiratory Infection NOS 2.6 (6)
Diarrhea 2 (5)
Vomiting 1.3 (3)
Irritability 1.7 (4)
Viral Infection 1.7 (4)
Complaint Frequency 0.5 - 0.97%

Headache 0.8 (2)
Pharyngitis 0.8 (2)
Rhinitis 0.8 (2)
Papular Rash 0.8 (2)
Complaint Frequency 0.1 - 0.49%

Sweating 0.4 ( 1)
Bruise from venipuncture 0.4 (1)
I 11 ness, NOS 0.4 (1)
Diminished Appetite 0.4 (1)
Loose Stool 0.4 (1)
Nausea 0.4 (1)
Teething 0.4 ( 1)
Cough 0.4 (1)
Croup 0.4 {1)
Insomnia/Disturbed Sleep 0.4 (1)
Rash, NOS 0.4 (1)
Urticaria/Hives 0.4 (1)
Otitis Media 0.4 (l )
0065Q
Table 7
Frequency of Systemic Complaints by Body System Occurring

Within 5 Days Among Healthy Chi l dren Following 282 Injections of
Study: 865
Frequency
Body System # Complaints as%
Digestive 7 2.5
Respiratory 4 1.4
Whole Body 3 1.1

00655
A P P E NOI X 1
S T AT I S T I CA L M E T HO OS
31241/11
l /21 /86
00656
All tests of significance were two-sided at 0.05 significance level .
A. Clinical Comp la ints

1. The incidence of the vari ous c l inical complaints in dialysis
patients on the t hree dose regimen, healthy teenagers and healthy
child ren were evaluated as a function of log dose level using the
Mantel-Haenszel Test 1 for trend.
2. All other differences in the inc idences of the various clinica l
complaints In dialysis patients due to dose level or regimen and
in health care personnel receiving vaccine from consistency lots
were assessed by the Likelihood Ratio Chi-Square .
adults, healthy teenagers and health~ children was analyzed over
studies using the Mantel Haenszel Test for trend.
2. Differences in seroconversion rates in healthy adults due to age
or sex were eva l uated over studies using the Mantel Haenszel
3. Differences in seroconversion rates due to age in healthy
children, dose level in dialysis patients, and vaccine lot in
Chi-Square.

The effect of age, sex 1 1ot (cons istency lots only in Study 880) , or
dose 1eve1 (al l other studies) in health care personnel and other
age in hea l thy children, and of dose level and regimen in dialysis
model . Subjects who were negative for antibody to hepatitis B surface
antigen were assigned a titer of 0.3 mIU/ml in the analysis.
REFERENCE
1. Tarone RE, Ware J: On Distribution-Free Tests for Equality of

Survival Distributions. B1ometrika 64: 156-160, 1977.
31241/12
00657
HEA LTHY CHILDREN
Study 809 - Philadelphia. PA - Dr. S. Plotkin and Dr. S. Starr

Healthy adults and children (1-11 years of age), who are seronegative for
hepatitis 8 virus markers, are enrolled in Study 809. Healthy children
receive either 1.25 mcg or 2.5 mcg injections of vaccine lot C-K723 or 2.5 mcg
or 5 mcg injections of lot C-K444. All injections are administered at 0, 1,
and 6 months.
Twenty-six children have received two 1.25 mcg inject ions of vaccine and 25 of
subjects seroconverted (SIN ~2.1) and deve loped protective levels of anti-HBs
(mIU/ml ~10). The GPIT for all vaccinees was 2181.1 mIU/ml.
Thirty- two children have received two 2.5 mcg injections of vaccine and 30 of
vaccinees seroconverted (S/N ~2.1) and developed protective levels of anti-HBs
(mIU/ml ~10). The GMT for all vaccinees was 6230.2 mIU/ml .
In the 5 mcg dose regimen, 22 children have received two injections of vaccine
and 21 of these have received the third injection . At 7/8 months, 100%
(14/14) of the children seroconverted (S/N ~2.1) and developed protective
levels of anti-HBs (mIU/ml ~10). The GMT for all vaccinees was 15965.5 mIU/ml.
Anti-HBs titers were higher in the children who received 5 111eg injections than
in the children who received 1 . 25 mcg or 2.5 mcg injections of vaccine.
Study 865 - Hone Kong - Dr. E. K. Yeoh

Healthy infants and children, ages 3 months through 1 1 years, who are negative
for hepatitis 8 serolog1c markers are enrolled in Study 865. The children are
assigned to receive 5 mcg injections of vaccine lot C-IC732 at O and l months
or at 0, l, and 6 months.
Ninety children, in the two injection regimen, have received one 5 mcg
injection of vaccine and 70 of these have received the second injection. At 6
months, 98% (49/50) of the children seroconverted (S/N ~2.1) for anti-HBs and
94% (47/50) developed protective levels of antibody (mIU/ml ~10). The GMT for
a 11 vaccinees at that time was 81. 6 mlU/ml and 102. 5 for responders (mIU/ml
>10) . At 8 months, 87.5% (21/24) of the vaccinees were positive for anti-HBs
(mlU/ml ~10) wi th a GMT of 145.0 mIU/ml.
Eighty-eight children, in the three injection reg imen, have received the first
5 mcg injection of vaccine. Seventy-two and 46 subjects have been
administered the second and third injections, respectively. At 8 months, 100%
31581/1
l /21 /86
00058
Study 865 - Hone Kong - Or. E. K. Yeoh (Cont.)
(21/21) seroconverted (S/N ~2.1) and developed protective levels of anti-HBs

(mIU/ml ~10). The GMT for all vac cinees as 1894 . 8 mI U/ml .
No serious or alarming adverse reactions attribut able to vaccine have been

reported . Vaccination and follow-up continue in progress.
Study 891 - China - Or . Z. H. Hu
The study population consists of healthy adults and healthy children who are
negative for hepatitis B serologic markers . Healthy adults receive either 10
mcg injections of yeast recombinant vaccine or 20 rncg injections of
plasma-derived vaccine . Healthy children received either 5 racg injections of
yeast recombinant vaccine or 10 mcg injections of plasma-derived vaccine. All
injections are administered at O. 1, and 6 months . Yeast recombinant vaccine
lot C-K564 and plasma-derived vaccine l ot 0027L are being utilized .
Twenty -fi ve children have received the f i rst injection of yeast recombinant
vaccine and 25 have received t he first injection of plasma-derived vaccine.
None have received second or third injections of vaccine. Serology data are
not presently available. No serious or alarming adverse events attributable
to vac ci ne have been reported. vaccination and follow-up continues in
progress .
31581/2
1 /21 /86
<»
0
\I:)
OObSQ
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepatitis 8

Vaccine. Study 809
PURPOSE: To evaluate ant i body and clinical responses to

various doses of vaccine in the following
initially serone_gative populations:
1. Healthy Children (l-11 years of age)
2. Healthy Adults
Lot# 972/C-K444 (10 mcg HBsAg/ml)
985/C-K732 ( 5 mcg HBsAg/ml)
PRINCIPAL Ors . Stanley Plotkin and Stuart Starr

INVESTIGATOR: Division of Prevent1ve Medicine
34th Street -and Civic Center Blvd.
Phi"ladelph ia, PA 19104
STUDY LOCATIONS: The Pediatric Medical Associates

420 Townsh i p Line Road
Havertown. PA 19083
George A. Starkweather, M.O.
1001 Pennsylvania Avenue
Havertown, PA 19083
STUDY POPULATION: The study population consists of healthy children

(ages 1-11 years) and healthy adults who are
negative for HBsAg. anti-HBc. and anti-HBs . have a
normal ALT level and have not previously received
25281/1
12/31 /85
00&60
Study 809
PROCEDURE: Children in the study receive a 0.5 ml (5 mcg HBsAg) or

a 0.25 ml (2.5 mcg HBsAg) intramuscular inject ion of lot
# 972/C-l<444 vaccine at 0, l and 6 months .QL a 0.5 ml
(2.5 mcg HBsAg) or 0.25 ml (1.25 mcg HBsAg) injection of
lot # 985/C-K732 vaccine according to the same ti(!le
schedule. Adults receive a 1 .0 ml (10 mcg HBsAg)
intramuscular injection of lot I 972/C-1<444 vaccine at
0, 1 and 6 months . Vaccine recipients (or the parent or
guardian in the case of a minor) are asked to record
their temperature daily for five days after each
injection of vaccine and to record any local or systemic
A blood specimen {10-15 ml) is obtained from each
prospective vaccine recipient one to two weeks before
the first. vaccination. Post-vaccination bleedings are
obtained at 1, 3, 7 and 12 months from some of the
children and at 2, 6, 8 and 12 months from others.
Post-vaccination bleedings are obtained from adult
vaccine recipients at 1, 2, 3, 6, 8, 12 and 24 months.
The samples are assayed for H6sAg, ant1-H8c, ant1-HBs,
and ALT. Samples may also be tested for yeast antibody
and those with an ant i-HBs titer ~ 25 mIU/ml may be
tested for the proportions of anti-i and anti-d act i vity.
RESULTS: HEALTHY CHILDREN:

1.25 mcg Lot I 985/C-K732 at 0, 1, and 6 months
5 mcg lot I 912/C-K444 at o. 1, and 6 months
Injection No.
Dose Level _1_ __2_ __3_
1.25mcg 26 26 25
2.5 mcg 32 32 30
5 mcg 22 22 21.
25281/2
12/31 /85
0 0 661
Study 809
RESULTS : (Cont.) 2. Serolo9ic Results:

Serologic data are available for 14, 22, and · 14
participants at 7/8 months, who received 1.25 mcg.
2 .5 mcg and 5 mcg i nj ecti ons of vaccine.
respective ly. One hundred percent of the subjects
(all dose levels) seroconverted (S/N ~2 . 1) and
developed protective levels of anti-H8s (mIU/ml
~10) at that time . Anti-HBs responses and GMTs
for 7/8 month data are sunrnarized in the following
table.
- -- - Giff (111IU/ m1} - - -

Dose - \ vith Anti-4es - All - - - Responders - -
Level SIN'::: 2. 1 mlU/ 11I ~ 10 Vacci~s S/N '::: 2. l mlU/ml ~ 10
l . 25 mcg 100(14/14) 100 (14/ 14) 2181. 1 2 181. 1 2181. l

2 . 5 mcg 100(21121) 100 (21/ 2 1) 6230.2 6230.2 6230.2
5 mcg 100(14/14) 100 ( 14/ 14) 15965 . 5 15965.5 15965.S

months, 100% ( 9/ 9), 95% ( 18/ 19) and 100% (13/13)
were positive for anti-HBs {mIU/ ml ~10) from dose
level 1.25 mcg, 2.5 mcg and 5 . 0 mcg,
respective ly. The GMTs for all vaccinees f rom
these dose levels were 819 . 2, 3051 .5, and 3481 . 6
mlU/ ml, respectively.
Refer to Table l for anti -HBs responses and GMTs
for other time intervals .
Clinical fol low- up data are ava i lable for at least
25, 30, and 18 participants, after each injection,
in the 1.25 mcg, 2.5 mcg, and 5 mcg dose level ,
respectively . The overa 11 frequenc i es of
complaints follow .
25281 / 3
12/ 31 / 85
00662
Study 809
RESULTS (CONT . ):
Type of Dose Freouencv in I bv Iniection No.

Complaint Level 1 2 3
Injection 1.25 mcg 0(0/26) 0(0/26) 4(1/25)

Site 2.5 mcg 6(2/32) 3(1/31) 0(0/30)
5.0 mcg 0(0/21) 6(1/18) 0(0/20)
Systemic l. 25 mcg 19(5/26) 12(3/2£>) 12(3/25)

2.5 mcg 19(6/32) 13(4/31) 7(2/30)
5 . 0 mcg 14(3/21) 22(4/18) 5( 1/20)

specific complaints by injection number and dose
level. Maximum temperature data are provided 1n
Tables 5 through 7.
There have been no serious or alarming reactions
attributab l e to vaccine.
25281/4
12/31 /85
Table I
Antibody Respoo~ llnlong Healthy Children fol1011ing Vaccination with

1.25, 2 .S, or S incg Injections of Ye.st Recait>lnant Hepatit is B Vaccine
lot I 972/C-Kffl and 985/C-1<732 at O, 1, and 6 flonths
1 .25 IIIC!J 2.S mc:9 S mcg

\ with Anti--HBs QIT {111IU/■l l \ with Anti--tBs GMT ~•IU/11tl 2 \ with Ant i--HBs GMT (mIU/111 l
Resoonders Resoonders Resoonders
Ti111e 11IUl•l All IBIU/1111 11IU/111l All ■IIJ/lnl •IU/111 All •IUl•l
(MM . ) S~2. 1 ~ 10 Vaccinees S/~2. 1 ~ 10 S~2. 1 ~ 10 Vaccinees S/~2. 1 ~ 10 S/~2 . 1 ~ 10 Vaccinees S/~2. 1 > 10
40 8 1.2 7.4 69. 7 44 22 1.9 11.4 28.9 47 16 2 .0 11 . 7 63 .9

(10/25) (2/25) (12/27) (6/21) (9/19) (3/19)
2 92 58 26 .2 36.0 129.2 88 63 37.8 75 .S 236.4 100 61 23. 7 23 . 7 43 . S

(11/12) (1/12) (118) (S/8) (6/6) (4/6)
3 100 86 52 . 7 52.1 17 . 5 100 82 86.9 86.9 144. 7 100 100 189. 3 189 .3 189 . 3
(1/1) (6/7) (11/11) (14/11) (10/10) (10/10)
100 90 75 . 9 75.9 100. 7 96 93 125.2 156. S 175. 7 100 100 300.4 308.4 300. 4
(21/21) (19/21) (21/28) (26/28) (19/19) (19/19)
118 100 100 2181. 1 2181. I 2181. l 100 100 6230.2 6230. 2 6230. 2 100 100 15965. 5 15965 .5 15965 . S
(14/14) (14/14) (21/21) (21/21) (14/14) (14/14)
12 100 100 819.2 819.Z 8 19 . 2 100 95 3051.5 3051 . 5 4M. 1 100 100 3481.6 3481.ti 3481.6
(9/9) (9/9) (19/19) (18/19) (13/13) (13/13)
25281/S
12/31/ 8S
Tab le 2
PATIENT COUNT CLINICAL CClf1PLAINT5
AECOt18INAHT HEPUITJS 8 VACCIIIE
STUOY 0 609
TRE.ATt1ENT
LOT HUMBER Cl<73t
DOSE 1.25 t1CG
PATIENT CL.Ass : HEALTHY CHILDREN
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCIIIEES ( 26 PATIENTS) - DOSE 1 I
1I ----------------------------------------------------------------------------I
DAYS POST VACCINATION I N\.tlBER
CLINICAL
COt1PLUNT5
l----------------------------------------------------------------------------1
I O I 1 I Z I l I 4' I 5 I
MITH
I COMPLAINTS
·································••l••······••l••······•·l••······••l••······••l••······••l••····••N•l••·······•l••••NNNINI
-----------------------------------l----------l----------l----------l
s r snt11c I l I Z I l I
----------l----------l----------l----------l-----------
3 I 3 I Z I I 5
f I 3 . 6 ;: ) I I 7 , 7;0 I I 3 . CliO I I 11.sr. , I I u .sr. , I I 7 . 7r. ) I I I 19.ZX I
----------------------------------- --------------------- ------------------------------------------------------------------
MHOLE BOOY/GEHER.AL l 0 0 0 0 0 l
J . 8 i0 o . o :o 0.0%I o. or. 1 0 . 0½ 1 o . o :o 3. 6% 1
FATIGUE/WEAKNESS 1 0 0 0 0 0 1
3, OY. I o . or. , O. OXI 0 . 0 %1 0. 0% 1 O . OX I 3. CIX I
INFECTIOUS SYNDR01ES 0 0 0 0 1 0 l
I O . OY. I O. OiO O. OX I O. OXI 3 , 8½ 1 O . OiO 3 . 8½1
VIRAL I NFECTIOH, NOS 0

0 . 01. I
0
0.01.1 •
O. OX I
0
0.0%)
l
3 .8½ 1
0
0 . 0 %)
1
3 . 8Z I
INTEGUNEHTARY SYSTEn 0 0 I 0 1 1 l
0. 01. I 0.01. 1 0. OX I 0 . OZ I 3 . 8½ I 3 . 8 XI 3 .8X I
PAPULAR A.ASH 0 0 0 0 l 1 l
0 . OY. I 0 . 0 ½) O.OZ I 0.0%) J . 8%1 3 .81/. 1 3.8X I
RESPIRATOIIY 0 0 0 1 l l l
O. OX I I 0 . 0½) 0 . 0%) l . 8 :0 l . e:o 3.8%) 3 . 8 1/. I
UPPER RESPI RATORT I NFECT., NOS 0 0 0 1 1 1 1

O. 0% I 0 . 0%1 0 . 0%I l. 8% 1 3 .8½ I 3 . 8 7. 1 3 . 8 ?. I
COUGH 0 0 0 1 0 0 1
( 0 . 0% I 0 . 0%1 0 . 0%) 3 . CIY- 1 0. OY. I I 0.0%1 J . 6XI
DI GESTIVE SYSTEN 0 l l 1 l 0 1
O. OX I 3 . 8iU 3 . 8 XI 3.8XI 3 . 8½ I 0 . 0 ½1 3.8%I
DIARRHEA 0
0.0%)
1
3.8%)
0
0 . OX I
0
O. OXI
•
O. OX I
0
0 . 0 ½1
1
3 .6X I
0
0
0-
0-
~
•
Table 2 (cont)
PATIENT COUNT CLIHlCAL COMPLAINTS
IUCOll8IIIAHT HEPATITIS D VACCINE
STUDY 0609
TREATHENT
LOT NUt1BER C~73~
DOSE 1 .25 11CG
PATIENT CLASS: HEALTHY OIILDREH
f TOTAL VACCitlEES ( 26 PATIENTS) - 00S£ l I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I tMeER
CLINICAL
C011PUINTS
l----------------------------------------------------------------------------1
I O I l I 2 I l I 4 I 5 I WITH
ICOMPLAINTS
•••••••••• •••••••••• •••••••••• •••••••••• •••••••••• •••••••••• •••••••••• ••••••••••
DIMINISHED APPETITE 0 l l l l 0 l
0.0X) 3.8XI 3.8XI J.8iO 3.8i0 0.0XI J.8iO
MGANS OF SPECIAL SENSE 0 0 0 1 0 0 1
o. ox) 0 . 01.1 0. 0XJ J.8XI o. ox' 0.01. 1 3. 81.)
OTITIS t1EDIA 0 0 0 1 0 0 1
I 0 . 0Y. I I 0 . 0Y. I ( 0 . 0Y. I ( l .8 Y. I ( 0 . 0%1 ( o.o;o ( 3. 8i! I
PSYCHIATRIC/ BEHAVIORAL 0 l l 1 0 0 2
O. 01. I 3.81/. 1 3,8i! I 3.81. 1 0. OX I 0.01. 1 7. 71. I
l
IRRITABILITY O I O l l O 0 1
0.07. J f I 0.07.) 3,87. J J.87.J I 0.07. J 0.07. 1 3.8iO
I
INSOttlU/OISTURBED SLEEP O I l O O O O 1
I 0.01.) I I 3.81/.I I o.o;o ( O.0iO I 0.0%) ( o.o:o I ( J . 8i( )
-----------------------------------1----------I----------I----------I----------I ---------- ----------1----------1-----------
PERSONS WITH COHPUINTS I 1 I Z I l I 3 I J Z I I S
I I J.87. J I I 7.71. l I I 3. 8 XJ I ( 11.s1. 1 I I 11,5%1 I 7.71. I I I ( 19.2% 1
-----------------------------------1---------- I----------I---------- I---------- I---------- I----------I----------I-----------
PERSONS MITH NO Cot1PLAIHTS I 25 I 24 I 25 I 23 I 23 I 24 I I 21
I I 96.2XJ I I 92.JX I I I 96.21.J I I 88. 51. J I I 88.SXJ I I 92 . J XI I I I 80.8Xl
-----------------------------------1----------l----------l----------l----------l----------l----------l----------1
PERSONs MITH HO DATA I o I o I o I o I o I o I I-----------
o
I I 0 . 0Y.I I I 0 . 01/.I I I 0 . 0 i! I I t O. 0Y. I I I 0 . 01/. 1 I I 0 .01/.1 I I C 0.0i! )
Table 2 (cont)
PATIENT. COUNT CLINICAL COMPLAINTS
RECot'BIHANT HEPATITIS B VACCINE
STUDY 0609
TREAlMEHT
LOT H.IMeER CK73Z
OOSE 1.25 MC6
PAJIEHT CLASS: HEALTHY CHILDREN
I TOTAL VACCIHEES C 26 PATIENTS) - OOSE 2 I

1----------------------------------------------------------------------------I
CLINICAL
COMPLAINTS
l----------------------------·-----------------------------------------------1
I O I l I 2 I l I 4 I 5 I
WITH
ICONPLAIHTS
•••••••••••••••••••••••••••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
-----------------------------------lI ----------
sysnt11c z I
l----------t------·---l----------l----------l----------l----------l-----------
z I t I 1 I z I 2 I I l
I c 1.n, I 1 7. no I c 7.no I c 3.ex, I t 1 . 1x1 I c 7. 7?.1 I I c 11.sx,
WHOLE BODY/GENERAL 0 0 0 D 1 0 1
0. ox) O.Ol.l 0. Ol. ) O. Ol. ) l.8l.l O.OXI 3 . 8 i0
SWEATING 0 0 0 0 1 0 l
0. ox ) 0 . 01/.I 0 . 01/. ) 0 . 01/. ) 3 .81/.) 0.01/. I 3 . 8 i0
FATIGUE/WEAKtlESS 0 0 0 0 l 0 l
0 . 01/. ) 0 . OX I 0. 01/.) 0 .ox I ] .8X I ( 0 . 01/. I ( ] . 81/.)
RESPlRATOR T 1 1 l 1 1 l 1
3.8l0 3 .8%1 3 . &X I 3.8%) ( 3 .8%) ( 3.8%1 ( 3.81/. )
RHINITIS 0 0 0 1 1 0 1
0 . 0%) 0 .0%1 0 . t%) 3.8%) 3 .8X I 0.0%1 3 . 8 %)
PHARYNGITIS (SORE THROAT) l

:S . 8 %)
1
1 . ex 1 •
o. ,x)
1
3 ,8% )
0
0.0%)
0
0 . 0 %1
1
3 .81/.1
UPPER RESPIRATORY INFECT., HOS 0 0 0 0 l 1

o. o;o 0 .0% I 1.a;o 0 .0% ) ( 0.0%1 3 .8%1 3.81/. )
DIGESTIVE SYSTEM 1 1 l 0 0 l 1
:s. 8 l. ) 3 .8l.) 3.8i0 0 . Ol. ) a.ox, 3.8Y. I 3 . Bl. )
DIARRHEA 1 1 l 0 0 1 l
:s. 8 l. , 3.8X l 3 .el. I 0 . ox l 0 . Ol. I 3 .8Xl 3 .8l. )
PSYCHIATRIC/8EHAVIORAL l 1 l 0 0 0 1
:S . 8 %) 3. 81. 1 1.ex , 0.01. ) 0 . 01.1 0 . 01.1 3 . 8 %)
IIIRITABillTY 1 1 l 0 0 0 1
3 . 8 XJ 3 .81/. I 3.81. I O. Ol. I 0 .Ol. I O.OXI 3 . 81/. ) 0
0
c,,.
C1'-
C1'-
'fable 2 (cont)
RECOl'SINAHT HEPATITIS B VACCINE
ST\JOY 0609
TREATl1ENT
LOT HUNeER CK732
DOSE 1.25 HCG
PATIENT CLASS: HEALTHY CHILDREN
-------------------•----•------••---------------------------------L---------------------------------------------------------
I TOTAL VACCINEES C 26 PATIEIITSI - DOSE 2 I
t----------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUHBER
1----------------------------------------------------------------------------I
CLINICAL
COttPUINTS
................................... I
, I>
.......... I l
,
.......... I Z
.......... ,
,I..........
l I <t
.......... I 5
.......... I
,
WITH
.......... ICOMPLAJITTS
.........•
-----------------------------------1 ----------I---------- I---------- I---------- I----------I---------- I---------- I-----------
, , ,
PERSONS WITtt COIIPLAIHTS I 2 I 2 I 2 I l I 2 I 2 I I 3
I 1 1.1r.1 I 1 7.n> I 1 1 .1r. 1 I 1 :s . e ;,: 1 I t 7.7%> I 1 1.1x , I I I i1.sx ,
-----------------------------------1
PERSONS WITH NO COl1PLAIHTS I
----------l----------t----------
24 I 24 I 24
l----------
I 25
l----------
I 24
l----------
I 24
l----------l-----------
I I 23
f I 9 2. 37. I I C 'IZ • 3% l f I 92. 3;,:) I I 91> . z;,: ) I I 92 . 3;,: I I I 92. 3;,: ) I I C 68. sr. )
-----------------------------------1----------I----------I-----
PERSDHS WITH HO DUA I O I O I
·----l----------1----------1----------1----------I-----------
O I O I 9 I O I I 0
I l o. oz I I c o. 0:1.1 I l o. o:o I l o. o:o I I o. 0:1. I I c o.0:1. 1 I I c · o. or. I
Ta b le 2 ( cont)
PATIENT COlMT CLINICAL COHPlAI HTS
RECOMBINANT HEPATITIS 8 VACCI NE
S TUDY 0809
TREATMENT
LOT tlllt18EIP CK732
OOSE 1.25 MC&
PATIENT CLAS'5: HEALTHY CHILDREN
-------------------------------------------------------------------------------------------------------------------·--------
J TOTAL VACCIHEES C Z5 PATIENTS I - DOSE 3 I
l----------------------------------------------------------------------------1
CLINICAL
COt1PUINTS
J----------------------------------------------------------------------------1
I O I 1 J 2 I 3 I 4 I S I
MITH
ICOHPLAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION, LOCAL IINJECT. SITE> I 1 I O I O I O I O I O I I 1
I ( 4 . 0XI I I D. OX I I l O. DX I I C O. OXI J C D. OXI I I 0 . 0 XI I I C 4 . 0XI
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l---
s ~EN£SS I l I O I O I O I o I o I I
------
l
I( 4 . 0X) I( 0 . 0 7. ) I( O.OY. ) I( O. OY. I I( 0 , 0 7. 1 I( O. OXI I I( 4 . ox ,
-----------------------------------l----------l----------l----------l----------l----------l----------l
s r sTEt1Ic I 0 I 0 I l I 2 I 3 I 0 I
----------l-----------
I 3
I c o . ox , I c o . ox , I c 4 , ox 1 I c e . o x , I c 12.ox , I , , . ox , I I 1 12 . o x1
---------------------------------------------- ------------------------------------------- ---------- ----------------------
lolfOLE BOOY/GENERAL 0 0 l 0 1 0 2
o . ox ) 0 . 0 7. I ( 4 . 07. ) 0 , 0 7.) ( 4 . 0 7. J C 0 . 0 )0 ( ll . OY. I
FATIGUE/WEAKNESS 0 0 l 0 0 0 1
( O. OXI C 0 . 0%) 4 , 0%I 0 . 0 %) t o . ox ) I o.ox ) " . o x,
ILLNESS, NOS 0 0 D 0 l 0 1
o.o;o 0.01/. ) 0 . 01/. ) 0 . 0 1/. ) tt . o;o 8 . 0 7. I lt.07. 1
DIGESTIVE SYSTEM 0 0 0 2 2 0 2
0 . 0 7. ) 0 . 07. I 0 . 07. I 8 . 01/.) 8 . 07. ) O. OXI e . ox ,
VOHITING 0 0 0 1 1 0 1
o . o r. , 0 . 01/. 1 0 .01/. 1 4 .07. ) 4 . 0i( ) 0 . ox I 4.0i()
LOOSE STOOL O O O 1 1 0 1
I O.OY. ) I 0 . 01/. 1 I 0 . 0½ ) I 4 . 0 7. 1 ( 4 . 0½) I O. OiO ( 4 . 0 ZI
-----------------------------------1----------I----------
PEAS ONS WITH COMPLAINl S I 1 I O
I----------
I 1 .
----------
2
t----------
I 3
1----------1----------1-----------
I O I I 4
I t 4 . 0 7. ) I C O. OX I I C 4 . 0Z I ( 8 .0XI I I 12 . 0 XI J I O. Ol. l I I ( 16.0XI
-----------------------------------1
PERSONS WITH NO COMPLAINTS I
----------I----------I----------
24 I 25 I 2ft
----------
23
1----------1
I 22 I
----------1
ZS I
---------- II-----------
21
I c 96, 0 JO I 1100 . ox 1 I c 96. o;o , ,2 . o x 1 I , ee. oY.1 I uoo . o io I I c e1t.ox 1
-----------------------------------1----------l----------l----------
PERSONS WITH NO DATA I o I o I o
l----------l----------l----------1----------1-----------
I O I o I O I I O
I I 0 . 0 7. ) I I 0 . 07. 1 I I o . or. 1 It O.OXI I C 0 . 0%) I C O. Ol. ) I I I 0 . 0%)
Table 3
PATI ENT COUNT CL I~I CAL COMPLAINTS
RECOMBINANT HEPATI TI S 8 VACCINE
STUDY 0809
TREATMENT
DO SE 2.5 MCG
PA TIENT CLASS: HEALTHY CHILDREN
TOTAL VACC INEE S ( 32 PATIENTS ) - DOSE 1
DAYS POST VACC INATI ON NUMBER

CLINICAL WITH
COMPLA INTS o I 2 I 3 I " S COMPLAI NTS
•••••••••••• ••••••••••••••••••••••• ·········· 1·········· ··········1·········· ...... ... . • •••••••••••••••••••••••••••••
REACTION, LOCAL {INJECT. SilE) 2 I 1 o I o o 0 2
c 6 . 3,,, ) I ( 3 _ 1,c,) ( o.o,c,> I c o . o,c,> < 0 . 0 %) 0 , 0,,,) 6.3%)
SORENESS
------~---1------~--- ------~---1------~---,------~--- 0 I
3 . , ,,, J I J . 1,c,) I c o . o,,, > I < o . o,c. ) I < o . me.> o . o,,, > I 3 • ' "' >
I I I I I
TENDERN ESS o I
I o I o I o o I
( 3, 1'!1,) I ( 0.0%) I ( 0.0%) I ( O . O'!f.)
0 .0%) I ( 0 , 0" ) I ( 3 , 1,c. )
----- ----- 1----------1 -- - -- - --- - 1------ ---- 1------ ---- ---------- ---------- 1I -----------
SYSTEMI C 1 I 2 I I I 0 I 2 3 6
3 . '") I ( 6 . 3%) I ( 3 . I% ) I ( 0 . 0% ) I ( 6. 3'4) 9 , 4,,, l I < 1B. 8% l
WHOLE BODY/GE NERAL 0 1 0 0 0 I I

o . o,i,) 3 . 1,C,) 0.0%) 0.0%) 0 . 0%) 3 I ,i_) 3 .1 %)
HEADACHE 0 1 0 0 0 1 I
0 , 0,,,) 3. 1%) 0 ,0,C, ) 0.0%) 0.0%) 3 , 1%) 3. I ,C, )
I NFECTIOUS SY NDROMES 0 0 1 0 2 1 3
0 , 0,,,) 0. Q,C,) 3. 1%) 0 .0%) 6 . 3,C,) 3 . 1'11) 9 . 4'11 )
0
VIRAL INFECTION, NOS 0
0 , 0,,,)
0
0.0%) 3.
I
I'll,) 0. 0,C.)
2
6 . 3Y.) 3 ,1,,, ) 3
9 . 4'lC.)
RE SPIRATORY 1 I 0 0 0 1 2
3. l'1,) 3. 1"1, ) 0. 0"1, ) 0. 0"1,) 0 . 0'4) 3 . I%) 5. J"1,)
UPPER RESP IRATORY INFECT . , NOS 1 1 0 0 0 0 I

3 , 110 3. 1%) 0.0%) 0 .0%} 0 . 0'1,) 0 , 0,,,) 3. 1%)
CROUP 0 0 0 0 0 1 I
0 , 0,,.) 0.0%) 0 . 0%) 0 .0%) 0 . 0% ) 3 . 1%) 3. 1'1, )
DI GESTIVE SYSTEM 0 I 0 0 0 0 I
0. O'JI) 3. 1%) 0.0%) 0 . 0%) 0.0%) O . O'JI) 3. 1%)
Tabl e 3 (con t)
PAT IENT COUNT CLINI CAL COMPLAI NTS
RECOMBI NANT HEPATI TI S B VACC INE
S TUDY 0009
TREATMENT
DOSE 2. 5 MCG
PATIENT CLA SS: HEALTHY CHI LDREN
TOTA L VACCI NEE S ( 32 PAT I ENTS) - DOSE 1 I

-------------------------------------------------------------------
DAYS POST VACC INA T I ON
--------- 1I NUMBER
---------- ------- -- --1! COMPWLAINT
CLINI CAL
COMPLAIN fS o
....•........•............. ........ ········•• I 2
.
1I •• ········ ..••...•.•...•.••........•... ········•·1I ••·· ····••1I ••········
J 4 5 I
I TH
S
NAUSEA o I 0 0 0 o I I
C 0.01' ) I < 3 , 11') 0 . 0 1') 0. 0 1') 0 . 0 %) ( 0. 0% ) I I ( 3 . I %)
PERSONS WITH COMPLAI NTS

----------
3
1I ----------
3 1 0 2
----------
3
1I ---------- 1-----------
I 1
C 9 . 41'> I < 9 . 41' J 3 . 11') 0. 0 %) 6 . 3 %) 9 . 4% ) I I c 21 . 9 %)
PERSONS WITH NO COMPLAI NTS
----------
29
1----------
I 29 31 32 30
- ----- -- 1------- -- 1-----------
29 I I 2s
c 9 0.61') I c 90 . 6 1' ) { 96 . 9'1, } ( 100.0%) ( 93. 8% ) < 90 . 6%) I I < 78 . 1%)
PERSONS WITH NO OATA
----------
0
1I ------ o---- -- - ------·· 1----------
c I o
----------1----------1
0 I I
-----------
o
o .01' ) I c 0 . 01' ) <. -~_. o;. J I c o.O%J 0. 0% ) I I l 0.0%)
0
0
a-
"'
0
Table 3 (co nt )
PATIENT COUNT CL INI CAL COMPLA INTS
RECOMBINANT HEPATITIS B VACC INE
STUDY 0809
TREATMENT
DOSE 2 . 5 MCG
PAT IENT CLASS: HEALTHY CHILDREN
TOTAL VACCINEES ( 32 PA T IENTS) - OOSE 2 I

------------ ----------------------------------------------------------------1
DAYS POST VACCINATION I NUMBER
CLINICAL
COMPLAINTS
----------
0
---------- ---------------------
Z I 3
---------------------
4 I 5
----------! WI TH
I COMPLAINTS
••••••••••••••••••••••••••••••••••• .................... ········•• 1••········ ········••1••··· ····· ········••1••········
I I I
RE ACTION, LOCAL (INJECT . SITE) I
3,21.) ' (
O I
0.01.) I (
3. 21, )
O
0.0%} (
O I
O.O'A,) I (
O
0 . 0%)
I ( 3.2%)
SORENESS
---------- ---------- ----------,----------
I o
----------,----------
o I o
---------- 1I -----------
'
3 . 27.) '
3.2'1C, ) (
0
0.01.) I ( 0. 0%) ( O. O'A,) I ( 0 . 0%) I ( 3.2%)
SYSTEMIC
----------
1
----------
2
----------,----------
1 I o
----------1----------
, I o
----------1-----
I
------ 'l
3 . 21,) 6 . 5"-) 3.21.> I < o.o,r,J 3.2,i,J I c 0.01.1 I c 12 .s,r,J
I I I
WHOLE BODY /GENERAL I I 0 0 0 I 0 I 0
3 .2%) I 0 . O'A, ) 0 . O"-) 0. 0"-} I 0.0"-) I 0 .0%) '
3.2%)
I I I
FATIGUE/WEAKNESS I 0 0 0 I 0 I 0 I
'
3. 2"-) I 0.0"- J ( 0. O"-) 0 . 0"-) I 0,01,) I 0 . 0%) 3.2%)
I I I
INTEGUMENTARY SYSTEM 0 I 1 0 0 1 0 I 0 I
0.0%) I 3.2% ) 0.0%) 0.0%) I 0,0,. ) I 0 . 0%) 3.2%)
I I I
URTICARIA /H IVE S 0 I 0 0 I 0 I 0
0 . 0%) I '
3 . 2%) 0 . 0%) 0.0%} I 0,0,.) I 0 . 0%} '
3 . 2%)
I I
RESPIRATORY 0
0 . 0%)
I
I
0
0 . 0 %)
0
0 . 0%)
0
0.0"-)
I
I '
3 . 2,.)
II 0
0 . 07.)
1
3 . 2%)
UPPER RESPIRATORY INFECT., NOS 0

0 . Olio)
II D
O.Ollo )
0
0 . Olio)
0
0, O'A,)
I
I
I
1
3. 2')1.)
II 0
a.Olio)
1
3. 2%)
I
DI GEST I VE SYSTEM 0
0 . 0%) II 1
3.2% )
I
3. 2%)
O·
0.0%)
I
I
0
O.O'lo)
II 0
0.0%)
2
6 .5%)
I I
DIARRHEA 0 I 0 I 0 I 0 2
( O.Ollo) I ( 3 . 2llo ) ( 3.2%) ( 0. Olio) I ( o . 0,-.1 I ( 0 . 07.) 6 . 5%)
-----------------------------------
PERSONS WI TH COMPLAINTS
----------1----------
2 I 3
------ ----
l
1----------1----------1----------
I O f 1 I 0
----- -- --- ------ 5-- ---
6.51,) I ( 9. 7% ) 3. 2,i,) I ( 0.0%) I ( 3. 2,-.) I ( 0.0%) ( 16 . 1% )
0
0
O"'
-
~
Table 3 (cont)
PATIENT COUNT CLINI CAL COMPLAINT S
RECOMBINANT HEPATITIS B VACC INE
STUOV 0809
TREATMENT
DOSE 2 .5 MCG
PA TIENT CLASS: HEA LTHV CHILDREN
TOTAL VACCI NEE S ( 32 PAT IENTS ) - DO SE 2 I

----------------------- -------------------------
DAVS POST VACCINATI ON
------ --------------------~-II NUMBER
CLINICAL -----------------------------------------
I. I I
-------------------
I I
---------
I
------- 1I COMPWITH
........•......•................•.•
COMPLAINTS 0 1
········••1••······••1••···
2
···•• 1
3 4
••······••1••·······• 1
5
••·······•1••······•• 1
LA I NT S
••········
PERSONS WITH NO COMPLAI NTS
---------- 1----------1---------- 1---------- 1----------1----------1--- -------1-----------
29 I 2e I 30 I 31 I JO I 31 I I 26
< 93.s,r,) I < 90 . 3%) I c 96.8%) I (100.0~> I < 96.a,r,) I (100.0,r,J I I c 83 . 9,r,J
PERSONS WITH NO DATA ------~---1------~---1------~---1------~--- 1------~--- 1------~--- 1---------- 1--- ---~----

( :i.1,r,) I c 3 , 1,r, J I c ::i. 1,r, ) I< ::i. ,~> I c ::i . 1,r, J I c ::i . ,,r,J I I c :i . 1,r,J
0
0
0-
....
'"
Table 3 (cont)
PATIENT COUNT CLINICAL COMPLAI NTS
RECOMBINANT HEPATITIS 8 VACC INE
STUDY 0809
TREATMENT
DOSE 2.5 MCG
PATIENT CLASS : HEALTHY CHILDREN
I TOTAL VACCINEES ( 30 PATIENTS) - OO SE 3 I

l----------------------------------------------------------------------------1
I DAYS POST VACC INATI ON I NUMBER
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------
I O . I I I 2· I 3 I 4 I 5 I
1 WITH
!COMPLAINTS
··························· ······•• 1----
------------- ---------------------- 1••······••
--- --- 1••······••1••······••1••······••1••·······•1••······••
1----- 1••······••1••········
----- 1-- ------ - -1 ----- ----- 1---------- 1----------1- -------- - 1-----------
SVSTEMIC I I I O I I I I I O I O I I 2
I c 3.3%) I < 0.0%) I < 3 . 3%) I c 3 . 3~ l I C o.O% l I < o .o%l I I < 6.7~l
---------------------------------------------- ---------------------
I
---------- ---------- ---------------------------------
I
WHOLE BODY/GENERAL l o I 0 0 0 o I 1
3.3%1 o. o,o I 0 . 0%) 0. 0%) 0.0%) o .O"-l I 3 .J'lf.J
I I
o I o
HEADACHE 1
3.3%) o .o'JI.J I
I
0
0.0%)
0
0 . 0%)
0
0.0% ) a.a... , II I
3. 3'lf.)
RESPIRATORY l o I 0 0 0 o I I
3 . 3%) o.o'JI.) I 0.0%) U . O'lO 0 . 0 %) u. □%I I 3 .3%,)
I I
UPPER RESP! RA TORY INFECT., NOS 1
3 . 3%) D.~%) II 0
0. 0%. J
0
0 . 0%)
0
0. 0%) o_g""> II 1
3 . 3%)
DIGESTIVE SYSTEM 0 0 I l I 0 o I 1
0.0%) o.o"J I < 3.311. l 3 . 3%) 0 .0%) o.0'4l I 3.3%)
VOMITI NG 0
0 . O'Jl.l c
o
o. o%l I ,
I
I
3.311.l
I
3 . 3'l)
0
0 .0%)
0
c o .O'!I.J I
I I c 3 . 3<r.J
PERSONS WITH COMPLA INT S
---------- ----------,----------
l 0 I
----------
I 0
------0---,----------,------2----
3.3%) C o . o'!I.J I ( J . Jr. J 3 . 3'!t) 0 . 0% ) ( o .o"-> I I c s . 7'lf.J
PERSONS WITH NO COMPLAINTS

----------
29
----------1----------
Jo I 29
----------
29 30
-----;~---1----------1-----;~----
PERSONS WITH NO DA TA
c 96 . 7%)
o I
c100.0%l I ( 96 . 7%J
----------1 -- -------- 1----------1----------
O I O I
c 96 . 7'!1.l
0
( 100 . 0% )
0
-~~~~~~~~-1----------1-~-~~~~~~--
o I I o
o . O'Jl.l I c 0. 0%) I ( o.o'JI. J C o . O'!I.J 0 .0%) O.O'Y.l I I ( 0 . 0%)
Ta ble 4
RECOt'BINANT HEPATITIS B VACCitlE
STUDY 0809
TREATMENT
LOT t1Utt3ER CK444
DOSE S t1CG
PATUHT CLA!IS HEALTHY otILDREH
I TOTAL VACCIHEES ( 22 PATIEHTSI - DOSE l I

1I-------------------· --------------------------------------------------------1
DAYS POST VACCINATION I lfJHBER
CLINICAL
Cot1PUINTS
l----------------------------------------------------------------------------1
I G • 1 • t I 3 • 4 • S •
MITH
•c0t1PUINTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------l----------l----------l----------l----------l----------l----------
srsut11c I 1 I l I 2 I 3 I 3 I o I
l----------l-----------
I 3
f C 4 . 8 i0 I I 4.8X ) IC 9 . 5 XI IC 14 . J X) . C 14. 37. ) . C 0.07. ) . IC l't . J X I
I
NIOU BOOT/GENERAL I 0 0 U t l O Z
I o. ox1 o . o;o , 0.0:1.1 , 9.s:1.1 9. s:o t o.o;o 9.s:1. 1
I
FATIGUE/WEAKNESS I O O O 1 l 0 l
I C O. 07. I O. OX I C O. ox I 4 .ex I t 't. 87. I t O. 07. I t 4 . 8 Y. I
I
HEADACHE I O O O 1 l O l
I C 0 . 07. 1 I 0 . 0:I.I C 0 . 0:I.I C 4 . 8%1 C 4.87. I C O.OX I C ~ .8 XI
I
IHTEGU'1f:HTARY SYSTEM I 1 1 1 1 l 0 1
I 4 . 8iO 4 .81/.1 4' . 81/. l 4 .81/.1 4 . 87.1 0. 07. 1 4 .81. l
I
PAPUUR RASH I 0 0 0 l 1 0 1
I o.o:o o.or.1 o.ox1 4 .8 iO 4.87. 1 o.ox , 4 .e x ,
I
RASH, NOS I 1 l 1 0 0 O 1
I 4 . 8 1. I 4.87. 1 4.97. 1 0 . 07. t O. OXI 0 . 01. 1 4 . 8 7. 1
I
RESPIRATOl!Y I O O 1 1 0 0 l
It 0 . 01. 1 C 0.0:I. I 4 .8:I. I 4 .8 7.1 O.OXJ 0.01. J 4 . 8 Y. I
I
RHINITIS I O O 1 1 O O l
I t o . o;o I c 0.0:1. 1 c 4.e:1. 1 , 4 . e ;o , o. ox1 I c o.ox , I c 4.ex 1
-----------------------------------1----------I----------I----------
PERSONS WITH COUPLAIHTS I 1 I l I 2
----------1----------1----------1----------I-----------
3 I '3 I O I I 3
I c 4 . a x , I c 4.ex , I c 9.sx ·1 c 14 . l X I • c 14 . 3:1. I • c o . o;o I I c 14.3%1
-----------------------------------1----------I----------
PERSONS WITH HO COt1PUIHTS I 20 I 20
I----------
I 19
----------1----------•----------
18 I 18 I 21
l---------- I•----~------
I 18
· I I 95.ZXI . I 95 .2i0 I 1 90 . 57.1 I 85 . 77.1 It 85 .77. 1. 1100.0XI I I 1 85 .77.1
-----------------------------------t----------l----------1
PERSONS MITH HO DUA I l I l I
----------1
1 I
----------1
1 I
----------l----------l----------
l I l I
t-----------
I 1
I I 4 . 5 1. 1 I I 4.57.1 I I 4.57. 1 I ( 4 .5 7.1 I ( 4 . 5 7. 1 I ( 4 .51. 1 I I I 4 . 5 7. 1 0
0
0-
....,
~
·-
Table 4 (cont)
PATIENT COUHT CLINICAL Cot1PLAINT5
RECOttHtlANf HEPATITIS 8 VACCINE
SfUOT 0809
TREATMENT
LOT t-lllmER CK444
DOSE 5 t1CG
I TOrAl VACCINEES ( 2t PATIENTS! - DOSE 2 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I tM1BER
1----------------------------------------------------------------------------I
,
CLINICAL WITH
COl1PUINTS
I
t I 1
,
I
I I: I 3
,
I
I °'
................................... ,.......... .......... .......... .......... ,..........•.......... .......... ..........
I I 5
I
• ICOt1PUINT5
I I
,
I
,
I
REACTION, LOCAL llNJECT. SITE I I O I 1 I O I O I O I O I I 1
I c t . o;o I ( 5 .6iO I c 0. 0x1 I c o. 0x1 I c o.o:o I I o. o:o • I 1 5 .6½ 1
-----------------------------------1----------t----------l----------
ECCHYttOSIS · I O I 1 I O
t----------l----------l----------l----------
I o I O I o I l-----------
I 1
I c t.Oi: I I ( 5.67. 1 I c o . 07.l I c 0 . 07. 1 I 1 0 .ox 1 I I o . ox 1 I I 1 5.67. 1
-----------------------------------l----------l----------l----------l----------l----------•----------
sysnt11c I 2 I 2 I 1 I 2 I o I 1
l----------l-----------
I I 4
I I 11.17.1 I ( 11 .17. 1 • I 5.67.l I I 11 . 17.1 I ( O.OZ I I c 5 . 67. I I I c 22 . 27. 1
---------------------------------------------- ---------- ------------------------------------------- ----------------------
..iOLE llODT/GEHERAL 1 1 0 0 0 1 3
( 5 . 6 i: I 5 . 67. I ( 0 . 07. I ( 0 . 07. I ( O. 07. I ( 5.67. 1 ( 16. 77. I
FATIGUE/WEAKNESS 1 0 0 0 0 1 2
5 . 6 i0 O.OZ I O.OZ I 0 , 07.) 0.07. I 5 . 67. 1 11,17. 1
BRUISE FROlt VENIP\MCTURf 0 1 0 0 0 0 1

0 . 07. ) 5.67.) 0 . 07.) 0 . 07.) 0 . OZ I 0. oz I 5.6i0
RESPIRATORY 0 0 1 1 0 0 l
0 . 07. ) o.oz, 5 . 67.) 5 . 61. I o. oz ' o . oz ' 5 . 6 7. 1
PHARYHGITI$ CS~E lltROAT I 0 0 1 1 0 0 l

( 0 . 07. I I 0 . 01. I 5 . 6 7.1 S . 6 7. 1 ( 0 . 07.1 I o . oz ) I 5 .67. 1
DIGESTIVE SYSTEM 0 1 0 1 0 0 2
( 0 . 07. ) 5 .67. I 0 . 0¼ f 5 . 6%) o.o:o 0.0::! I ( 11 . 17. 1
TEETHING 0 1 0 0 0 0 l
( 0.07. 1 ( 5 . 6½ I ( 0 . 07. l 0 . 0½1 ( 0 - Q i( ) ( 0 . 0½) ( 5 .6½ )
I
DIARRHEA I 0 0 0 1 0 0 1
I ( O.Oi: I ( 0 . 07. I ( 0 . 07. l S . 67. 1 0 . oz I ( o . 07. I ( 5 .67. I
I
VOltITING I 0 0 0 1 0 0 1
I O.OZ I o.ox, O. OXl S . 6 i0 0 . oz I O. OZ 1 5 . 6 7. 1
0
0
0-
..._,
I.It
•
Table 4 ( cont)
RECOtl3111ANT HEPATITIS B VACCINE
STUOY I 0809
TREATMENT
LOT NUtl3Ell Cl<444
DOSE 5 MCG
PATIENT CLASS : HEALTHY CHILOREM
I TOTAL VACCINEES C Zt PATIENTS I - DO:IE Z I

l----------------------------------------------------------------------------1
I DAYS POST VACCUIATION I tu18ER
CLINICAL
C0f1PUINTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I 3 I 4 I 5 I
WJTH
ICOHPUIHTS
•••••*•••••••••••••••••••••••••••••I••••••••••
I
•••••••*••I•*•••••*••
I
••••••••••l•••••••••*l••••••••••l••••••••••I••••••••••
I I I I
PSYCHIATRIC/BEHAVIORAL I l l I O O I O I O I I Z
I I § . 6 %1 I 5 . 621 I I O. OX) l 0 . 0ZI I ( O. OZ I I ( O. OZ I I I l 11.lZI
I I I I I I
IRRITABILITY I l l I O O I O I O I I 2
I I S. 6% I I 5. 6X I I C O. OZ l C O. OZ I I C O. OX I I C O. OZ I I I I 11. l Z I
-----------------------------------1----------
PERSOHS WITH COl1PUJNTS I 2
----------1----------
3 I 1
----------1----------1----------1----------I-----------
2 I O I l I I 5
I I 11.lZI I l6 .7X I I I 5.6%1 I 11 . lZI I I O. OZI I C 5. 6ZI I IC 27.8XI
-----------------------------------1----------
PERSONs WITH HO COMPLAINTS I 16
----------1
15 I
----------
17
----------
16
l----------1----------1----------1
I 18 I 17 I I
-----------
13
I I 88. 9ZI I 83 . 3%1 IC 94.4%1 C 88 , 9%1 I (100.0XI IC 94.4XI I I I 72.2%1
-----------------------------------1----------I----------
PERSONS WITH HO DATA I 4 I 4
I----------
I 4
----------
4
l----------1
I 4 I
----------1
4 I
----------1I -----------
4
I I 18.2Xl I I 18.2%1 I I 18.2%) I 18,2% 1 I I 18.2XI I I 18.2Xl I If 18.2Xl
Table 4 (cont)
PATIENT COIMT CLINICAL COMPLAINTS
REC0t18INANT HEPHITIS 8 VACClNE
STUDY
TRUTI1ENT
LOT NI.Jt18ER CK444
DOSE 5 MCG
PATIENT CLAS~P HEALTHY CtlILDREH
I TOTAL VACCINEES C 2l PATIENTS I - DOSE 3 I

l----------------------------------------------------------------------------1
I DAYS POST VACCmATIOH I tuffllER
CLINICAL l----------------------------------------------------------------------------1 MITH
Cot1PLAIHTS I O I l I Z
-----------------------------------l----------l----------l----------
I 3
l----------
I 'I • 5 .
,
...................................•..........•..........•..........•.......... ,.......... ..........•..........•..........
.COMPLAINTS
l----------l----------l----------l-----------
srs1en1c • 1 • 1 • 1 • 1 I 1 I 1 I I 1
• I 5.0X> I I 5.0XI I I S . OXI • I 5.0%1 I I 5 . 0 7. 1 I t S . OX I I • ( S . OXI
I I I I I I
RESPIRATORY I 1 1 I 1 I 1 I 1 I l I l
I 5.01.) 5.01. I I C 5 . 0%1 I I 5 . 0%1 I I S . OY. I • I S . OY. I I C 5 . 0 %)
I I I I I I
UPPER RESPIRATORY INFECT. , HOS I 1 I l • 1 • 1 I 1 I 1 I 1
I C s . 01. 1 I c 5 . 0%1 I c s . 01.1 I c s.0%1 I I s.01. 1 I I s . 01. 1 I I c s . 0%1
-----------------------------------1----------I---------- I----------I----------I----------I---------- I----------I -----------
PERSONS WlTH CotfPLAIHTS I 1 I l I 1 I 1 I 1 I 1 I I 1
I c s.01.1 I < s.o;o • 1 s.01.1 I c s . 01.1 I t s . or. , • 1 s . o:o I I I s.ox,
-----------------------------------1----------1----------1----------
PERSOHS WlTH NO COMPLAINTS I 19 I 19 I 19
l----------l----------l----------l----------1-----------
I 19 I 19 I 19 I I 19
I ( 95 . 0%I I I 95. ox I I C 95 . o;o I C 95. 0%I I I 95 . 0%I I C 95 . o:o I I I 95 . 0% I
-----------------------------------•----------1----------1
PERSOHS WlTH NO DATA I 1 I l I
----------1
1 •
----------l----------•----------l----------
1 I 1 • I I
l--- ·-------
• 1
I I 4.8%1 I I 4.81. 1 I I 4,81/.1 I I 4.81/. 1 I I 4 . 8%1 I I 4 . 81/. ) I I I 4 . 8%)
,,
Table 5
PATIENT COUNT NAXIt1Ul1 TENPERATURES
REC0118INAHT HEPATIJIS 8 VACCWE
STUDY 0609
lREATt1EHT
lOT NU1BER I CK7J2
DOSE 1.25 HCG
I TOTAL lfACCil-tEES I 26 PATIENTS I - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I NtmBER
n,x TEMPERATURE
lDEG F, ORALI
1---------------------------------------------------------------------------------------I
I 0 I 1 I 2 I l I 4 I 5 I I
WITH
I HA)( TEMP
•••••••••••••••••••••••• •••••••••• •••••••••• •••••••••• •••••••••• •••••••••• ••••••••••l••••••••••I•••••••••• ••••••••••
HMl1AL l l 2 z 2 t l
S.JlO S .liO 10 . 0 iO I 10 . 0lO I 10. 0 1/.1 ( 10 . 01/. 1 S. OZ I
< 99 u ll ll H 14 11 8
52 .6Y. I 68 . 4 Y. I 65 . 0 Y. I 60.~Y.I 70 . 0 1/.1 65. OY. I I 40 . OY. I
99 - 99 . 9 6 4 J s 4 4 7
31.6Y. I 21 . 1 ;0 15.01/. ) 25.01/. I 20.01/.1 20.0iO Js .o:o
100 - 100 . 9 •
0 . OY. I
0
0 . 0 %)
0
0 . 0 %)
l
S . 0%I
0
0 . 0%)
1
5.0%)
l
5. 0%J
101 - 101.9 t 0 l 0 0 0 l
10.s;o 0 . 0 %) 5.0%) 0.07. I 0 . 0%) 0.0% I 5 . 01/. I
1oz - l0Z,9
•
0 . OY. I I
0
0 . 0 1/.)
l
5.0Y. )
0
O.OY.I
0
O.OY.I (
0
0 . OY. I (
1
5 . 0)0
103 - 103.9 I 1 0 0 D D 1
I 0. OY. I I 5. 3%l I O. OiO l 0. 07. I I 0 , 0 1/. I I O, 07. I I 5. 01/. I
------------------------I----------I----------
TEt1PERATURE TAKEN I 19 I 19
I----------I----------
I 20 I 20
I----------I----------I---------------------
I 20 I 20 I
I-----------
I 20
I I 73. lY. I I C 73 .17.1 I C 76. 9 i0 I I 76. 9% I I C 76 . 9%) I C 76. 9i0 I I C 76. 9%I
------------------------1----------1----------1----------1----------1----------1
TE~PERATURE NOT TAKEN I 7 I 7 I 6 I o I 6 I
----------1---------------------1-----------
6 I I 6
I I 26.97.1 I c 26.9%1 I I 23.1%1 I I 23 .1%1 IC 23 . 17. I I c 23.1%1 I I I 23.li!I
0
0
O"
....
01
Ta ble 5 (cont)
PATIENT CO\JHT MAXIHUN TEMPERATURES
RECOHBINANT HEPATITIS 8 VACCINE
STUDY 0809
TREATMENT
LOT HUHBER CK732
DOSE 1 . 25 11C6
PATIENT CLASS: HEALTHl CHILDREN

1----------------------------------------
I
.----------------------------------------------1I HUt18EA
NA)( 1El1PEAATURE
(DEG F, ClRAL)
1---------------------------------------------------------------------------------------I
I t I 1 I 2 I 3 I it I 5 I I
WITH
I MAX TEMP
•••••••••••••••••••••••• •••••••••• •••••••••• •••••••••••••••••••• •••••••••• •••••••••• ········••1••········ ••••••••••
NORMAL 1 l 1 1 1 1 l
S.6%1 5.1>% I 5 . 9%) ( 5.6Y. I ( 5 . 9%) ( 6 .3%1 5 . 1>%)
< 99 9 10 9 7 9 9 6
5t.0%1 55 . 6%1 52,9%1 38 . ,r. I 52 . 9% I 56 . 3%1 I 33 . 5%1
99 - 99.9 e 7 6 9 6 6 9
"" .4)0 38. 97.1 35 . l iO 50, OZ I 35. 3;0 J7 . 57.1 50.0iO
100 - 100.9 0 0 1 0 1 0 l
o.o;o 0 . 07. I S , 97.1 o.or. 1 5.9iO 0 . 0%1 5 . 6%1
101 - 101.9 0 0 0 l O O l
I O. 0% I I I O. o;o I O. 0%I I 5 . 6r. I I O. 0%I I O. 0%I I I 5 . 6%I
------------------------1----------1----------
TEHPERAT'-"E TAKEN I 18 I 18
----------1----------1----------1----------1---------------------1-----------
17 I 10 I 17 I 16 I I 10
I I 69 . 27.1 I I 69 .2% 1 C 65 .47.1 I I 69.2XI I I 65 .47. 1 I I 61.5%1 I I I 69.vn
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEMPERAlUlE HOT TAKEH I 8 I 8 I 9 I 6 I 9 I 10 I I 8
I 1 30 . ex• I 1 30 . 8% 1 I c 3.4 . 6%, I , 30 . er. , I c 34 . 6%, I c 38 .sx I I I c 30. sr. 1
Table 5 (cone )
PATIENT CCMMT "AXIHUH TEHPERATURES
RECOt1BINAHT HEPATITIS B VACCINE
STUOY I 0809
TREATMENT
LOT HU18£R CK7l2
DOSE 1 . 25 ttCG
PATlEHT CUSS : HEALTHY CltllDREN

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I tlUHBER
1---------------------------------------------------------------------------------------I
MAX TEMPERATURE
IDEC F, OOALI It I 1 I 2 I 3
•••••••••• •••••••••• ........... ••••••••••
I" Is I I
........... WITH
I HAX TEHP
•••••••••• ••••••••••I••••••••••••••••••••
NORMAL
I
0
1 . 0:n
•
0 . 8% I
1
7 . 1%1 (
0
0 . 0%1
0
O. OY. I
0
0 .0% I I
0
O. Ol! I
< 99 10 1t e 9 10 11 (,
71.4iO 71.liiO S7,1%) 64 . 37.1 71.4iO 78.67.1 4~. 9)0
99 - 99 . 9 4
I 28.6iO "
28.67.1
4
28 . 67.1
5
35.7XI
4
28.67. I
3
21.47.1
7
50.0iO
102 - 102. 9 0 I 1 0 0 0 l
I o.o:n ( 0.17.I I 7 . 17.1 I 0 . 0iO I (1.07.1 I 0.07.1 I 7 . 17. 1
------------------------1----------1----------
TEHPERAT\JRE TAKEH I 14 I 14
----------1----------1----------1----------
14 I 14 I 14 I 14
---------------------1-----------
I 14
I I 56 . 0iO I < SC..07.I I 56.07. 1 I I 56 . 07.1 I c 56.0iO I I SC. . 07.1 I C S6.o;o
------------------------1----------1----------1----------1----------1----------1----------1---------------------1-----------
UHPEAATURE NOT TAKEN I 11 I 11 I 11 I 11 I 11 I 11 I I 11
I ( 44.0XI I I 44 . 07.) I I 44.07.) I I 44 . 07.1 IC 44.0XI I I 44.07.1 I I I 44. 07. I
0
0
(l-
oo
0
-
Table 6
PATIENT COU NT MAXIMUM TEMPERATURES
RECOMBI NANT HEPATITI S 8 VACC INE
STUDY 0 809
TREATMENT
DOS E 2.5 MCG
PA TIENT CLASS: HEALTHY CHILDR EN
I TOTAL VACCI NEE S ( 32 PATI ENTS) - DOSE 1 I

,---------------- ------------------------------------------------------
I DAYS POS T VACC INAT I ON
----- ------- -----1I NUMBER
MAX TEMPERATURE
( DEG F , ORA L)
1----------
I O
--------------------------------
I Z I 3
----------
4
--------------------------------
5 I I
WITH
MA X TEMP
•••• • • • ••••••• ••••• • • • ••I •••• • ••• • • •• • • ••• •• • 1• ••• •• • • •• 1• ••••• • •• • •••••• • ••• •• •••• • ••• f •• • •• • • • •• I••••• • • •• • •• • ••••• • •
NORMAL I 3 3 I 3 I 3 3 3 I 3
< 99 I 10 ::") ' \ :" ) I 10;:"' ) 1\ :" ) 10::"' ) 10;:"' ) ! 10

4 6. 7% ) es.O"K l I 53. 3%) 66.7%) 58 . 6%) 60 . 0% ) I 33. 3%)
99 - 99 . 9 ,1
36.7%)
s
11.2% )
II a
26 . 7%)
s
1s . 1%>
7
24 . 1% )
,
2J.3%J
II 13
43.3%1
100 - 100 . 9 0
o . 0%)
0
o .O"Kl
lI 1
3.3%)
2
6.7%)
I
3 . 4'111
2
s . 7% l
II 1
3 . 3%1
I I
10 1 - 10 1 . 9 2 I 2 0 I O I I 3
6.7%) c 3. 4% l I < 6.7%) o.O%l 3. 4% J < o.O%l I I < , o.o% l
------------------------ ----------
TEMPERATURE TAKEN 30
----------
29
1I ----------
30
----------
30
----------
29
----------1-
30 I
-------------------- I,-----------
30
( 93 . 8% ) c 90.6"Kl I < 93.6"K l c 9 3 .B" l < 9 0 . 6%) I < 9 3 .8%) I I c 9 3 .8%1
--- --------------------- ----- -----
TEMPERATURE NOT TAKEN 2
----------
3
1I ----------
2
----------
2
----------1----------1---------------------
3 1 z I
1I ----------·
2
6 . 3 %) 9. 4% ) I c 6.3%) 6.3"> 9 . 4"K l c 6.3%) I I < s.3"Kl
0
0
~
-
()>
Table 6 (cont)
PATIENT COUN T MAXIMUM TEMPERATURES
STUDY 0809
TREATMENT
DOSE 2 . 5 MCG
DAVS POST VACCINATION NUMBER

MAX TEMPERATURE WITH
(OEG F , ORAL) 0 I I I 2 I 3 4 I s I MAX TEMP
••••••••••••••••••• ••• •• •••••••• • • l •••••••••• t• • •• •••••• I••• • •• ••• •
I I ········•• 1I ••···· ···· ········• •1 ••········ ••••••••••
NORMA L 5 s I s I 5 5 5 5
20.01,) 20 . e-,.J I 20 . e-,.J I 20.0%) 20.8%) 20 . 8%) 19. 2% )
I I
< 99 10 10 I 13 I 14 14 13 13
40 . 01,) 41 . 7%) I 54. 2%) I 56.0%) 58.3%) 54.2%) 30 . 8% )
I I
a I I s
99 - 99.9 7
28.0,.) 33.3%) I 25.0%)
6
I 24.0%) 16.7%)
4
20.8%)
5
I
10
38 .5%)
100 - 100.9 3 I I O I 0 I I 3
TEMPERATURE TAKEN
---~~:~~~- -~--~:~~~-1-~--~:~~~-1-~--~:~~~-
25 I I
24 24 2s
4 .2'1.)
---------- ---------- 1I ---------- -----------
24
c 4 .2%)
24
I 11 .5% )
26
( 78 . 1,r.) < 75 . 0%) I < 1s . o'I.) I C 78 . 1%) < 75 . 0'l.l < 75.0%1 I ( 81 . 3% )
TEMPERATURE NOT TAKEN

----------
7
-- --------
8
1----------1
I e I
---------
1
- ----------
8
----------1
e I
----------- ---------- 6
( 2 1. 9%) c 2s.O%l I C 25.0'J.l I C 21.9%) < 2s.O%l < 2s.0%J I ( 18.8% )
0
0
a-
a,
rv
Table 6 (cont)
PATIENT COUNT MAXI MUM fEMPERATURES
STUOV , 0800
TREATMENT
DOSE : 2.5 MCG
TOTAL VACCJNEES ( 30 PATIENTS) - DOSE 3
OAVS POST VAC CINATION NUMBER

MAX TEMPERATURE WITH
(DEG f, ORAL) o I 1 · I 2 I 3 I 4 s I I MAX TEMP
•••••••••••••••••••••••• •••••••••• i ••••••••••l••••••••••J••••••••••t•••••••••• ••••••••••l••••••••••I•••••••••• ••••••••••
I I I I I
NORMAL s I s I 6 I s I s s I 5
19.2,r,J I 19.2,r,) I 23.1"> I 19 .2,r, J I 19.2~> 19 . 2%) I 19.2%)
I I I I I
< 99 9 I 14 I 13 I 13 I 16 16 I 4
34.6%) I 53.8"') I 50.0"l I so.o% J I 61.s,r,) 61 . 5%) I 15.4%)
99 - 99.9 II
I
I
4-1 . 3%) I
7
26 . 9,r,)
II 6
23 , 1")
I
I
I
7
26 . 9%)
I
I
I
4
is . 4,r,)
5
19 _;1,.)
I
I
I
14
53.8% )
I I I I I
100 - 100. 9 I I o I I I o I 3
I < 3.8,r,J I < o.o,r,J I c 3 . 8"> I c 3.a,r, J I < 3.8%> c o . o,r,> I I < 11.s,r,J
------------------------1----------1
TEMPERATURE TAKEN I 26 I
----------
26
1----------
I 26
1----------
I 26
1I ----------
26 ·
----------1-
26 I
--------------------1-----------
I 26
I c 86 . 7"') I c 0s .1,r,) I c 86 . 7"> I c 86.7% ) I c as .1,r,1 ! 86 . 7"') I I < 86.7%)
------------------------1----------
TEMPERATURE NOT TAK EN I 4
1----------1----------1----------1----------
I 4 I 4 I 4 I 4
----------1---------------------1-----------
I I 4 4
I c 13,3,r,J I < 13 . 3%) I < 13 .3") I c 13 . 3%) I < 13 , 3,r,J < 13 _3,.J I I < 13 ,3,r, J
Table 7
PATIENT COUNT HAXI~ TEl1PERA~ES
RECOl18INAHT HEPATITIS 8 VACCINE
STUDY I 0809
TRUTNEHT
LOT IU18EA CK444
DOSE 5 t1C6
PATIENT CUSS: HEALTHY CMILDREN
I TOTAL VACCIHEES C 2Z PATIEHTSI - DOSE 1 I

1---------------------------------------------------------------------------------------I
I DArs POST YACCIHATIOH I HUNBER
~AX TEl1PERATURE
(DEG r, MAU
l----------------------•----------------------------------------------------------------1
I O I l I 2 I l I 4 I S I I
MITH
I HA)( TEl1P
•••••••••••••••••••••••• •••••••••• •••••••••• •••••••••• •••••••••• •••••••••• •••••••••• ••••••••••l••••••••••I••••••••••
HORNAL 1 l l l l l l
tt.a:o S.OZl 4 . 8Z I s.o:o 5. oz I 5 . oz I 4 . 87. 1
< '19 9 11 11 11 12 10 5
42. 97.1 55 . 0Zl S2 , 4Z I 55,07.) ( 60.0:0 50 . 07. I 23.87.1
99 - 99. 9 a 7 7 8 6 8 11
le,17. ) 35 . 07.) 33. 37. ) 40,07. ) 30 . 07. I 40,07.1 52.4i0
100 • 100. 9 l 1 2 0 1 l 4
I 14 . J iO C S . OZl C 9 , SXI C O.o:o C 5 . 0)0 C S.o;o I 19. 07. I
------------------------1
TEt1PERATUA£ TAKEN I
----------1----------
21 I 20
I----------
I Z1
I----------I----------
I 20 I 20
----------
20
I--------------------- II-----------
I 21
I I 95. s:o I C 90 . 97.) I C 9S. sx I I C 90, 97. I I l 90. 97. I C 90. 97. I I I C 95 . 57. I
------------------------1----------1----------1----------1----------1----------1----------1---------------------1-----------
TEHPEIIAT~( t«>T TAKEN I 1 I 2 I l I 2 I 2 I 2 I I l
I I 4.57.1 I C 9.lXl I l 4.SXI I C 9.17.1 I l 9.17.1 I I 9.liO I I I 4.57. 1
-
Table 7 (cont)
PATlEHT COUNT nAXll'1U'1 TEnPERAl~ES
RECot1BlllANT HEP ATITIS 8 VACCINE
STUDY 0809
TRUTl1fNT
LOT .utl!ER CK444
DOSE 5 tlCG
PATIENT CUSS: HEALTHY CHILDREN
I TOTAL VACCINEES I 22 PlTIENtS l - DOSE 2 I

1---------------------------------------------------------------------------------------I
I OATS POST VACCIHATIOH I NU'IBER
HlX TEHPERATURE
I DEG F, (IIULI
1----------------------------------------
Io I 1 I 2 I 3 •----------------------------------------------I
I 4 Is I I
WITH
I HAX TEHP
••••••••••••••••••••••••••••••••••I••••••••••••••••••••••••••••••••••••••••••••••••••
I
••••••••••I••••••••••••••••••••
NORHll 3 I 3 3 3 3 ]
1a.a;o I ie.a:o 18.8:I. ) 18.8Y. ) 21.ltXI 18.8i0
I
< 99 7 I o 0 9 9 0 5
43 . 8:1.1 I so . Ol l S3. 3:1. ) S6 . J:I. I S6 . 3 l l S7. lY. I I . 31. 3:1. I
I
99 - 99.9 s I 4 ] 3 3 ]
31 , 3:1. 1 I 25,0,n 20.0;0 18 , 8%'. l 10. 8 i0 21.4:1.1
I
100 - 100.9 o I 0 l l l 0 0
0 . 0:1.1 I 0. OY. I 6.7:1.) 6 . 3:1. l 6. Ji! ) 0.OX I 0.0:1. I
I
101 - 101.9 l I l O O O O l
I 6 . 3;0 I I 6. 3i0 I O. o;o I O. OY. I ( 0. OiO I O. 01.1 I 6. 31. I
------------------------l----------l----------l----------l----------l----------1----------1---------------------l-----------
n:nPuATURE TAKEN I 16 I 16 I u I 16 I 16 I 14 I I 16
I f 72 . 7Y.) I f 72 . 7l I I ( 68 . 2:0 I I 72 . 7;'.) I f 72 . n, I I 63 . 6%'. I I I I 72. 7:1.)
------------------------I----------I----------I----------I ---------- I----------I----------I ---------------------I-----------
T£11PERAT\JlE HOT TAKEN I 6 I 6 I 7 I 6 I 6 I a I I 6
I I t7.3XI I I 27.3XI I I 31.0XI I I 27,3XI I I 27.3ll I I 36.4XI I I I 27.3XI
0
0
0-
c»
~
Table 7 (cont)
PATIENT Cou-fT NAXIHUH TEHPERAT\JRES
STUDY 0809
TREATHEHT
LOT tu18ER 1 CK444
DOSE S t1CG
PATIEHT CLASS : HEALTHY CttILDREH
I TOTAL VACCIHEES I Zl PATIEHTSJ - 0OSE 3 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I . HUM8ER
NAX TEHPERAT\JRE
(OfG I', ORALJ
l---•-----------------------------------------------------------------------------------1
I O I l I Z I 3 I 4 I 5 I I
WITH
I HAX TEHP
•••••••••••••••••••••••• •••••••••• •••••••••• •••••••••• •••••••••• ••••••••••••••••••••••••••••••I••••••••••••••••••••
4 4 4 4
HORHAL
"
22.2Y.I
4
22.2:0 ( tt.ZY.I ( 22.z:o C 22.ZY. I C 22 . 2:0 "
22 . 2%I
< 99 11 11 11 2
"
22 .ZY. I
9
50. 0 1. J 61. l Y. J
10
55.6%) 61 . 1%) 61 . u : I 11.1% 1
99 - 99.9 e 4 3 4 l l 10
44.4:1.1 22.27. 1 1'>. 7%1 22 . 2;0 16.7%1 16. 71. 1 55.67. 1
100 - 100. 9 1 1 0 0 0 0 1
5 . 6:1.1 5 . 67.1 O. OY.I 0 . 0%1 0 . 0:1.I I 0.01. 1 5.61. 1
I
101 - 101. 9 1 o o o o I o 1
1 5 . 6:1.1 « o . oz 1 , o.o;o I , 0 . 01. 1 t 0 . 01. 1 I , o.o;n • 5 . 6 1. I
------------------------1----------1----------1----------1----------1----------1----------1---------------------1--
TEl1PERATURE TAKEN I 18 I 18 I 18 I 18 I 18 I 18 I I
·--------
18
I I 85.7:1.1 I« 85.7i!I I I es.71.1 I« 85 . 7:1.I I ( 85 . 71. 1 IC &5. 7i0 I I I 85.71. 1
------------------------l----------l----------l----------l----------l----------l----------l---------------------l-----------
rEt1PERATURE HOT TAKEN I 3 I 3 I 3 I 3 I l I 3 I I 3
I 1 14. 3%> I c 14.37. 1 I 1 14.3% 1 I c 14.3%1 I c 14. 3%1 I c 14 . 37. > I I 1 14.31/.I
....
(/)
c::
c:,
-<
CX)
°'
en
00687
PURPOSE: To evaluate antibody and clinical responses to two or

three 5 mcg doses of vaccine among healthy infants and
children, ages 3 months through 11 years, who are
seronegat1ve for hepatitis B markers.

Lot# 985/C-K732 (5 mcg/ml )
PRIHAKY Prof. E. K. Yeoh, M.D.

INVESTIGATOR : Consultant Physician
Medical A Unit
Queen Elizabeth Hospital
Wylie Road
Kow1oon, Hong Kong
SECOHDARY W. K. Chang, M. P., B.S., F.R.C. Path.
INVESTIGATOR: Consultant Microbiologist
Queen Mary Hospital
Pokfulam Road
Hong Kong
Ching Lung Lai, M.B., M. R. C.P . . F. R. C. P.
Queen Mary Hospital
Pokfulam Road
Hong Kong
STUDY LOCATION: Queen Elizabeth Hospital

Wyl ie Road
Kowloon, Hong Kong
Queen Mary Hospital
Pokfulam Road
Hong Kong
DATE INITIATED: 2/1/85
STUDY POPULATION: The study population will consist of 100- 200 infants
and chi l dren, ages 3 months through 11 years, who are
negat i ve fo r hepatitis B serolog1c markers and have
not previously received any hepatitis B vaccine .
23921/00851/1
1/18/86
00688
Study 865
PROCEDURE: Participants are randomly assigned to one of 2 groups

with 50-100 ch i ldren or i nfants in each group. Group
one receives intramuscular injections of vacc i ne at 0
and 1 month (5 mcg doses) . Participants in group 2
rece i ve their injections at 0, 1 and 6 months . The
parent or guardian is asked to record the child s I
temperature for 5 days after each injection and note

any local or systemic complaints .
Blood samples are obtained prior to vaccination and at
l, 3, 6, 8, 12 and 24 months post initial injection.
All samp les are assayed for HBsAg, anti-HBs, anti-HBc
and ALT by Or. Yeoh. Some samples may be tested for
yeast antibody at MSDRL. Samples with an anti-HBs
ti Ler > 25 mIU/ml may be tested to determine anti-a
and anti-!!. activity. -
RESULTS: HEALTHY INFANTS ANO CHILDREN:

5 mcg Lot #985/C-K732 at O and l month
5 mcg Lot #985/C-K732 at 0, l, and 6 months
1. Number Vaccinated :
Injection No.
Grou(! I. Dose level _ l_ 2 _3_
l 5 mcg 90 70
2 5 mcg 88 12 46
2. ~erologic Results :
Sero logic data at 6 months are available for 24
participants in the two injection regimen. At
that time 98% (49/50) of the children
seroconverted (S/N ~2.1) for ant1-HBs and 94%
(47/50) developed protective levels of antibody
(mIU/ml ::_10). Among the 21 participants for whom
8 month serologic data are available in the three
injecl ion regimen, 100% (21/21) seroconverted and
developed protective levels of antibody (mIU/ml
~10).
A large boost in titer was seen among those

children who received the third injection.
Geometric mean titers at 8 months were 1894.8
23921/2
1/18/86
Study 865
RESULTS (CONT.) mIU/ml and 84.50 mIU/ml for those in the three and
t wo i njection groups, respectively. Tabl e 1 lists
seroconversion rates and GMTs for one to three
months of follow-up.
Clinical follow-up data are available for 142, 117
and 25 participants following injections one. two
and three. respectively.
T:,pe of ca.plaint Frequency in\ by Injection
2 (3/141 ) 2 (2/116) 0 (0/25)
Systanic {> (B/141 ) 4 (5/116) 4 {1/ZS)
There have been no serious or a lam i ng adverse

experiences attributable to the vaccine.
23921/3
1/18/86
Table I
Alltibody Responses ~ Healthy Children and Infants following Vaccination vith

5 11eg Injections of Yeast Rec<Jllbinant Hepatitis B Vaccine
lot 1985/C- K732 at 0, I, and 6 bths or 0 and l fl':>nth in Study 865
Gl"CX4) 1 Group 2
0 and I fl':>nth o- 1 and 6 bths
GIIJ '•IU/1111 '11T (IIIIU/nll
Time \ vith Anti..ffls All , vith Anti-415s All
Olonths) S/N ~ 2.I 111IU/111 ~ 10 Yaccinees Sf:N ~ 2.1 1111U/11I ?'., 10 S/N?'.,2. 1 11IlVinl ?'., 10 Vaccinees SIN ~ 2 . 1 mlU/ml ~ 10
l 33(23/70) 11(8/10) 0.8 8 .6 21.9 40(29/12) 15( 11/72) I. 1 9.1 29. 1
3 91(57/59) 83(49/59) 52.9 63.5 93. J 91(53/58) 19(46/58) 31.1 63 . -1 88.6
6 98(49/50) 94(-11/50 81.6 91.5 102. 5 98(45/46) 76(35/46) -12. 1 58.9 93.7
8 96(23/24) 88(21/24) 84.5 107 .9 14". 9 100(21/21) 100(21/21) 1894.8 1894.8 189-1.8
23921/3
l/18/86
0
0
0--
<>
0
PROGRAM: Alum-Adsorbed Yeast Reco111b'\nant Hepatitis 8 Vaccine,
Study 891
PURPOSE: To compare the antibody and clinical responses to

recombinant hepatitis B vaccine and plasma-derived
hepatitis· B vaccine among healthy adults and children
markers.
VACCINES: 1. Yeast Recombinant Hepatitis B Vaccine

Lot 979/C-KS64 {10 mcg HBsAg/ml}
Lot 0027L (20 mcg HBsAg/ml)
PRIMARY Dr. Hu Zong-Han

INVESTIGATOR: Department of B1ologica1 Products Inspection
Bureau of Pharmaceutical and B1olog1cal Inspection
M1n1stry of Health
SECONDARY .Dr. Shi Gu1yong

INVESTIGATOR: Director of Epidemic Department
STUDY .LOCATION: Shen Yang Municipal Anti-Epidemic Station

STUDY POPULATION: The study population consists of 200 healthy adults

and 200 healthy children of either sex (exlud1ng
and HBs, have a normal ALT level and have not
32121/1
1/17/86
Study 891
STUDY PROCEDURE: Participants are grouped by age and randomly assigned to

receive the yeast recombinant or plasma-derived
hepatitis 8 vaccine as follows:
Popul&tion Ve1ccine l)oSQ ~ illltfl
Adults Recald>inant 10 .u:g 50 1.0 1111 lntr1111.1scular

(?;30 years) injection of vaccine
at o. 1, and 6 months
2 Adults 10 mcg 50 1. o 1111 intr-..scular

( 18-29 yHrS) inject ion of vaccinel
n o, 1. and 6 month 1
3 Children 5 nicg 100 0.5 ■1 intrn,scular
(S-10 yHrs) injection · of vaccl
at o. 1, and 6 months
4 Adulb PlaSN 20 IIC9 so 1.0 111 intr-..scular

(?:30 yHrs) injection of v.icci
at O, 1• and 6 mnths
5 Adults 20 IIICg so 1.0 •1 intrn,scular

( 18-29 yHrs) injection of vaccfoe
at 0, 1, and 6 1110nths
6 Children 10 .cg 100 ~ intr1111.1scu1.,-

(5-10 yurs) injection of vaccine
at 0, 1, Ud 6 lll)llths
Study participants or the part1c1pant I s parent or

guardian record their temperature or that of their
child, and any local or systemic complaints for five
A blood sample 1s obtained from each study participant
approximetely two to three weeks before the first
injection of vaccine. Post-vaccination blood samples
are obtained at 1, 3, 6, 7, 8, 9, 12, and 24 months.
All serum samples are assayed for HBsAg, ant1-H8c,
ant1-HBs, and ALT.
32121/2
1/17/86
00693
Study 891
RESULTS: (Contd) To date 100 adults and children have received one
injection of yeast recOllbinant or plas111a-derived
hepatitis B vaccine. No serious or alann1ng reactions
Clinical follow-up data and serolog1c results are not
32121/3
1 /17/86
00b94
SUMMARY - DIALYSIS ANO PREOIALYSIS PATIENTS
To date, 288 patients with chronic renal insuffidency, including 210

patients who are receiving dialysis treatments (dialysis patients) and 78
patients w~o are not yet receiving such treatments (predialys1s patients),
have received one or more injections of the yeast recombinant vaccine.
Predialysis patients receive an injection of the yeast recombinant

hepatitis B vaccine (10, 20, or 40 mcg dose) at 0, 1, and 6 months. Dialysis
patients receive an injection of the vaccine (20, 40, or 100 mcg dose) either
at 0, 1, and 6 months or according to a more intensified regimen (20 or 40 mc9
dose) at 0, 1, 2, 3, 4 and 5 months. In four of the studies, patients
received the vaccine as an intrarauscular injection in the deltoid. However,
in one study (Study 838), vaccine was adrainistered in the buttock.
Post-vaccination clinical data are available on 135 dialysis and 49

predialysis patients following the third injection of vaccine, and for 33
dialysis patients following a sixth injection. Serologic data following the
last injection of vaccine are available for 50 pred1alysis patients and 84
dialysis patients who received three injections of vaccine and 32 dialysis
patients on the six injection regi11en.
IMMUNOGENICITY
Deltoid Injection: At 7-8 months 15% (10 mcg dose), 68% (20 mcg dose) and 67%
(40 mcg dose) of predialysis patients who received three injections of vaccine
in the deltoid had an ant i-HBs t 1ter of S/N >2. 1 . Protective 1eve ls of
antibody (S/N or mIU/ml ~10) were induced in 15%-(10 mcg dose), 58% (20 mcg
dose), and 61% (40 111cg dose) of vaccine recipients. Among patients with a
mini11um titer of S/N ~2.1, and for whom titers are currently available in
units of mIU/ml, the geometric niean titers were 67.7 111IU/ml (10 mcg dose),
213.7 mlU/ml (20 mcg dose), and 120.9 mIU/ml (40 mcg dose) at this time. For
responders with titers of at least 10 mIU/111, the geometric mean titers were
67.1 mIU/111 (10 mcg dose), 120.9 mlU/ml (20 1119 dose) and 186.4 mIU/ml (40 mcg
dose). By 12 months titers had declined with 0% (10 mcg dose), 50% (20 mcg
dose), and 40% (40 mcg dose) still retaining titers of S/N or mlU/ml >10
(Table 1). -
Buttock Injection: One month after the first injection of vaccine, 13% of
pred1alys1s patients receiving a 10 mcg dose in the buttock have detectable
antibody (S/N ~2 .1) with a geometric mean titer a1110ng responders of 4.6
mIU/ml. None had achieved a titer of mlU/ml ~10 (Table 1).
Dialysis Patients
Deltoid Injection: At 7/8 months, among dialysis patients who had completed
the standard three injection regimen in the deltoid, 59% (20 mcg dose) and 94%
31431/1
00695
(40 mcg dose) had an anti-HBs titer of S/N ~2.1, while 48% (20 mcg dose) and
88% (40 mcg dose) achieved protective levels of antibody (mlU/ml ?,10). The
geometric mean titers at 7-8 months for patients with anti-HBs 2:,2 .1 S/N was
69.1 mIU/ml {20 mcg dose) and 331.8 mIU/ml (40 mcg dose), while for responders
with a titer of mlU/ml ~10 the GMTs were 118.6 mIU/ml (20 mcg dose) and 445.5
mIU/ml (40 mcg dose) (Table 2). Forty mcg doses of vaccine produced
significantly higher seroconversion rates {S/N ~2.1 and mIU/ml ~10) and levels
of response {GMT of all vaccinees) at 3, 6, and 7-8 months (See Appendix 1 for
statistical methods). By 12 months antibody levels had declined with 41% (20
mcg dose) and 71% (40 mcg dose) still retaining titers of mIU/ml >10.
Geometric mean titers of responders with protective levels of antibody
decreased to 79.9 mlU/ml (20 m~g ~ose) and 165.6 mlU/ml (40 mcg dose).
At 3 months (2 months after the second injection) 68% of dialysis
patients receiving 100 mcg doses of vaccine in the deltoid seroconverted (S/N
~2.1), with 25% developing protective levels of antibody (mIU/ml ~10). The
GMT of responders with antibody levels of S/N ~2.1 was 8.4 mIU/ml at this
time, while among responders with titers of mIU/ml ~10 the GMT was 33.3 mIU/ml
(Table 2). This study is still in progress and serolog1c results are not yet
available after the third dose of vaccine.
Buttock Injection: At 7-8 months 64% of dialysis patients who received 40 mcg
doses of vaccine in the buttock at 0, 1, and 6 months had an anti-HBs titer of
S/N ~2.1, while 58% achieved a protective titer of mIU/ml ~10. By 10 months,
65% still retained titers of S/H ~2.1, although the proportion with titers of
mlU/ml ~10 had declined slightly to 54%. At 7/8 months the geometric mean
titers of responders with titers of S/N ~2.1 was 90.2 mIU/ml, while responders
with titers of mIU/ml ~10 had a GMT of 115.5 mIU/ml. The GMT of responders
with protective levels of antibody remained fairly constant through 10 months
(Table J).
Among dialysis patients administered vaccine in the buttock at 0, 1, 2,
3, 4, and 5 months, 56% (20 mcg dose) and &9% (40 mcg dose) seroconverted {S/H
>2.1) at 6 months, with 44% (20 mcg dose) and 69% (40 mcg dose) ach1ev1ng a
.protective titer of mIU/ml 2:,10 (Table 3). There were no significant
differences found in these seroconversion rates by dose level at either
cutoff. At 10 months, 50% (20 mcg dose) and 67% (40 mcg dose) retained an
anti-HBs titer of S/N ~2.1, while 44% (20 mcg dose} and 50% still retained
titers of mlU/ml ~10. Responders with S/H ~2.1 had a geometric mean titer of
87.3 mIU/ml (20 mcg dose) and 189.8 mlU/ml (40 mcg dose) at 6 months.
Responders with mIU/ml ~10 had GMTs of 190 mlU/ml for both the 20 and 40 mcg
doses at this time. Through six months, levels of response (all vaccinees)
were not shown to increase significantly with log dose level. By 10 months
the geometric mean titers among patients with protective levels of antibody
declined to 55 mIU/ml (20 mcg) and 27.7 mIU/ml (40 mcg).
When seroconversion rates and titers among dialysis patients who received
three 40 mcg doses of vaccine in the buttock are compared to those who
received six 40 mcg doses of vaccine in the buttock, the two regimens were not
shown to be significantly different one month after the last injection of
vaccine. (The statistical analysis included two subjects with 9 month data
instead of 7/8 month data in add1t1on to those subjects su11111ar1zed above at
7/8 months).
31431/2
00696
SAFETY
The vaccine has been very well tolerated in predialysis and dialysis
patients. No serious reactions attributable to vaccination have been
reported. Most importantly none has occurred to ·date among individuals who
have received at least two 100 mcg doses or as many as six 40 mcg doses of
vaccine.
Among predialysis patients, mild transient injection site reactions and
systemic complaints were reported following injection of vaccine at
frequencies of 6% and 8%, respectively (Table 4). The frequency of coqplaints
after the first injection was higher than after the second or th1rd
injections. The 110st frequent injection site reaction was soreness (6%)
(Table 7). The most frequent specific systemic complaints were nausea (3%),
symptoms of upper respiratory infection (2%), chills (1%), and headache (1%)
(Table 8). A temperature ~100°F oral was reported following 8% of all
injections (Table 4).
Dialysis Patients
The incidences of local (injection site) complaints, of systemic
complaints, of e1ther local or systemic complaints, and of fever (oral
temperature of 10o•F or more) were analyzed statistically to evaluate the
safety of the vaccine in dialysis patients (See Appendix 1 for statistical
methods). The incidence at each injection was defined as the number of
subjects with the complaint at any time during the five-day period following
vaccination divided by the number reporting. while the total was the sum of
complaints following the three or six injections divided by the number of
injections with follow-up.
Mild transient injection site reactions and systemic complaints were

reported in dialysis patients following injection of vaccine at frequencies of
3~ and 7%, respectively (Tables 5, &).
Among those dialysis patients who received three injections of 20, 40, or
100 mcg administered in the deltoid or the buttock (Studies 816, 825, 838),
loca 1 complaints increased significantly with log dose level at the second
injection while systemic complaints decreased with dose level at the first
injection. The most frequent injection site reaction was soreness (3%)
(Tables 9, 11), and the most conrnon systemic complaint was fatigue (2%)
(Tables 10, 11). A temperature of ~100°F (oral) was reported following 4% of
all injections (Table 5). The rate of complaints appeared to be highest after
the first injection and lowest after the second injection.
Among dialysis patients who received six injections of 20 or 40 111cg of
vaccine administered in the buttock, complaints were not shown to be a
function of log dose level . Very few complaints were reported at either dose
level. No trend was found in incidence of complaints over the six injections
for either dose level. A single individual reported an injection site
reaction (prur1t1s} (Table 12), while systemic complaints occurring at
31431/3
000<>7
frequencies ~1% included fatigue/weakness (5%), nausea (2%), headache (1%) and
arthralgia (1%) (Table 13). A temperature of ~100°F (oral) was reported
following 4% of all injections (Table 8).
The three and six injection regimens in dialysis patients who rece1ved 20
or 40 mcg doses of vaccine in the deltoi~ or buttock were compared at each of
.the first three injections to determine if monthly injections caused greater
or fewer complaints than those spaced further apart. The only significant
difference found was in the incidence of systemic complaints after the second
injection in dialysis patients who received 40 mcg doses of vaccine. Ten
percent (2/20) of dialysis patients on the _six injection re.gimen had a
systemic complaint versus 0% (0/83) on the three injection regimen.
Although significant differences in complaint frequencies were found over
dose levels, they were not of clinical consequence. The incidence of any
clinical complaint was low. •
SUMMARY
Predialysis and dialysis patients did not respond to the vaccine as _well
as healthy adults. The response rate and level of anti-HBs attained after
three injections of vaccine does \ncrease with dose level, and it would appear
that responses are better 1f vaccine is administered in the deltoid rather
than the buttock. Preliminary data suggest that 100 mcg doses of vaccine may
induce antibody earlier than lower doses. Patients vaccinated under an
1ntens1fied six injection regimen did not respond better than those receiving
three injections of vaccine.
31431/4
1/22/86
Tlbl@ I
Antibody AHponses 11111119 Initially s.ron.t,,tiw Predlalnls Pa tle11ts lllo bcalwd

YNlt AKait,\-,\ Hepatitis I \lacclM (Thl"N 111.J-ctlon llegilll!ft)
Studln: 189, 811
' Ian
3 • 10-
.
,_ .,_,. .
DELTOID
Ian
l • JECTION
3a20..:a
GIi hllllllll l , se,__,.slan
3x40.:a
■1111111) -
IUTTOClt l!IJECTJON
3x 1 0 -
'
Clff ff
The ■IU/111 All ■llll'lll

SIii ar
■lllhll ■11111111
SIN or
■tu/lal
Clff
All 11IUl■l
'°" Clff C.IU/all
__,..,..rs
(lbS.J 5~2.1 ? Ill v«ch_, 5111?:Z. I ~ 10 S~2.1 ~ 10 .. ""
Vacclrwes 5111?:Z .1 ~ 10 S~Z.1 ~ 10 * Vacclllt!M 5~2 . ? 10 5111?:2.1
■lU/al
~ 10
All
Yaccl.-s
11111/Ml
S~Z . 1 ~ 10
I 0
(0/14)
D
(0/14)
0.3 --- --- 0
(0/28)
0
(0,211)
0.3
(14)
- -- 4
(1/29)
0
(0/28)
0.3
(13)
- -- 13
(111)
0
10/B) 0. 1 4.6
·--
3 0
(0/14)
0
(0114)
0.3 -- --- u
(6/21}
1
(2127)
o.s
(14)
90.0 90.0 23
(6/26)
12
(3126)
0.3
(12)
-- - :
• 0
(0/13)
0
(0/13)
0.3 -- 38
(8121)
Z9
(6/21)
1.0
(141
zu 23.6 42
(8119)
26
(5119)
1. 7
(12)
19.4 19. 4
119 IS
(2/13)
15
(l/13}
0.1 61 . 1 61 . 1 '8
(13/19)
58
( 11/19)
13 .8
(121
213 . 7 213. 7 67
(12118)
61
(11/18)
23 .6
(11)
120.9 IBli. 4
I
I
12 8 0 0.4 6.0 --- 11 so 8.S 18.5 18. S 40 40 3.3 111.3 111.3

(l/12) (0/12) CID/141 (1'14) (10) (4/10) 14110) (10)
.. Serol09lc results dttalned In Study 189 reported In SIN only.

tt GIils - rlzed abtalMd In Study 811 anl:,. (NI
C)
0
3125111 0-
112'2/8' -0
ell
fable 2
Antibody Responses lmong Initially seronegatlve Dlalxsis Patients

lh> Received Yeast Realfflb\nant ltepatltls B Vaccine ln the Oltltoid (Three Inject\on Regimen)
Studies: 816, 82S
3 ,c 20 11ea 3X40111CG 3 X 100 IIICQ

1, Seroconvers \on an 1111\J/lnH \ Seroc:onverslon G"1 (111IU/1111l · \ Seroconversion Gtn (S/Nl
- . rs - .
.
Time
~rs
111IU/111l All 11IU/11l mIU/1111 AU 11IU/11l 1111U/ln1 All Wlml
(flos.) S/M?:_2 . 1 ~ 10 Yacchiees S~2.1 ~ 10 S/~2.1 :: 10 Vaccinees S/~2.1 :: 10 S/~2.1 :: 10 Vaccinees S/~2 . 1 ~ 10
1 8 4 0. 4 S.4 18.S lS 8 0.6 8. 1 11.9 13 0 1.3 3.0 ---

(2/26) (1/26) (4/26) (2/26) (5/38) (0/38)
3 21 4 0.6 ft. 5 76 . 1 52 28 2.3 15.0 32.9 68 25 4. 4 8. 4 33.3

(5/24) (1/24) (13/25) (7125) (19/28) (7/28)
6 33 13 1.0 ft. 4 21. 7 81 63 10.8 21.5 35.2

(8/24) (3/24) (13/16) (10/16)
7/8 59 48 1.8 69.1 118.6 94 88 219.7 331.8 445.S

C17/29) (1 4/29) (16/17} ( 15/11)
12 52 41 5. 1 49.2 79.9 81 11 4 1.6 107.9 16S.6

( 15/29) (12/29) :(17/21) ( 15/21)
,
0
0
c,,
3 1251/4 "'
.c
1/S/Bfi
Table 3
Antibody Responses~ Initially Seronegatlve Dlal YSIS Patients Who Received

Yeast Aeca!t,inant Hepatitis 8 Vaccine I n The lluttoclr
Study 838
-
3 X 40 .:a 6 ,c 40 n:a 6 X 20 fflCG
I seroconversion GIil ■1tl/1111ltt
. rs
I Seroconverston GftT (ffllU/•1l t t I seroconverslon Gffl (ffllU/1111l t t
rs Resoonders
Time 111lU/11l Al l ■IU/111I 111lU/■l All 111IU/11l 111IU/ml AH 111U/lnl
(fm.) S/~2. 1 ~ 10 Vacctnees S~2.1 ~ 10 S/~2.1 ~ 10 Yaccinees S~2.1 ~ 10 5/~2.1 ~ 10 Vacclnees S/~2. 1 ~ 10
1 0
(0/48)
0
(0/48)
0.3 -- -- 0
(0/20)
0
(0/20)
0.3 -- --- 0
(0/20)
0
(0/20)
0.3 --- ---
3 35 22 1.3 16.5 31.0 35 20 1.2 11.4 33.5 32 26 1.2 23.6 31.4

(16/46) ( 10/46) (7/20) (4/20) (6/19) (5119)
6 34 29 1.4 26.1 33.8 69 69 32.2 189.8 189.8 56 44 9.1 81.3 190. 0

(12/35) (10/35) (11/16) ( 11/16) (9/16) (1/16)
~/8 64 58 12.3 90.2 115.5

(23/36) (21/36)
10 6S 54 12.8 13.8 117.6 61 60 6.1 24.S 21. 7 so 44 4.J ~5.0 55.0

(24/37) (20/37) ( 10/15) (9/15) (9/18) (8/18)
31251/3
1/5/85
0
....,
0
0
0
00701
Table 4
Percent of Predialysis Patients With Clinical Complaints*
During a Five-Day Period Following Vaccination With
Yeast Recombinant Hepatitis B Vaccine (Three Injection Regimen)
Studies: 789, 811

10 mcg Dose - Deltoid Injection
T~Re of Co!!!l!laint Dose 1 Dose 2 Dose 3 A11
Injection Site 0 (0/14) 0 (0/14) 0 (0/12) 0 (0/40)
Systemic 0 (0/14) 0 (0/14) 8 (1/12) 3 (l/40)
Any Local or Systemic Complaint 0 (0/14) 0 (0/14) 8 (1/12) 3 ( l /40)
Temperature ~lOO•F Oral 7 (0/14) 0 (0/13) 0 (0/11) 3 (l /38)

T~2e of Com2laint . Dose 1 Dose 2 Dose 3 All
Injection Site 18 (5/28) 11 (3/28) 5 (1 /20) 12 (9/76)
Systemic 18 (5/28) 14 (4/28) 10 (2/20) 15 (11/76)
Any Local or Systemic Co~plaint 29 ( 8/28) 21 (6/28) 15 (3/20) 22 ( 17/76)
Temperature ~1oo•F Oral 7 (2/27) 12 (3/26) 10 (2/20) 10 (7/73)

T:1t2e of Com2laint Dose 1 Dose 2 Dose 3 All
Injection Site 7 (2/27) 4 (1/26) 0 (0/17) 4 ( 3/70)
Systemic 4 ( 1 /27) e (2/26) 6 (1 /17) 6 ( 4/70)
Any Local or Systemic Complaint 11 (3/27) 8 (2/26) 6 (l /17) 9 ( 6/70)
Temperature ~1oo•F Oral 7 (2/27) 8 (2/26) 18 (3/17) 10 (7/70)
40 mcg Dose - Buttock Injection

Ty2e of Co~laint Dose 1 Dose 2 Dose 3 All
Injection Site 0 (0/8) Data Data 0 (0/8)

Systemic 0 (0/8) not not 0 (0/8)
Any Local or Systemic Complaint 0 (0/8) available available 0 (0/8)
Temperature ~100•F Oral 0 (0/8) 0 (0/8)
*A complaint 1s recorded here if it occurred during any fraction of the

five-day period following vaccination.
31091/2
1/10/86
00702
Table 5
Percent of Dialysis Patients with Clinical Complaints*

During a Five-Day Period Fo1101d1ng Vaccination With
Yeast Recombinant Hepatitis B Vaccine In The Deltoid
(Three Injection Regimen)
Studies: 816, 825

20 111eg Dose
TYRe of ComRla1nt Dose 1 Doie 2 Dose 3 All
Injection Site 8 (3/38) 0 (0/34) 0 (0/33) 3 ( 3/105)

Systemic - 24 (9/38) 3 (1/34) 12 (4/33) 13 (14/105)
Any Local or Systemic Complaint 29 (11/38) 3 (1 /34) 12 (4/33) 15 (16/105)
Temperature ~lOO•f Oral 5 (2/37) 0 (0/34) 9 (3/32) 5 (5/103)
40 mcg Dose
TYRe of Co!!!Rlaint Q2s~] DQ~e 2 Dose 3 All
Injection Site 11 (4/36) 3 ( l /34) 0 (0/24) 5 (5/94)
Systemic 22 (8/36) 0 (0/34) 8 (2/24) 11 ( 10/94)
Any Local or Systemic Complaint 25 (9/36) 3 (1 /34) 8 (2/24) 13 (12/94)
Temperature ~1oo•F Oral 11 (4/36) 3 (l /33) 0 (0/24) 5 (S/94)
100 11eg Dose

TYRe of C2J!!Rlaint Dose l Dose 2 Dose 3 All
Injection Site 9 (4/44) 8 (3/39) Data 8 (7/83)

Systemic 7 (3/44) 0 (0/39) Not 4 (3/83)
Any Local or Systemic Complaint 16 ( 7/44) 8 (3/39) Available 12 (10/83)
Temperature ~1oo•F Oral 7 (3/43) 3 ( 1/39) 5 ( 4/B2)
* A complaint 1s recorded here if it occurred during any fraction of the five-day

period following vaccination.
31101/1
1/2/86
Ta~,e 6
Percent of Dialysis Patients with Clinical Complaints*

During a Five-Day Period Following Vaccination
with Yeast Recoflbinant Hepatitis 8 Vaccine 1n The Buttock
Study 838
3 x~~Q mcg Dose
l~Re of C2!JmliiDt Dose 1 Dose z Do~e 3 All
Injection Site 0 (0/51) 0 (0/49) 0 (0/38) 0 (0/138)

Syste111c 8 (4/51) 0 (0/49) 3 (l/38) 4 (5/138)
Any local or Systeai c Complaint 8 ( 4/51) 0 (0/49) 3 (1/38) 4 (5/138)
temperature ~1oo•F Oral 4 (2/51) 0 (0/48) 3 (1/38) 2 (3/137)
6 x 40 111tg Dose
lYRe of tglaint Dose 1 Dose 2 Dose 3 Dose 4 Dose 5 Dose 6 ALL
Inj ection Site 0 (0/20) 0 (0/20) 0 (0/20) 0 (0/19) 0 (0/19) 0 (0/16) 0 (0/114)
Systemic 15 (3/20) 10 (2/20) 15 (3/20) 16 (3/19) 0 (0/19) 0 (0/16) 10 ( 11 /114)
Any Local or Systeaic C0111pl1int 15 (3/20) 10 (2/20) 15 (3/20) 16 (3/19) 0 (0/19) 0 (0/16) 10 ( 1 l /114)
temperature~ 1oo•F Oral** 10 (2/20) 5 ( 1/19) 5 (1/19) 0 (0/18) 6 (l/18) 7 ( 1/15) f, ( f,/109)
fl x 20 flcg Dose
type of C0111plaint Dose 1 Dose 2 Dose 3 Dose 4 Dose 5 Dose 6 AU

Injection Site 0 (0/20) 0 (0/20) 5 (1/20) 0 (0/20) 0 (0/20) 0 (0/17) 0. 9 ( 1/117)
Syste1111c 5 (1/20) 10 (2/20) 5 ( 1/20) 5 (1/20) 0 (0/20) , 0 (0/17) 4 (5/117)
Any local or Syste~1c Complaint 5 (1/20) 10 (2/20) 10 (2/20) 5 (1/20) 0 (0/20) 0 (0/17) 5 ( 6/117)
Temperature ~1oo•F Oral 6 (1 /18) 0 (0/19) 0 (0/20) 5 (1/20) 0 (0/20) 0 (0/16) 2 (2/113)
*A complaint is recorded here 1f it occurred during any fraction of the five-day period following. vaccination.
**Fever was reported in one vaccine recipient (temperature not recorded) 0
....,
0
0
31111/1 .....
1/8/86
00704
Table 7
Frequency of Local and Systemic Complaints

Among Predialysis Patients During a
Five-Day Period Following 186 Deltoid Injections of
Studies: 789, 811

Nunt>er of Vaccine Recipients: 69
Body System/ S Frequency Body System/ % Frequency

Conplaint (Number) C011pla1nt (Number)
Local/Injection Site 6 (-11) Musculoskeletal 1 (2)
Soreness 6 (11) Arthralgia, Other 0.5 ( l)

Stiffness/Tightness 2 (3) Shoulder Pain 0.5 (,)
Ecchymosis 0.5 ( 1) Knee Pain 0.5 ( 1 )
Pain 0.5 (l)
Swelling 0.5 ( 1 )
Whole Body/General ~ (5) Psychiatric/Behavioral 1 (2)
Chi 11 s l (2) Depression 1 (2)

Headache 1 (2)
Fatigue/Weakness 0.5 (l)
Sensation of Warmth 0.5 ( 1) Nervous System 0.5 (1)
General
I 11 ness, Nos 0.5 ( l) Somnolence 0.5 (1)
Digestive 3 (5}
Nausea 3 ( 5)
Vomiting 0.5 (1)
Abdominal Tenderness 0.5 ( 1)
Resp1 ratory 2 (4)
Upper Respiratory 2 ( 3)
Infection, Nos.
Pharyng1 tis 0.5 (1)
wva/31511/9
1/9/86
00705
Table 8
Percent (Number) of Predialysis Patients With
Specific Systemic Complaints During a Five-Day Period Following
18& Deltoid Injections of Yeast Recombinant Hepatitis B Vaccine
Studies: 789, 811
Number of Vaccine Recipients: &9
Complaint Frequency 1-3%

Nausea 3 (5)
Upper Respiratory Infection, Nos 2 (3)
Chills 1 (2)
Depression 1 (2)
Headache 1 ( 2)
Cogpla1nt Frequency <11

Abdominal Tenderness 0.5 (1)
I 11 ness, Nos 0.5 (1)
Knee Pain 0.5 (1)
Pharyng1t1s (Sore Throat) 0.5 (1)
Shoulder Pain 0.5 (1)
S011nolence 0.5 (l)
Fatigue/Weakness 0.5 (1)
Arthralgia 0.5 (1)
Sensation of Wan11th, General 0.5 (lf
Vomiting 0.5 (1)
wva/31621/5
1 /10/86
00700
Table 9
Among D1alys1s Patients During a Five-Day Period Following
341 Injections (Deltoid or Buttock) of Yeast Recombinant Hepatitis B Vaccine
Studies: 816 , 838

Body System/ ,: Frequency Body System/ % Frequency

Complaint (Nulllber) Complaint (Nulllber)
Local/Injection Site 3 (10} Musculoskeletal Llil

Soreness 2 (7) Arthralgia, Other 0.2 (1)
Ecchymosis 0.5 (2) Arthralgia, 0.2 (1)
Pain 0. 5 (2) Mono-articular
Stiffness/Tightness o. 5 (2) Arthritis 0.2 (1)
Ann Pain 0.2 (1)
Whole Body/General s c11 l Hand Cramps 0.2 (1)
Muscle Cramps 0.2 (1)
Headache 1 (5)
Chills 1 ( 4)
Sensation of warmth. o.5 (2) Nervous System 0.8 (3)
General
Lightheaded 0.5 (2) Dizziness 0.5 (2)
Illness, Nos 0.2 (1) Tremor 0.2 (1)
Malaise 0.2 (1)
Digestive Llll Infections Syndromes 0.2 (1}
Nausea 0.8 (3) Influenza, Nos 0.2 (1)

Vomiting 0. 5 (2)
Increased Appetite 0.2 (1)
Diarrhea 0.2 (1)
Psychfatric/Behavforal 0.2 (1)
Respiratory 0.8 (3) Insomnia/Disturbed 0.2 (l)
Pharyngitis 0.2 (l)

Upper Respiratory 0.2 (1)
lnfect1on, Nos Cardiovascular 0.5 (2)
Bronch1t1s, Nos 0. 2 (1)
Hypertension 0.2 (1)
Other 0.2 (1)
31511/7
1 /21 /86
00707
Table 10
Percent (Number) of Dialysis Patients With
Specific Systemic Complaints During a Five-Oay Period Following
341 Injections (Deltoid or Buttock) of Yeast Recombinant Hepatitis B Vaccine
Studies: 816, 838
c011pla1nt Frequency 1-21

Headache 1 ( 5)
Ch1lls 1 (4)
Complaint Frequency <1% (Number)

Nausea 0.8 (3)
Lightheaded 0.5 (2)
Sensation of Warmth, General 0.5 (2)
Dizziness 0.5 (2)
Vomiting 0.5 (2)
Appetite Increased 0.2 (1)
Arm Pain 0.2 (1)
Arthralg1a, Other 0.2 (1)
Arthralgia, Monoarticular 0.2 (1)
.Arthritis, Other 0.2 (1)
Bronchi.tis 0.2 (1)
Diarrhea 0.2 (l)
Hand Cramps 0.2 (1)
Hypertension 0.2 (1)
Illness, Nos 0.2 (l)
Influenza, Nos 0.2 (1)
Insomnia/Disturbed Sleep 0.2 (l)
Malaise 0.2 (1)
Muscle cramps 0.2 (1)
Pharyngitis (Sore Throat) 0.2 (1)
Tremor 0.2 (1)
Upper Respiratory Infection, Nos 0.2 (1)
Other 0.2 (1)
wva/31621/6
1/10/86
00708
Table 11

Among Dialysis Patients During a Five-Day Period
Following 83 Deltoid Injections of Yeast Recombinant Hepatitis 8 Vaccine
Containing 100 11tg HBsAg (Three Injection Regimen}
Study 825
Nuraber of Vaccine Recipients: 44
Body System/Complaint %Frequency (Number)
Local/Injection Site .!Lill

Soreness 7 ( 6)
Erythema 1 (1)
Inflannation 1 ( l)
Prurit1s 1 ( 1)
Stiffness/Tightness 1 (2)
Whole Body/General Lill

Fatigue/Weakness l ( l)
Other l ( l)
Respiratory Lill
Pharyng1th l ( 1)
Cough 1 ( l)
Musculoskeletal Lill
Arthralgia, Other 1 (1)
31511/8
l /12/86
Table 12
Frequency of Local and Systemic Complaints Among Dialysis Patients
During a Five-Day Period Foll01,1ing 231 Buttock Injections of
{Six Injection Regimen)
Study 838
Body Systera/ % Frequency Body System/ % Frequency

C2!!1!laint (Number} Coraplaint {Number}
Musculoslc.eletal 1 ( 3}
Local/Injection Site 0.4 '1}
Arthralg1a, Other 1 (3)
Pruritis 0.4 (1)
Psychiatric/Behavioral 0.4 Pl
Whole Body/General r, (15}
Depression 0.4 (1)
Headache 1 (3)
Illness, Nos 0.4 ( 1) Cardiovascular 0.8 (2}
Lightheaded 0.4 ( 1)
Chills 0.4 (1) Hypotens1on 0.4 (1)
Other 0.4 (1)
Digestive 3 ,01
Nausea 2 (4)
Diarrhea 0.8 (2)
Abdominal Pains/ 0.4 (1)
Cramps
Diminished Appetite 0.4 ( l)
Respiratory 0.4 ,11

Cough 0.4 (1)
31621
1/10/86
00710
A P P E ND I X 1
S TAT I S T I CA L ME T H O D S
3124I/11
1/21/86
00711
All tests of significance were two-sided at 0.05 significance level.
A. Clinical Compliints
1. The incidence of the various clinical complaints in dialysis
patients . on the three dose regimen. healthy teenagers and healthy
ll-1antel-Haenszel Testl for trend.
2. All other differences in the incidences of the various clinical
complaints in dialysis patients due to dose level or regimen and
in health care personnel receiving vaccine from consistency lots
adults. healthy teenagers and health~ children wu analyzed over
studies using the Mantel Haenszel Test for trend.
2. Differences 1n seroconversion rates in healthy adults due to age
or sex were evaluated over studies using the Mantel Haenszel
3. Differences in seroconversion rates due to age in healthy
children, dose level in dialysB patients, and vaccine lot in
Chi-Square.
C. level of Response (Titers)

The effect of age, sex, lot (consistency lots only 1n Study 880). or
dose level (all other studies) in health care personnel and other
age in healthy children, and of dose level and regimen in dialysis
antigen were assigned a titer of 0.3 mIU/~l ·in the analysis.
REFERENCE
1. Tarone RE, Ware J: On Distribution-Free Tests for Equality of
Survival Distributions. Biometrika 64: 156-160, 1977.
31241/12
00712
Dialysis and Predialysis Patients
Study 789 - Durham. NC - Dr. G. Hamilton
The study population consists of adults with. chronic renal insufficiency

(pre-dialysis) who are negative for hepatitis B serologic markers.
Participants receive either 20 mcg or 40 mcg injections of yeast recombinant
vaccine lot C-k446 or 40 mcg injections of plasma-derived vaccine lot 2449H or
1885K. All injections are administered at 0, 1, and 6 months.
Fifteen participants have received two 40 mcg injections of yeast recombinant

vaccine and seven of these have received the third injection. At 7/8 months ,
71 % (5/7) of these vaccinees seroconverted for anti-HBs (S/N ~2.1).
Fifty-seven percent (4/7) developed protective levels of anti-HBs (S/N ~10) .
The GMT for all vaccinees at that ttme was 12.7 S/N and 60.2 for responders
(S/N ~10).
Fourteen subjects have received two 20 mcg injections of yeast recombinant
vaccine and seven of these have received the third injection. Eighty-six
percent of the vaccinees seroconverted for anti-HBs (SIN ~2.1) at 7/8 months.
Fifty-seven percent (4/7) developed protective levels of anti-HBs (S/N ~10).
The GMT for all vaccinees at that time was 25.3 S/N and 130.0 for responders
(S/N ~10).
Sixteen predialysis patients have received two 40 mcg injections of plasma
derived vaccine. S1x of these have been administered the third injection. At
7/8 months, 67% (4/6) of the subjects seroconverted (S/N ~2.1) and developed
protective levels of anti-HBs (S/N ~10). The GMT for all vaccinees at that
time was 27.7 S/N and 168.6 for responders (S/N ~10).
No serious or alarming adverse experiences attributable to either vaccine have

been reported. The study continues in progress.
~tudy 811 - Switzerland - Dr. P. Grob
Predialysis patients and health care personnel are enrolled fn Study 811.
Predfalysis patients are assigned to one of five groups and receive yeast
recombinant vaccine lot C-K446 or plasma-derived vaccine (Heptavax) lot
1510J. Group 1, 2, and 3 participants receive 10 mcg, 20 11eg, and 40 mcg
injections of yeast recombinant vaccine, respectively. Group 4 and 5
participants receive 20 mcg and 40 mcg injections of plas11a-der1ved vaccine,
respectively. The vaccine 1s administered at 0, 1, and 6 months for all
groups.
Fourteen predialysis patients (group l) have received two 10 mcg injections of

yeast recombinant vaccine and 13 of these have rec e ived the third Injection.
At 7/8 months, 15% (2/13) of the subjects seroconverted (S/N ~2. 1) and
developed protective levels of anti-HBs (mIU/ml ~10). The GMT for all
31511/1
1/10/86
00713
Study 811 - Switzerland - Or. P. Grob CCont . l

vaccinees was 7 .0 mIU/ml and 67. 7 for responders (mIU/111 ~10). No patient
tested. seroconverted before 7/8 months.
Fourteen predialysis patients (group 2) have received two 20 mcg injections of
yeast recombinant vaccine and 13 of these have received the third injection.
· At 7/8 months, 58% (7/12) of the subjects se roconverted (S/N ~2.1} and
developed protective levels of anti-H8s (mIU/ml ~10). The GMT for all
vaccinees was 13.8 mIU/ml and 213.7 for all responders (mIU/ml ~10).
In group 3. thirteen pred1alys1s patients have received two 40 mcg injections
of yeast recombinant vaccine. Twelve of these have been administered the
third injection. Sixty-four percent (7/11) seroconverted (S/N ~2.1) for
anti-HBs at 7/8 months. Fifty-four percent (6/11) developed protective levels
of anti-HBs (mIU/1111 ~10). The GMT for all vaccinees at that time was 13.6
Eleven predialys1s pathnts (group 4) have received two 20 mcg injections of
plasma-derived vaccine and 10 of these have received the third injection. At
7/8 months, 25% (2/8) of the subjects seroconverted (S/N ~2.1) and developed
protective levels of ant1-HBs {mIU/ml ~10) . The GMT for all vaccinees was 1.3
In group s. 11 predialys1s patients received two 40 l'IIC9 injections of
plasma-derived vaccine and 10 of these have received the third injection.
Fifty percent {4/8) of the patients seroconverted for anti-HBs (SIN ~2.1) at
7/8 months. Thirty-eight percent (3/8) developed protective levels of
anti-HBs (mIU/ml ~10). The GMT for all vaccinees at 7/8 months was 8.7 mIU/ml
and 791.5 for responders (mIU/ml ~10).
There have been no serious or alarming reactions attributable to vaccine. The
study continues in progress. Refer to the sunmary on health care
personnel/healthy adults for data regarding other subjects vaccinated in this
study.
Study 816 - Ph11adelph1a, PA - Dr. S. Plotkin and Dr. S. Starr

The study population cons~sts of health care personnel and adult hemodialysis
patients (including hemodialysis patients who were previous non-responders to
plasma-derived vaccine). Health care personnel received 10 mcg injections of
yeast recombinant vaccine lot C-K446. · Dialaysis patients received either
20 mcg injections (group 1) or 40 mcg injections (group 2) of yeast
recombinant vaccine lot C-K446. All vaccine is administered at O, 1, and 6
months.
Thirty-nine hemod1alysis patients (group 1) have received one 20 mcg injection
of vaccine. · Thirty-four of these have received the second injection and 32
the third injection. At 7/8 months. 571 (16/28) of the patients seroconverted
31511/2
1/10/86
0071'!
Study 816 - Philadelphia, PA - Dr. S. Plotkin and Dr. S. Starr (Cont.)

for anti-H8s (SIN ~2.1). Forty-six percent (13/28) developed protective
levels of anti-HBs (mIU/ml ~10). The GMT for all vaccinees at 7/8 months was
7.5 mIU/ml and 132.4 for responders (mIU/~1 ~10).
In group 2, 36 dialysis patients have received one 40 mcg injection of vaccine
and 34 of these have received the second injection. The third · injec"tion has
been administered to 24 patients. Eighty percent (16/20) of these patients
seroconverted for anti-HBs (S/N ~2.1) at 7/8 months. Seventy-five percent
(15/20) developed protective levels of anti-HBs (mIU/ml ~10). The GMT for all
vaccinees was 81.8 mIU/ml and 418.4 for responders (mIU/m1 ~10).
No serious or alarming reactions attributable to vaccine have been reported.
The study continues in progress. Refer to the sunmary on health care
personnel/healthy adults for data regarding other subject vaccinated in this
study.
Study 825 - Bethesda, MD - Dr. H. Alter

The study population consists of adult hemodialysis patients who are negative
for hepatitis B serologic markers. Dialysis patients who were nonresponders
to previously administered -plasma-derived vaccine may also be included in the
study population. Participants receive a 100 mcg injection of vaccine lot
C-L915 at 0, 1. and 6 months.
Forty-four hemod1alysts patients have received one 100 mcg injection of
vaccine and forty-one of these have received the second injection. No subject
has yet received the third injection of vaccine. Serology data are available
through 3 months of follow-up. Sixty-eight percent (19/28) of the patients
seroconverted for anti-HBs (S/N ~2.1) at 3 months. Twenty-five percent (7/28)
developed protective levels of anti-HBs (mIU/ml ~10). The GMT for all
vaccinees at 3 months was 4.4 S/N and 33.3 for responders (S/N ~10).
No serious or alaming reactions attributable to vaccine have been reported.
The study cont,nues in progress.
Study 838 - West GennanY - Or. F. Deinhardt

The population of STudy 83B consists of adult hemodialys1s patients,
pred1alys1s patients and health care personnel. Yeast recOllbtnant hepatitis e
vaccine lot C-K733 1s being utilized. Dialysis patients may receive 40 mcg
injections at 0, 1, and 6 months, or 20 or 40 mcg injections of vaccine at o.
1, 2, 3, 4, and 6 months. Predialysis patients receive either 10 mcg or 40
mcg 1nject1ons of vaccine at 0, l, and 6 months. All injections were
administered in the buttock.
Fifty-one dialysis patients have been enrolled in the three 40 mcg injection
regimen. All 51 patients have received two 40 mcg injections and 48 of these
have received the third injection. At 7/8 months, 64% (23/36) of the patients
seroconverted for anti-HBs (S/N ?2.1). Fifty-eight percent (21/36) developed
3151 I/3
1/10/86
00715
Study 838 - West Germany - Or. F. Deinhardt (Cont.}

protective levels of anti-Hes (mIU/ml ~10). The GMT at that time for all
vaccinees was 12.3 mlU/ml and 115.5 for responders (mIU/ml ~10).
Twenty dialysis patients have been enrolled in the six 40 IICg injection
regimen. All 20 subjects have received the first three injections and 19 of
these have received the fourth and fifth injections. Seventeen patients have
been administered all six 40 mcg injections of vaccine. At 10 months. 67%
(10/15) of the patients seroconverted for anti-HBs (S/N ::2.1). Sixty percent
(9/15) developed protective levels of anti-HBs (mIU/ml >10). The GMT at 10
months for all vacc1nees was 6.7 mIU/ml and 27.7 for responders (fflIU/ml ~10).
Twenty dialysis patients in the six 20 mcg injection regimen have all received
five injections of vaccine. Seventeen of these have received the sixth
injection. Fifty percent (9/18) of the patients seroconverted for anti-HBs
(S/N ::2.1) at 10 months. Forty-four percent (8/18) developed protective
levels of anti-HBs (mIU/ml ~10) at that ti111e. The GMT for all vaccinees was
4.7 mIU/ml and 55.0 for responders (mlU/ml ~10).
Eight predialysis patients have been enrolled in the three 40 mcg injection
regimen. All eight patients ha~e received the first two injections of
vaccine. None has yet received the third injection. Serology data are
available through one month of follow-up. Thirteen percent ( 1/8) of the
subjects . seroconverted for anti-HBs (S/N ~2.1). The GMT for all vaccinees was
0.7 mIU/ml and 4.6 mIU/ml for responders (S/N ~2.1). None of the participants
developed protective levels of anti-HBs (mIU/ml ~10) at one month.
reported. The study continues in progress. Refer to the sunmary of health
care personnel/healthy adults for data regarding other subject vaccinated in
thh study.
3151 I/4
1 /10/86
Cf\
00
,..._
>-
0
~
t-
V')
00716
PURPOSE: To compare. antibody and cl 1n1cal responses to plasma

and yeast recombinant vaccines at 2 dose levels among
uremic patients not yet undergoing dialysis who are
negative for HBV -markers.
VACCINE: Yeast Recombinant Hepatitis B Vaccine Lot #974/C-K446

(20 mcg HBsAg/ml)
HEPTAVAX Plasma-Derived Hepatitis B Vaccine
Lot 2449H (20 mcg HBsAg/ml)
Lot 1885K (20 mcg HBsAg/ml)
PRINCIPAL John Hamilton, M.D.

UIVESTIGATOR: VA Medical Center
Durham, NC 27705
SECONDARY Joan Drucker, H.D.

INVESTIGATOR: Division of Infectious Diseases
Duke University Medical Center
Durham, NC 27710
Robert Gut111an, M.D.
Division of Nephrology
·Duke University Medical Center
Durham, NC 27710
STUDY LOCATION: Duke University Medical Center

Durham, NC 27710
Veteran's Administration Medical Center
508 Fulton Street
Durham, NC 27705
DATE INITIATED: May 23, 1984
STUDY PROCEDURE: The study population consists of 45 adu 1ts of et ther

sex, aged 16-60 years, who have chronic rena 1
insufficiency not severe enough to requ1 re d1a l ys 1s
(creat1n1ne levels of 2.0 mgm/dl or greater), who are
negative for HBsAg, ant1-HBc and anti-HBs, and have a
normal ALT level.
24051/1
l /19/86
00717
Study 789
STUDV PROCEDURE To assure that patients in the treat111ent groups

(CONT.): are similar, assign111ent to vaccine and dosage is
stratified by sex, age and creatinine level.
Participants are randomly assigned to one of the
following groups.
~ vaccine ~ ~ Raaillllfl
Lot 974 14 20 IIC9 1 - 1.D ■1 intr..,scular

injection on dly o, 1 110.
ind 6 .:,S,
2 Lot 974 15 40 111e9 2 - 1.0 ■1 intr11111Uscular

injections on dly o, 1 110.
and' al)$.
3 1£PTAYAK 16 40 IIICg 2 - 1.0 •1 lntr-.scular
Lot 2U9H injections on day O, 1 110.
or and 6 .-s.
Lot 1&3SIC

for 5 days after each injection a·nd also to record any
local or systemic complaints they may have during this
period.
participant approximately 2 weeks before the first
obtained at 1, 3, 6, 7, 9 and 12 1110nths. The samples
are assayed for HBsAg, anti-HBc, anti-HBs, ALT, and
creatinine. Samples with ant1-HBs titers >25 ■ IU/ml
may be tested for the proportions of anti-! and anti-g_
activity. Samples may be tested for yeast antibody at
MSDRL.
RESULTS: Pre-Dialysis Patients:

2D 11eg Lot #974/C-K446 at 0, 1, and 6 110nths
40 mcg Lot #974/C-K446 at 0, l, and 6 110nths
40 mcg HEPTAVAX Lot #2449H at 0, 1, and 6 months
40 mcg HEPTAVAX Lot #1885K at 0, 1, and 6 months
24051/2
1 /19/86
00718
Study 789
RESULTS (CONT.) : 1. Number vaccinated:
--Injection ~ r - - -
Dow Level _1_ -·_2_ __3_
40 i;;cg Recoim i l'WI t IS IS 7

20 111:g ReCIJllbiMnt 14 14 7
40 cg PIHIIII 16 16 6
Serologic data at 7/8 months are

available for 7, 7, and 6 recipients of
40 mcg recollbinant, 20 mcg recombinant,
and 40 mcg doses of plasma-derived
vaccine, respectively. The following
antt-HBs responses were observed at that
ti111e. Table 1 shows seroconvers1on
rates and GMTs for up to one year of
follow-up.
I with Anti-'lls GNT {SIN)

Dose Level S/N ~2- 1 SIN ~10 Viccineas SIN ~2.1 SIN ~10
40 IIICQ Aecaltlin&nt 71 (5/7) 57 (4/7) 12. 7 35. 4 60.2

20 incg Rec:alDinant 86 (6/7) 57 (4/7) 25.3 43 ..4 130.0
40 IIICg Pl •SIIII 67 (416) 67 (4/6) 21.1 168.6 168.6
3. Clinical Complaints
and 7 participants following the first, second,
and third injections of 40 11eg recombinant
vaccine; 14, 14, and 7 participants who received
20 mcg recombinant vaccine; and for 16, 16, and 6
who received 40 mc-g of plas111a vaccine.
24501/3
1/23/86
007tq
Study 789
RESULTS (CONT.): Clinical complaints and maximum temperatures
reported follok11ng each injection are provided 1n
Tables 2-7.
Type of F~cy in \ by Injection No.

<;aiplaint Dose L~I 1 2 3
Injection .0 q Aecalibhiant 13 (2/1S) 7 C1/1S) 0 (0/7)

Site 20 IIC!I Aecallbinant 36 (S/14) 14 (2/14) 14 (1/7)
.0 IIIC!I Pl aaaa 6 (1/16) 6 (1/16) 17 (1/6)
Systanic .O 11e11 Aecaa>inant 7 (1/15) 13 (2/15) 14 (1/7)

20 111eg Aeca!Dinant 29 (4114) 29 (4/14) 29 (2/7)
.0 IICII P1&9111 6 (1/16) 13 (2/16) 17 (1/6)
ALT Elevations
Vaccine recipients included one person in the 20 nacg
recombinant group who had a pre-vaccination ALT level
2-3 times the upper limit of normal. His ALT level
reniained elevated through 9 110nths of follow-up but
had dropped to normal at his one year bleeding. He
re111ained negative for HBsAg and has shown no signs of
infection. There was also one person in the 40 mcg
plasma group and one in the 40 racg recOlllbinant group
with normal pre-vaccination ALT levels who had
transient elevated ALT levels approximately 1.5 - 2
times the upper limit of normal 2 months after the
first dose of vaccine. All subsequent ALTs were
normal. These subjects have not shown any clinical or
serologic signs (HBsAg or anti-HBc) of hepatitis B.
Adverse Reactions Reported to OoBRR
Case t5 ID a 30-year old male, died on (6) (6) fr011
he110rrhage of esophageal varices and subsequent
complications. He had received two 40 11eg
i11111unizations of plasma-derived vaccine Lot 2449H, on
rnr-
{I>) and on (b B) The patient had a history of
polycyst1c kidney ana 11ver disease, as we11 as
previous episodes of variceal bleeding. The death 1s
not believed to be vaccine related.
Case b 6~ a 58-year old male, had a history of
hypertension and chronic . renal failure (predialysis).
24051/4
1/23/86
hb1e 1
Antibody Responses llmng Pre-Dialysis Patients Following Vaccination vith 40 or 20 l'llC9

Doses of Recait,lnant Hepatitis 8 Vaccine Lot 1914/C...«446 or 40 11eg Dose$
of P1aSlllil Vaccine lot 2449H or lot 1885l at o. 1, and 6 ttonlhs
in Study 189
40 IIIC!I Rec:onC, i Mnl 20 g Rec:a,b\nant 40 .:g P1aSIIIII

1, with Anti_.s _ _ ~ Giff (SIN) \ with Anti_.s GIIT (SIN) \ 1tl th Anti-h9s GIIT (SIN)
Resoonders Re~Mler-s Re~Mlers
Ti• SIN ,m SIN SIN All SIN sm AH SIN
(flos.) S/~2. 1 ::, 10 Vac:c lnees S/~2.1 ~ 10 S/~2.1 ~ 10 VaccilM!es S~2.1 ~ 10 5~2.1 ~ 10 v~ccint!es 5~2.1 ~10
1
(1115)
0
(0/15)
1.0 5.1 -- 0
(0/14)
0
(0/1 4)
0.8 - --- 13
(2/16)
0
(0/16)
1. 1 4.1
3 43 21 3.4 12.4 29.3 38 8 2.3 1.8 26. J 61 40 5.9 14.1 30.2

(6/14) (3/14) (5113) (1/13) (10/15) (6/15)
6 43 0 1.1 4 .1 -- 57 29 3.0 1.4 21. 4 60 60 6.9 31.8 31.8

(311) (0/7) (4/7) (211) (3/5) (3/5)
1 71 51 12.7 35.4 60.2 86 51 25.3 43 .3 130.0 61 61 21.1 168.6 168.6

(511) (411) (6/7) (411) (416) (416)
9 100 100 12.6 12.6 12.6 100 33 '1 4.9 14.9 141.2 100 100 73.8 73.8 73.8
(1/1) (111) (313) (1/3) (2/2) (2/2)
12 100 25 6.0 6.0 33.3

(4/4) (1/4)
0
0
.....
"'
0
Table 2
PATIENT COUHT CLINICAL CotlPLAlNTS
RECOl18INANT HEPATITIS 8 VACCINE
LOT ICK446
STUDY 0789
TREAlNENT
DOSE 20 MCG
PATIENT CLASS: PRE-DIALYSIS PATIENTS

1----------------------------------------------------------------------------I
I DAYS POST VACCitlATION • HUl18EA
CLINICAL
COMPLAIHTS I
•
O • l
I
I 2 I
I
3 • 4
•
I 5 •
,
•----------------------------------------------------------------------------•
,
I
MITH
,
.COflPlAIHTS
......................................................... ...•......•.......... .......... .......... ..........•..........
I
,
I I
REACTIOH, LOCAL (INJECT. SITEI I S I 1 I O I O I O I O I I 5
I l 35.7l0 • I 7.llO I I 0.0¼1 I I O.OZ) I ( O.OZI • ( o.o:o I I I 35.7i0
-----------------------------------1----------l----------1----------l----------l----------l----------•----------l-----------
sORENESS I 5 I l I O I o I O I o I I 5
I, u.no I, 1.uo I, o.or.1 I, o.o;o I, o.o:o 1·, o.oz1 I I, 35,7;0
I I I I • I I I
SMELLING • l • 0 I O I O I O I O • • 1
• I 7.lZl • ( D.OZI I I o.o;o I I o.o:o I I 0.0¼1 I l o.DiO I I I 7.Un
I I I I I I I I
STIFFNESS/TIGHTNESS I 1 I O I O I O I O • O • I 1
I I 7.1¼1 I ( O.O¼l • I 0,01.I I ( O.OZl • I 0.01.I I I O.OZI • • ( 7.lZI
-----------------------------------•----------•----------•----------1----------l----------l----------l----------l-----------
svsnr11c • 1 I 1 • l I 1 • t I 1 I I 4
I l 7,lZI I ( 7.UO I I 7.lZI I ( 7.lZ) I I 14,3ZI I I 7.UO • • l 1!8.6i0
RESPIRATORY I 0 0 0 I 0 l I 0 l
( O.OXI ( O.OZI ( o.or.1 I 1 O.OZ) •I ' 7.liO I l O.OY.I I 7.lZI
I I
UPPER RESPIRATORY INFECT., HOS. 0 0 0 I 0 I l I • 0 l
( I.OZ) ( O.OZI ( O.OZI I l o.oz, • ' 7.liO I l O.OY.I I 7.liO
I I I
KJSCULOSl<ELETAL I l 0 l I l I l 1 t
( 7. lZ) ( O.OZI ( 7.lZI I I 7.IZJ I I 1.1:0 •I < 7.lY.J I 14.3%1
I I
ARTHRALGIA IOTHERI I 0 0 1 I 0 I 0 I• 0 1
I < O.DZI ( o.o:o ( 7.lZI I I 0.0¼1 • I O.OiO I I O.OZI I 7.1%1
I I I I
SHOULDER PAIN 1 0 0 I 0 I 0 I 0 1
•I 7.lZI ( o.o:o ( o.D%1 I I o.o:o I I O.OY.I I I 0.01.1 I 7.1%1
I I
l<N£E PAIN I 0 0 I 1 • 1 I 1 l
O.OiO
0
O.OiO ( o.or.1 I I 7.17.J •
I I 7,liO I I 7 . lY.J 7.lZI
'
(
II ' I I I I
NERVOUS SYSTEH I a I 1 0 I 0 I 0 I 0 1
0.07.) • ( 7.lr.l ( Cl .OY. I • ( 0.01.1 I I o,o;o I < O.OY.I I. 7.lZI 0
0
.....
...,
-"'
Table 2 (cont.)
PATIENT CDl»IT CLINICAL COl1PLAIHTS
RECOHBINAHT HEPATITIS B VACCltlE
LOT I CK446
STUDY 0789
TREATt1£HT
DOSE 20 t1CG
PATIENT CLAss: PRE-DIALYSIS PATIENTS
I TOTAL VACCINEES I 1ft PATIENTS I - OOSE l I

t----------------------------------------------------------------------------1
I DAYS POST VACCitlATJOU I NUMBER
l----------------------------------------------------------------------------1
CLINICAL
COl1PLA1NTS
......................•............ ,
I
I
O I
,I
1 I
I
, 2
.
I
I
,
3 I
I
if
, I
I
5
,
I
I
, ,
WITH
ICOtlPUINTS
.......... .......... .......... .......... .......... .......... .......... ...•......
I
SOl'IHOLENCE I O I l I O I O I O I O I I l
I I 0 . 01.1 I I 7.1%1 I I 0.0%1 I I 0.01.1 I I 0.01. 1 I c 0 . 01.1 I I I · 1.11.1
-----------------------------------1
PERSOHS WITH COHPU IHTS I
----------1----------I----------I----------I----------I----------
6 I 2 I l· I l I 2 I l
I----------I-----------
I I 7
I I 42,9)(1 I I 14 . 3i0 I I 1 . 1;0 I C 7 . 11.1 I C llf . 31.1 I ( 7 . liO I I ( so.o;o
-----------------------------------t----------1----------1----------1----------I----------I----------I----------I-----------
PERSONS WITH HO CONPUINTS I a I 12 I u I n I 12 I n I I 7
11 57.liO IC 85 . 7)(1 IC 92.9%),. '12.9i0 11 85.77.1 IC 92 . 91.I I I Cso .o;o
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WI TH NO DATA I o I I I O I O I O I O I I D
I c 0.0%) I I 0.01.1 I I 0 . 01., I I 0.01.1 I I 0.01.t I I 0.01.1 I I 1 · 0 . 01.1
0
0
....
rv
"'
-
Table 2 (cont.)
PATIENT CotMT CLIHICo\L COMPLAUITS
RECOtt81NAHT HEPATITIS B VACCJHE
LOT I CK446
STUOY 0789
TREATHEHT
DOSE 20 ntG
PATIENT CLASS! PRE-DIALYSIS PATIENTS
I TOTAL VACCIHEES t lt+ PATIEHTSJ. - DOSE 2 I

1--------------------------------------------------------
I Do\YS POST VACCINATION
·-------------------1I t,\JMBER
CLINIC AL 1----------------------------------------------------------------------------I WITH
COt1PU INTS I O I 1 I 2 I 3 I 4 I 5 I I COt1PUIHTS
•••••••••••••••••••••••••••••••••••l•••••'°'•••l•••••••••• l••••••••••l•••••••••• l•••••••••• l•••••••••• l•••••••••• l•n••••••••
I I I I I I I I
REACTION , LOCAL I UIJECT. SITEI I 2 I O I O I O I o I O I I Z
I I 14 . lr.) I I O.Or.) I I O.Or.) I t O. Or.) I I 0.01.) I I O. OY.) I I I 14.3%1
----------------------------------- 1----------I----------I----------I----------I----------I---------- I----------I-----------
SORENESS I 2 I o I o I o I o I o I I 2
I l 14.lr.1 I I O.OY.) I I O.OY.J I I 0.0Y. I I I o.o;o I I 0 . 01.) I I I 14 . 3%1
I I I I I I I I
STIFFH£SS/TIGHTNESS I l I o I O I O I O I O I I l
I I 7.lr.1 I I 0.01.l I I O.Or.l I t 0.01.1 I I 0.01.1 I I 0 . 01/.1 I I I 7 . 1%1
-----------------------------------l----------l----------l----------
sysrn11c I l I 2 I 1
l----------l----------l----------l----------l-----------
I 1 I l I l I I ft
I t 7.lr.l I I l't.31.1 I t 7. 1%1 I I 7.lr.l I I 7.llO I I 7.lY.l I I I 28.61.1
I
loMOLE 80DY /GENERAL I 1 O I 1 1 I 1 I l I 3
7.UO ( 0.01.I I I 7. l r.1 t 7.liO I l 7,11.1 I I 7.lZI I I 21.47.1
I I
CHILLS I 1 O o O O I O I 1
7 . 1)0 I o.o:o I 0 . 0%1 I 0.0r.l I o.or. , I ( 0.01.1 I I 7.17.l
I I
SENSATION OF NAiMTH , GENERAL I O O a 1 1 I l I 1
o.o:o I 0.0)0 I o.o:o I 7. 17. l I 7.11.l I I 7.11.1 I I 7.1)0
I I
ILLNESS, NOS I O O 1 0 0 I O I l
o . o:o ( 0.0)0 I 7 . 1%1 I 0.0%1 I 0 . 0%1 I I a . o:o I I 7 . lr.1
I I
RESPIRATORY I o 2 0 0 0 I O I 2
o.o;o I 14.37.I I O. o:o I 0.07.t I 0.01.t I ( 0 . 01.1 I I lt+.3:0
I I
PHARYNGITIS I SORE THROAT I I O 1 a O o I O I 1
1 o.o;o c · 1.1:0 , 0.01.1 c 0.01.1 c o.o;o I , a.ox, I I 1 1.1x1
I I I
UPPER RESPIRATORY INFECT., HOS I o 2 O 0 0 I 0 I I 2
I I o.o:o I 14.3)0 I I 0 . 07.1 I O.OY.I I I 0.0%1 I I O. OXI I I I 14.3%1
-----------------------------------1----------l----------1----------l----------
PEASONS WITH Cot1PUIHTS I ll I 2 I l I 1
l----------1----------I----------I-----------
I 1 I 1 I I 5
I I 21.47.1 I I 14.lr.1 I I 7 . lr.1 I I 7. 17.1 I I 7.11.1 I I 7.11.1 I I I 35 . 7%1 0
0
"'""
..,.,
-
Table 2 (cont.)
PATIENT courr CLINICAL C0t1PLAINTS
RECOM8INAHT HEPATITIS 8 VACCIHE
LOT ICK446
ST\JOY 0789
TREATMENT
DOSE 20 11CG
I TOTAL VACCINEES ( 14 PATIENTS) - DOSE Z I

1----------------------------------------------------------------------------I
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------I
I O . I 1 I 2 I J I 4 I 5 I
WITH
ICOMPUINT$
••••••••••••••••••••••-••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••••••••••••••I••••••••••
-----------------------------------1----------1----------1----------•----------I----------I----------I----------I-----------
PERSCJIS WITH HO C011PLAINTS I 11 • 12 I 13 I 11 I 13 I 13 I I 9
I< 78.6X>. < es.no I I 92.97.) I I 92.97.1 I I 92.97.> I c 92.91.) I . I 1 6<t.l7.I
-----------------------------------1----------l----------l----------l----------l----------l----------l---------·I-----------
PEAsOHs WITH HO DATA I O I O I O I O I O I O I I 0
I I 0.07.1 I I 0.07.1 I C 0.07.1 I C 0.07.1 I I 0.07.1 I C o.or., I • I 0.07.I
0
-::,
....,
I\J
.E:
·-
Table 2 {cont.)
PATIENT CD~T CLINICAL COl1PLAIHTS
REC011BINANT HEPATITIS B VACCitlE
LOT I CK446
STUDY 078?
TREATNENT
DOSE : 20 t1CG
PATIEHT CLASS: PRE-DIALYSIS PATIENTS
I TOTAL VACCINEES ( 7 PATIENTS> - DOSE l I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I Nl.ltl8ER
CLINICAL
COtlPLAIHTS
1----------------------------------------------------------------------------I
I O I l I 2 I l I 4 I S I
WITH
ICOtlPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l•••••••••• l•••••••••• l••••••••••l•••••••••• l•••••••••• l•••••••••• I••••••••••
I I I I I I I I
REACTION, LOCAL I INJECT. SITE I I 1 I 1 I O I O I O I O I I 1
I « 14.37.1 I I 14.31.1 I I 0.07.1 I I 0 . 0%1 I I 0.0;:1 I I 0.07.l I I I 14 . lY.l
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
soREtlESS I 1 I o I o I o I o I o I I 1
I « 14 . 31.I I I 0.0;:1 I ( o.or.1 I ( o.or.1 I I 0.0;:1 I I o.07.1 I I 1 14.3%1
I I I I I I I I
STIFFHESS/TIGHMSS I l I 0 I 0 I O I o I 0 I I l
I « 14.31.1 I I o.or.1 I I o.O½I I ( o.0%1 I ( 0 . 0;:1 I I 0.07.J I I 1 14,3%1
I I I I I I I I
ECCHYMOSIS I o I 1 I O I o I o I o I I 1
I ( O.Oi:I I ( 14.3%1 I I O. O½l I ( O.OY.I I ( O.OY.I I « O. OY.I I I ( 14 . 3%1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l
srsTENIC I 2 I 1 I 1 I z I z I 1 I 1
-----------
2
I ( Z8.6i0 I l 14.3?.l I I 14.3½l I « 28.67.I I ( 28 . 61.l I ( 14.li:l I I 1 28.6Y.l
----------------
1 I
lollOLE BODY/GENERAL I l I O I 0 I 1 I l 0 l
( 14 . liO f ( 0.0%1 I I O.O½l I ( l<t.lY.l ( 14 , 37.1 ( 0 . 07.l I 14 . liO
I I I
CHILLS I 1 I O I O I 1 1 O 1
I 14.li:I I ( O.OY.l I I O. Oi:J I C 14.li:I ( 14.17.1 ( 0.07.I I 14.17.1
I I I
DIG£STIVE SYSTEtt I 1 I l I l I 2 2 1 2
I 14.31.J I C 14 . lY.I I I 14.31.1 I ( 28.6½1 « 28 . 67.1 ( 14.37.1 I 28.67.I
I I I
NAUSE A I 1 I 1 f l I Z 2 l 2
U.li:J I ( 14.37. 1 I ( 14.liO I ( 28.67.1 < 28.67.J ( 14.37.1 ( 28.6i:I
I I I
VOHITIHG I 1 I 1 I 1 I 1 1 1 1
I I 14 . l?.I I ( 14.3%1 I I 14.31.1 I I 14.37.l I 14.37.1 I 14.37.1 I 14 . 37.l
-----------------------------------1----------I----------I----------I----------I----------
PERSONS WITH COMPLAINTS I 3 f 2 I l I 2 I 2
I----------I----------I-----------
I 1 I I 3
. I « 42.91.1 I I 28.6i0 I I 14.37.1 I I 28.6½1 I I 28.61.1 I « 14.3%1 I I I 42.91.l
-----------------------------------1----------t----------
PERsONs WITH NO CONPUINTS I 4 I 5
l----------l----------l----------1
I 6 I 5 I s I
----------l----------l--
6 I I
·--------
4
I I 57.UO I ( 71.'t%1 I I 85. 7½1 I I ?l.41!1 .I I 71.4i0 I I 85. 77.J I I I 57 . lY.l 0
0
-...e
N
.. V1
Table 2 (cont.)
PATIENT COUNT CLINICAL COlff'LlIHTS
RECOM8IHAHT HEPo\TITJS 8 VlCCitlE
LOT ICK446
STUDY 0789
TREATMENT
DOSE 20 t1CG
I TOTAL VACCINE£$ f 7 PATIENTSI - DOSE 3 I

l----------------------------------------------------------------------------1
I OATS POST VACCINATION I HUl1BER
CLINICAL
CONPLAINTS
1----------------------------------------------------------------------------I
I O I 1 I Z I 3 I 4 I 5 I
WITH
ICOMPUINTS
..•••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••-•••••••••••l••••••••••I••••••••••
-----------------------------------1----------1----------1----------1----------1----------•----------1----------t-----------
PERSOtlS MITH NO DATA I o I o I o I o I o I o I I o
I ( 0.01.1 I l 0.01.1 I ( 0.07.1 I I 0.07.1 I I 0.07.1 I I 0.07.I I I I O.Or.l
0
0
""
IV
0-
--
Table 3
PAT IENT COlMT HAXl11UH TEHPERATURES
RECOl1B1NAHT HEPATITIS 6 VACCINE
LOT 1Cll446
STUDY : 0789
TREATHEHT
DOSE: 20 NCG
PATIENT CLASS: PRE-OULYSIS PATIEIITS

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATIOH I tM18ER
1---------------------------------------------------------------------------------------I
HAX TEMPERATURE
(DEG F , ORAL I
........................ , , I 2 I 3 I 4 I 5 I I
,
I
I HAW ITH
.......... .......... ,..........•.......... •.......... .......... .......... ....................
I O I l >< TEHP
,
I
,
NORMAL I 2 2 2 2 2 I 2 I 2
llt.37.J I 14.37.I t 14.3)0 I 14.37.I ( 14.lY.I I ( 14.3:f. l I I llt.l:f.l
I I
< 99 I 9 10 11 10 9 I 11 I 6
6lt.37.I ( 71.4:0 ( 78.67.1 I 71.4:f.l I 64.lY.I I I I
78.6:f.l I 42.97.1
I I
419 - 99. 9 I 2 1 l 1 l I 1 I 4
14.liO ( 7.lY.I I 7.17.1 I 7 . 17.1 I 21.47.1 I C 7.lXI I I 28,67.I
I I
101 - 101. 9 I o o o 1 o 1· o I 1
1. 07. 1 ( 0.07.) I 0.0XI I 7.17.1 C o.o;o I I 0.07.I I I 7.1)0
I I
102 - 102. 9 I 1 1 o o o I o I l
I f 7.UO I I 7.llO ( 0.07.1 I 0.07.1 c O.0Y.I I ( O.0Y.I I f 7.lY.I
------------------------l----------•----------1----------l----------
TENPERATURE TAKE N I 14 I l it I 14 I lit
l----------1----------1---------------------
I l it I 14 I I-----------
I 14
I noo.o;o I uoo.o::o I noo.o;o I noo.ox, I noo. or.1 I uoo.ox1 I I 1100 . or.1
------------------------1----------1----------1----------I----------I----------I----------I---------------------I-----------
TEt1PERATURE NOT TAKEN I O I O I O I O I O I 0 f I 0
I I D. 07.1 I I O. 07. I I I O. Di! I I I O. Ol! I I I O, 0)! I I l O, o;o I I I O. 0)0
0
0
'""
N
...a
.,
Table 3 (a::mt.)
PATIENT CDUtlT NAXlfflJ'I TEl1PEAAllJRE5
AEC0t18IHANT HEPATITIS B VACCIUE
LOT ICl(.446
Sl\JOY . 0789
TAEATNEHT
DOSE 20 t1CG
PATIENT CLASS PAE-DIALYSIS PATIENTS
I · TOTAL VACCINEES ( 14 PATIENTSI - DOSE 2 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUM6EA
NAX TENPEAATURE
I DEC F• ORAL I
l---------------------------------------------------------------------------------------1
I O • l I 2 I 3 • 4 • S I I I NAX~ITH
TENP
••••••••••••••••••••••-1••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••1••••••••••1••••••••••
NOllttAL I l l I 1 I ·1 1 1 I I l
• l 7.11.)
7.T/.l I I I 7.17.l I I 7.llO I 1.11.1 •I 1 7.liO I I I 7.11.)
I I I I I I
I I I I I I
< 99
I
I
11
I 84.61.) I
I
9
I 64.3)0 I
I
9
I 64.3)0 I
11
I 78.67.·) I
12
as. T/.) I
12
I
I 85. 71.)
I
'I 6
I 1 42.9"/.l
'19 - 99.9 I 0
0.07.I
I
I
2
I 14.JlO
I
I
3
I 21.47.l
'
I
I I
1
7 .17. I I
l
1.1z1
I•
I«
0
o.o;o
I
I
I
I
4
I 28.67.l
I I I I I
100 - 100.9 I 0 •• 2 I 1 I 1 0 0 I I 1
o.o:c1 • I 14.3lO I I 7 .17. I • I 7 .17.I ( o.o;o I• , 0.01.1 I I I 7 .17.1
102 - 102. 9 I 1 I o I o • o I o • l I I 2
I I 7. 77.1 I I o.oio I I o.o:c1 I I 0.01.1 • I 0.01.1 I I 7.llO I I I 14.llO
------------------------l----------l----------t----------1----------1----------1----------I---------------------I-----------
TENPERATUAE TAKEN I 13 I 14 I 14 • 14 I 14 • 14 I I 14
I I 92.9iO • 1100.oio • 1100.0tl I 1100.07.1 • U00.07.l • U00.07.1 • I 1100.0;0
------------------------1----------1----------l----------•----------•----------l----------•---------------------I-----------
TENPERATUIE NOT TAKEN I 1 I o I o I o I o I o I I a
I I 7.17.) I I 0.01.) I I 0.01.) I I 0.07.I I( 0.0)0 I( O.OiO I I I O.OiO
0
0
--.f
IV
a,
•
Table 3 (cont.)
PATIENT COUNT NAXItlU'I TEffllEAAT\JlES
AECOttBINANT HEPATITIS 8 VACCINE
LOT I CK446
STUDY 0789
TRUTNENT
DOSE 20 NCG
PATIENT CLASS PAE-DIALYSIS PATIENTS
I TOTAL VACCIN£f.S C 7 PATIENTS I ._ DOSE 3 I

1• ------------------------------------------------------------.
--------------------------1I NJMBER
l---------------------------------------------------------------------------------------1
NAX TEHPERATURE
I DEG F, M ALI I O I l I 2 I 3 I 4
, I 5 I I
WITH
• NAX -TENP
......................................................... .............................. ..........•..........•..........
I
,
I
NOA11Al • l 2• 21 2 2 Z\ 1
C 14.31.1 I 28.61.1 I C 28.61.1 I C 28 . 6:t.t C 28 . 61.1 ( 28.6)(1 • C 14 . 31.1
< 99 • 1 4 II 4 I• 3 2 4 I• z
I 42.91.I C 57.11.1 I ( $7.llO I C 42.97.1 C 28 . 6%1 C 57. 1)( 1 I C 211 . 6:iO
I I I
99 - 99. 9 • 3 o I O I l l l I 2
I 42 . 9"/.I C 0.0%1 I C O.0Y.I ( C 14.3% 1 C 14.3% 1 C l4 . 3Y.I I f 211.6%1
I • I
no - 100 . 9 I 0 1 I l I O l 0 I 0
o.o::o C 14 . 3%1 I C 14.31.l I C 0.o:o I 14 . lY.I C 0.07.1 I C O.OiO
I I I
101 - 101 . 9 I o o I o I 1 o o I l
0.01.1 C 0.01.) I ( 0.01.1 I C 14.3Y.) I o.o:o ( O.0l!I I C 14.])()
I I I
104 - 104 . 9 I o c, I o I o 1 I o I 1
I ( 0.OY. I I C 0.0)0 I I 0.01.1 I I 0.0)() I 14.]XI I ( 0.0:i() I I I lit . ])()
------------------------•----------•----------l----------t----------•----------l----------1---------------------1-----------
TENPHATURE TAKEN I 7 I 7 I 7 I 7 • 7 • 7 I I 7
• noo . o;o • 1100.o;o I 1100.0;0 I 1100.0::0 I uoo.o;o I noo.01.1 I I 1100.01.,
------------------------ •----------1----------•----------l----------•----------1----------1---------------------
TEHPEAATUlE NOT TAKEN • 0 I I I D I O I O I O I •I-----------
D
• ( 0.0)() I I 0. 11.1 I ( 0.01.I • ( 0.01.) I I 0.01. , I I a.au I I ( D.D1.1
0
0
-'8
N
-0
•
Table 4
PATIENT COUNT CLINICAL COHPLAttrrs
REC01'18IHANT HEPATITIS 8 VACCIIIE
LOT ICK446
STUDY 0789
TREATMENT
DOSE 40 t1CG
I TOTAL VACCINEES I 15 PATIENTS I - DOSE l I

t----------------------------------------------------------------------------1
I DAYS POST VACCIIIATIOH I NlltlBER
CLINICAL
C011PLAINTS
1----------------------------------------------------------------------------I
I O I 1 I 2 I '3 I 4 I 5 I WITH
ICOttPLAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION, LOCAL IIHJECT. SITE I I O I 2 I O I O I O I O I I Z
I I o.0ll I I 1'3.3%1 I I 0.0%1 I I 0.0%1 I I 0.0%1 I < 0.0%1 I I I 13.31/.1
-----------------------------------1----------t----------l----------l----------l----------l----------1----------1-----------
soRENEss I O I t I O I O I O I O I I Z
I I O.OY.J I ( 1'3.1%1 I C 0.0%1 I I 0.0%1 I I 0,01.I I ( 0.0%) I I I 13.]%1
-----------------------------------t----------l----------l----------l----------l----------l----------l----------l-----------
sysu111c I 0 I 1 I 1 I l I 0 I 0 I I l
I I o.07.l I c 6.77.1 I c 6.7%1 I I 6.7%1 I I 0.0%1 I I o.or.1 I I I 6.7%1
-------------------------------------------
DIGESTIVE SYSTEM I 0 I l
'I 0 0
II 0
II 0 I I l
0.07.1 I c 6.77.1 I c 0.0%1 I o.ox1 I I 0.0%1 I I 0.0%1 I I I 6.7%>
I I I I I I
NAUSEA I O I l I O O I o I o I I l
O.OY.I II 6.77.) II O.OY.I I O.OXI II 0.07.) II o.o;o I II 6.7½)
I I I I I I
PSYCHIATIUC/BEHAVIORAL I O I O I l 1 I O I O I I . l
o.o;o I 1 1.01.1 I c 6.7%1 1 ,.r1.1 I , o.o:o I I o.ox1 I I I t. .n,
I I I I I
DEPRESSION I 0 I O I l l I 0 I 0 I I l
I ( 0.07.1 I I 0.0%) I I 6. 7%1 I 6. 7%1 I ( 0.07.) I ( O.OX) I I I 6. 7%1
-----------------------------------1----------l----------1----------I----------I----------I----------I----------I-----------
PERSONS WITH CONPUINTS I O I J I 1 I 1 I O I O I I 3
I I D.OY.l I f 20.0%1 I I 6.7%1 I I 6.7%1 I I 0.07.) I I 0.01.1 I I I Z0.0%1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PEIISON!I WITH NO COt1PLAINTS I 15 I 12 I 14 I 14 I 15 I 15 I I 12
I 1100.01.1 I , eo.or., t 1 93.31.J I 1 91.11.1 t 1100.ox, I ,100.ox1 I I I eo.01.1
-----------------------------------1----------1----------l----------1----------I----------I----------I----------I-----------
PEIISDNS WITH NO DATA I O I o I o I O I O I o I I o
I I 0.0%1 I I 0.0%) I I 0.0%) I I 0.0%) I I 0.0%1 I I 0.0%) I I I 0.01.)
0
0
"""
uf
0
Table 4 (cont.)
PATIENT COUNT CLlNICAl COMPLAINTS
RECot1BIHANT HEPATITIS 8 YACCUlE
LOT •cK446
STUDY 0789
TREATM£ITT
DOSE 40 NCG
PATIENT CLASS: PRE-DIALYSIS PATIEITTS
I TOTAL VACCINEES ( 15 PATIENTS I - DOSE Z •

•----------------------------------------------------------------------------1
I DAYS POST YACCIHATIOH • llUl18ER
CLINICAL
COflPLAINTS l----------------------------------------------------------------------------1
• 0 I l • Z • 3 • 4 • 5 I WITH
•CotlPLAIHTS
·································••l••····························•·l••····························••l••·······•·R·•·······
• • I I 1 I I I .
REACTIOH, LOCAL UNJECT. SITE> I l I O • o I O I o I O I • 1
I I "6,77.1 I I 0.07.I I I 0.0:t.l • I O.OXI I I 0.07.1 I I o.OZI I • I 6.7%1
-----------------------------------•----------•----------1----------1----------1----------•----------I----------I-----------
SORENESS I 1 I o I o I o • o I o I • 1
I I 6 • 7%) • I O• O:t.) I I O. O:t. I I I O. 0% I I I O. 0% I • · I O. oz I • I ( 6 . 7:t. I
-----------------------------------1----------l----------•----------t----------l----------•----------l----------•-----------
srsTENIC I O I 1 I 1 I O • 0 • 1 I I 2
I( 0.0%1 I( 6.7%1 I I 6.7%1 I I 0,0%1 I I O.OZI I I 6.7ZI I •( 13.3%1
------------------------------------
RESPIRATORY 'I
• (
O
0. 0% I (
O
0. 0% I (
l
6. 7:t. I
I
I I
O
O. 0% I I
O
O. 07. I I
O
O. 07.1 I
1
6. 7% I
I I
UPPER RESPIRATORY INFECT., NOS • 0 0 1 I O O O 1
• I O. 07. I I O. 07. I ( 6. 7:t. I I < 0. 0% I ( 0. 0% I C O. 0% I C 6 . 7% I
I I
DIGESTIVE SYSTEN I O O O I O O l 1
• ( 0. 0% I ( 0 • 07. I I O• 0% I I ( 0 • 0% I C O. 0% I I 6 • 7:t. I I 6 • 7% I
NAUSEA
•• 0 0 0
II O O 1 1
• I O.OY.I I 0.0:t.l I O.OiO. I O.OY.I I 0.0:t.l C 6.7i0 I 6.7%1
PS'YCHIATIIIC/BEHAVIORAl •I O l O •I O O O l
• I 0,0%1 C 6.T/.1 C 0.0%1 I I O.O:t.l C 0.0%1 C 0.07.1 I 6. 7%1
• I
DEPRESSION I O 1 0 • 0 0 0 l
I c o. 0:1.1 • , , • 7% 1 c o. ox I I , o. o:o I c o. ox 1 • 1 o. o:o , 6. 1;n
-----------------------------------•----------•----------•----------1----------1----------•----------•----------•---·-------
PERSOHS WITH Cot1PLA1KTS I 1 I 1 I 1 I o I O • 1 • • 2
• , 6.77.1 • , 6.77.1 • , 6.1:t.1 • 1 0.0:t.1 • 1 0.0:t.1 • 1 6.77.1 I I , 13.lXI
-----------------------------------1----------•----------•----------1----------I----------I----------I----------I-----------
PERSOHS wrm HO Cotfl'UINTS • 14 I 14 I 14 I 15 I 15 I 14 I I ll
I ( 93.3:t.l I ( 93.3:t.l I I 93.37.1. 1100.0%1. U00.07.1. I 93.37.1 I I I 86.7%1
-- ·---- ·---------------------------l----------•----------l----------•----------l----------1----------1----------1-----------
PERSONS WlTff HO DATA I O • O • o • 0 I 0 • o I • 0
I I 0.0%1 • c 0.0%1 I I 0.0:1.1 I I o.or.1 I I 0.0:t.1 I c o.or.1 • • c o.oz1 0
0
--.!
- -
1.,,1
Table 4 (cont.)
PATIENT COUNT CUHICAL COtlPLAlllTS
REC0t18IHAHT HEPATITIS B VACCillE
LOT ICK446
STUDY 0789
TRUTMEHT
DOSE 40 MCG
PATIEHT CUSS: l'RE-DULYSlS PATIENTS
I TOTAL VACCINE ES ( 7 PATIENTS I - DOSE 3 I

l----------------------------------------------------------------------------1
I DAYS POST VACCmATION I HU1BEI!
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------I
I O I 1 I ' 2 I 3 1 4 I S •
WITH
!COMPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••I•••••~••••
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
sysnt1It I o I o I o I o I o I· 1 I I 1
I I 0.0)0 I I o.o:o I I 0.07.I I I G.07.I I I 0.0:1.1 I I 14.3:~, I I I 14.31/.I
---------------
1
------------------------------------------
I I
~OLE BODY/GENERAL I 0 0 0 I 0 D I 1 I l
0.07.1 ( 0.07.I I G.07.l I I 0.07.I I 0.07.1 I I 14.37.1 I I 14.37.l
I I I
FATIGUE/lolEAktlESS I O O O I O O I 1 I l
o.o:o l 0.07.I l 0.01.l I l 0.07.1 I 0.01.1 I I 14.3%1 I I 14.JY.I
I I I
DIGESTIVE SYSTEH I O O O I O O I 1 I l
0.07.I C 0.07.1 C o.o:o I I 0.0)0 I 0.01.1 I I 14.37.1 I I 14.37.I
I I I
HAUSEA I o o o I o • t 1 I 1
0.07.) I 0.07.1 I 0.0¼1 I I O.O¼I I 0.07.I I I 14.3%1 I r 14.31/.I
I -1 I
ABO<l1INAL TENDERNESS I 0 0 0 I 0 0 I l I 1
I I 0.0)0 I 0.0)0 ( 0.07.I I ( 0.0)0 I 0.0)(1 I I 14.37.1 I I 14.37.1
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
P£1!SONS WITH COtlPLAINTS I 0 I O I O I 0 I O I 1 I I 1
I I O.OY.I I I O.OY.I I I o.OY.l I I 0.01/.I I I 0.07.l I t 14.31/.1 I I l 14.Jr.l
-----------------------------------1----------l----------1----------1----------I----------I----------I----------I-----------
PERSONS WITH NO COHPU.INTS I 6 I 7 I 7 I 7 I 7 I 6 I I 6
I 1100.oz1 I 1100.01.1 I 1100.01/.1 • 1100.oz> I 1100.01.1 I r es.1x1 I I I aS.71/.J
-----------------------------------l----------l----------l----------1----------I----------I----------I----------I-----------
PEASON9 WITH NO DATA I o I a I o I o I e I o I I o
I r o.OY.I I I o.07.l I I 0.01/.l I l D.07.l I c o.o¼t I t o.OY.I I I I a.or.I
0
0
.....
"'
, "'
Table 5
PATJEHT COUHT 11.lXItt.m TEnPERATURES
RECOH8IRAHT HEPATITIS 8 VACCIIIE
LOT ICK446
S1\JDY 0789
TREATHEHT
DOSE 40 t1CG
I · TOTAL VACCINEES ( 15 PATIENTSJ - DOSE 1 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUffllER
HAX TEMPERATURE
(DEG F, OIUU
1---------------------------------------------------------------------------------------I
I O I 1 I Z I 3 I ft I 5 I I
WITH
I tlAX TEl1P
••••••••••••••••••••••••1••••••1111•• •••••••••• •••••••••• ••••••••••!•••••••••• ••••••••••l••••••••••I•••••••••• ••••••••••
I I
HOl!HAl I 1 l l l I 1 1 I 1
7 .17.) I 7 .17.) I 6. Tl.) I 6. 7i0 I I t.. 77.1 I ·7 .17.1 I I . 6. 7i0
I I
< 99 I 10 11 12 12 I 12 11 I a
71.47.1 C 78.6)0 I 80. o:o ( eo.o:o I f 80 .0)0 I 78.6Y.I I I 53. 3i0
I I
99 - 99. 9 I 2 l O 2 I 2 l f 4
14.3Y.I ( 7.liO I 0.07.1 I 13.3Y.I I I 13.lY.J I 7.lY.J I I 26. 71.1
I I
101 - 101. 9 I l 1 2 o I o 1 I 2
I I 7.17.1 I 7.17.1 I 13.37.1 I 0.07.) I I o.o;o I 7.lY.I I I I ll.3%1
------------------------l----------l----------1----------1----------1----------I----------I---------------------I-----------
TEttPERATIJRE TAKEN I 14 I 14 I 1!. I 1!. I 15 I 14 I I 15
I I 93.lY.J I I 93.37.) I (1110.07.) I 1100.07.1 I 1100.0;0 I I 93.37.J I I 1100.0iO
------------------------l----------l----------l----------1----------1----------1----------I---------------------I-----------
TENPERA~E NOT TAKEN I l I 1 I O I O I O I 1 I I O
I I 6.7,0 I I 6.77.1 I I o.o;o I I 0.07.) I I 0.07.) I ( 6.77.1 I I I O.OiO
0
...,::,
""
""
.,
Table 5 (cont. )
PATIENT COUNT HAXIHUt TEHPERA~ES
LOT ICK446
STUDY 0789
TRUTHENT
DOS£ 40 t1CG
I TOTAL VACCINEES I 15 PATIENTSI - DOSE 2 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATIOH I »Jt1BER
MAX TEtlPERAT\JRE
CDEG f, ORAll
l---------------------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I S I •
WITH
I 111~ TEHP
······················••1••······••1••·················••1••······••1••······••1••·················••1••······••1••········
I I
NOl!t1ll I I 1 1 1 l I 1 I I l
7.1?.I I 6. Tl.I I 6. 7:1.1 I 6."7:1.1 I 6.77.1 I I 6.7?.) • I I 6. 7XI
I
< 99 I 10 11 10 13 14 I 14 I I 8
71.4?.I I 7:J.3?.I I 66.77.> I 86.77.1 C 93.37.1 I I 93.liO I I I 53.lY.l
I I I
'99 - 99. 9 I l 2 Z l o I o • I 4
21.4?.I I u.:s:o I n.:s:o I 6.77.) C 0.07.) I I I
0.07.1 I I 26.7i0
• I I
uo - 100. 9 I o o 2 o o I o I I I
a.ox, I 0.0)0 I 13.liO I o.o:o C 0.07.). C D.07.) I I I 6.7)()
I I I
101 - 101.9 I o l a a o I o I I 1
I C O.Oi!I I I 6.7X) I I o.o;o I I o.o:o C 0.0XI I I D. 07.) • I I 6.7iO
------------------------l----------l----------l----------l----------t----------l----------l---------------------•-----------
n11Pu1TURE TAKEN I 14 I 1s I 15 I 1s I 1s I 1s I I 15
• c 93.3l0 I 1100.0i!I I 1100.0i!I I 1100.0?.I I 1100.07.1 I 1100.07.1 I I 1100.0iO
------------------------l----------l----------l----------t----------l----------l----------1---------------------1-----------
TEHPIERATURE HOT TAKEN I 1 I O I D I O I O I O I I 0
I c 6. r1.1 I I o.ox1 I , o.o:u I , o.o:o I , o.oio I c 0.01.1 I • c o.o;o
0
c:,
-.,
w
.c,
•
Table 5 (cont.)
PATIENT COUNT Hl XItlJN TEHPERATUlES
RECOtt8IHAHT HEPATITIS 8 VACCINE
lOT ICl<446
STUOY 0789
TRU THENT
DOSE 40 t1CG
I TOTAL VACCINE ES I 7 PATIENTS) - DOSE 3 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I tlUl19ER
HAX TEHPERATURE
(D[G F , MALI
1---------------------------------------------------------------------------------------I
I O I 1 I 2 I 3 I 4 I 5 I I
WITH
I H,t.X TENP
•--••••••••••••••••••••l••••-••••I••••••••••
I
•••••••••• ••••••••••1
I
••••••••••1
I
••••••••••1••••••••••1 •••••••••• ••••••••••
HORN.U Ill 1 l 1 1 11 1 l
16.7Y.I I C 14.37.1 ( 14.37.1 C l ft . 37.I I I ( 14 . 37.)
I 1 4.3)0 I 14,3;0
I I I
<99 I J I 5 s 6 I 4 I 4 z
I S0.07.J I I 71 . 4iO I 71.47.J I 85 . 77.) I I 57.UO I I 57.17.1 I t8.6r.J
I I I
99 - 99.9 I 2 I 1 o o I o I l 1
I U.37.1 I I 14.li!J I O.Oi!I I 0 , 07.1 I I 0.0lO I I l4.3r.l I 14.3:1.1
I I I
100 - 1 00.9 I o I o o o I 2 I o 1
o.o:o I ( 0 . 0iO ( 0.07.1 I 0.07.) I I 28.6)0 I ( 0.07.1 I 14 . 3)0
I I I
101 - 101.9 I o I o 1 o I o I 1 2
I I 0.0lO I I 0.0i!I C 14 . 3:-!I I 0 . 07.1 I I 0.07.I I I 14 . 37.1 I 28 . 6iO
------------------------1----------t----------1----------t----------
TEHPERATIJRE TA~EH I 6 I 7 I 7 I 7
t----------l----------1---------------------1-----------
I 7 I 7 I I 7
I , as.r.< 1 I 11110 . oY. 1 I noo.oz, I noo . o:o I 1100.oz1 I 1100 . oY.1 I I 1100 . 0;0
------------------------l----------1----------1
n11PERATURE HOT TAKEN I 1 I o I
----------l----------
o I o
t----------1----------1
I o I o I
---------------------l-----------
I o
I < 14.37.J I I 0.0i!J I l 0.Oi!I I t 0.07.) I I 0.07.) I I 0.07.1 I I I 0.07.1
0
0
"
~
u,
•
Table 6
PLAStlA-DERIYEO HEPATITIS B YACCIIIE
LOT WZ449H
STUDY 0789
TREATHENT
DOSE 40 t1CG
I TOTAL YAttmEES ( 16 PATIENTS) - DOSE l I

l----------------------------------------------------------------------------1
I DAYS POST VACCIIIATIOH I 1-M18ER
CLINICAL
COtlPUINTS
1----------------------------------------------------------------------------I
I 0 I 1 I 2 I 3 I it I 5 I ~ITH
ICOtll'LAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I•••••~••••
I I I I I I I I
REACTION, LOCAL CIHJECT. SITEI I 1 I 0 I 0 I 0 I 0 I 0 I I 1
I 1 6.11.1 I ., o.o;o I I o.or.1 I I o.o;o I 1 0.0:1.1 I 1 0.0:1.1 I I 1 6.3Y.J
-----------------------------------l----------t----------l----------l----------l----------l----------l----------l-----------
s011ENEss I 1 I O I O I O I O I O I I l
I r 6.3l0 I I o.o:o I I o.o:o I I O.OY.I I I 0.0:1.1 I ·1 o.o:o I I I 6.3Y.I
----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sysnHit I . l I l I O I O I O I O I I l
I I 6.3Y.I I I 6.3Y.I I I O.OY.I I « O.OY.I I I O.OY.I I I O.OY.I I I I 6.31.1
----------------------------------------
1 I I I
lol!OLE BOOY/GEHERAL I l I 1 I O . I O I O I O I I l
I I 6.31.1 I I 0 . 01.1 I I o.OY.I I I 0.01.1 I I O.OY.I I
6.3Y.I I I 6.3Y.I
I I I I I I I
SENSATION OF WARHTH, GENERAL I 1 I l I 0 I O I 0 I .D I I l
I I 6.31.I I I 6.3Y.I I I O.OY.I I I O.OY.I I f O.OY.I I I O.OY.I I I I 6.31.1
-----------------------------------1----------l----------l----------l----------1----------I----------I----------I-----------
PERSOHS WITH COliPLAIHTS I 2 I 1 I o I O I o I O I I 2
I I 12.SY.I I I 6.31.1 I I o.o;o I I 0.0Y.I I I O.OY.I I I O.OY.I I I I · 12.SY.I
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l---·-------
PERSONS WITH HO COHPUIHT!I I lit I 15 I 16 I 16 I 16 I U, I I 14
I 1 87.SY.t I < n.e:o I 1100.or.1 I 1100.oz, I uoo.o;o I uoo.o;o I I 1 87.SY.J
-----------------------------------1----------l----------l----------l----------l----------l----------1----------I-----------
PERSONS WITH HO DATA I O I o I O I O I O I O I I o
I I O.OY.I I < 0.01.1 I I O.OY.I I I O.OY.I I I 0.0%1 I I O.OY.I I I I 0.01.I
0
...,
0
\,-1
0-
•
Table 6 (cont. )
PATIENT COUIIT CLINICAL COl1PLAltlTS
PlAStfA-DERIVED HEPATITIS B VACCIIIE
LOT 112449H
STUDY 0789
TREATMENT
DOSE 40 HCG
I TOTAL VACCitlEES I 16 PATIENTS I - DOSE Z I

1----------------------------------------------------------------------------I
I DAYS POST VACCIHATIOM I NUN!IER
CLINICAL 1----------------------------------------------------------------------------I . MITH
COHPUIHTS I 0 • 1 I Z I 3 I 4 I 5 I ltOtlPLAIHTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION, LOCAL UHJECT. SITE I I l I O I O I o I o I o I I 1
I I 6.3?.I I I O.OY.I I I 0.07.1 I I O.OXI I I D.0%1 I t 0.0%) I I t 6.3r.l
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PAIH I l I o I o I o I o I o I I 1
I I 6.3?.I I I 0.07.I I I 0.07.1 I t 0.0%1 I I D.0%1 I I 0.07.1 I I I 6.3r.l
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
svsTEttIC I O I l I O I 1 I O I O I I 2
I t O.OY.I I I 6.37.1 I I 0.07.1 I I 6 . 3XI I I o.0%1 I I 0.01/.1 I I __________
,..t 12.sr.1 _
I
WHOLE BODY/GENUAL I O I l I O I O I O I o I I l
t 0.0?.1 I 1 6.3iO I I o.o:o II o.o;o I t o.o:o II o.ox1 I 1 6.Jr.1
I I I I I I
FATIGUE/WEAKNESS I O I l I o I O I O I o I 1
0,01.1 I I 6.37.1 I I 0.0)!) II 0.07.) I t o.o:o II o.o;o I I 6.JX)
I I I I I I
HUSCULOSKELETAL I O I O I O I 1 I O I II I 1
o.o:o I I o.ox1 I t o.on I, 6.3iO I 1 0.0?.1 I, o.ox1 I t 6.:s:o
I I I I I I
ARTIIRALGU I OTHER I I O I O I O I 1 I O I O I l
I I 0.07.1 I I 0.07.I I I 0.07.I I I I 0,0%1 I I o.o:o I
6.3i0 I' I 6.37.1
----------- · -----------------------1----------1----------I----------I----------I----------I----------I----------
PERsoHs WITH c0t1PLAINTS I 1 I 1 I o I 1 I o I o I
-----------
z
I I 6.3%) I I 6.37.l I I 0.07.l I I 6.37.1 I I a.ox, I ( 0.0?.I I I 12.5?.I
-----------------------------------1----------l----------l----------l----------l----------l----------1----------
PERSONS WITH MO CONPUIHTS I 15 I 15 I 16 I 15 I 16 I 16 I I
-----------
14
I I 93.8)0 I I 93.8%) I 1100.07.1 I ( 93.87.1 I 1100.0?.l I 1100.07.1 I I I 157.51/.1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
PERSoHs wnH HO DATA I o I o I o I o I 11 I o I I o
I I 0.0;1,I I I o.o;o I ( 0.01.1 I ( 0.0;l,I I I 0.0?.I I t 0.0)0 I I I O.OXI
0
...,
c::,
__.., ...,
v'
Table 6 (cont.)
PAlIENT COUNT CLINICAL COMPLAINTS
PLASMA-DERIVED HEPATITIS 8 VACCINE ·
LOT 1~'+4'1H
STUOY 0789
TREATI1ENT
DOSE 40 HCC
I TOTAL VACCIHEES I 6 PATlENTSI - DOSE 3 I

l----------------------------------------------------------------------------1
I DAYS POST VACCIHATIOtl I HUl18ER
CLINICAL
CotlPLAINTS
l----------------------------------------------------------------------------1
I 0 I l I 2 I l I 4 I 5 I WITH
ICOMPLAINTS
•••••••••••••••••••••••••••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
I I I I I I I I
REACTION. LOCAL IINJECT. SITE I I l I O I O I O I o I o I I l
I ( lf,,7)O I C o.o;o I ( o.o:o I ( 0,07.) I. ( 0,07.) I I o.o:o I I I 16.77.1
-----------------------------------1----------l----------1----------I----------I----------I----------I----------I-----------
SORENESS I l I O I O I O I O I II I I l
I c 16.77.1 I c o.07.1 I c 0,07.1 I 1 0.07.1 I c 0,07.1 I 1 0.07.1 I I 1 16.77.1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
svsTEHIC I l I l I 1 I l I O I O I I l
I C 16. 77. I I ( 16. 7X I I < 16. 7i0 I f 16. 77. I I C· O. 07.1 I I o. o:o I I I u,. 77. J
I
WHOLE BODY /GENERAL I O O O l I O O I l
o.o:o C o.o;o I D.07.I C 16. 77.1 I I 0.07.1 I 0.07.1 I I 16. 77.1
I I
FATJGUE/MEAKNESS I 0 0 O l I 0 0 I l
0.07.1 C 0.07.1 I 0.07.I C 16.77.1 I C 0.07.1 ( 0.0%1 I I 16. 77.1
I I
DIGESTIVE SYSTEH I l l l 0 I 0 0 I 1
16.JY.I ( 16.7ll I 16.7%1 I 0.07.I 11 0.07.I ( 0.0%1 I I 16.77.1
I I
NAUSEA I l 1 l 0 I 0 0 I l
16. 7)0 C 16. n I ( 16. 7Y. I I 0. 07. I I ( 0. 07. I C O. 0% I I I 16. 77. I
I I
VOMITING I O l 1 O I O O I 1
o.o:o , u.1;:, c 16 . 77.1 1 o.o;o I I o.ox, c o.ox1 I 1 16.77.1
I I I
LOOSE STOOL I O D l O I O I O I I 1
1 1 o.o:o 1 1 o.o;o c 16.?Y.1 c o.oY.1 1c o.oY.1 I I o.o::o t I , 16 . 1x1
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
PERs01is WITH c0t1Pu1trrs I 2 I 1 I 1 I 1 I o I o I I z
I I 33.3%1 I c 16.77.1 I I 16.71/.1 I c 16.77.1 I I o.07.1 I c 0.117.1 I I 1 33.3%1
-----------------------------------1----------I----------l----------l----------l----------1----------1----------1-··---------
PERSONS WITH NO COflPLAINTS I 4 I 5 I S I 5 I 6 I 6 I I <+
I I 66.7X> I I 83.31/.l I I 83.3½1 I c 83.37.1 I 1100.0:0 I 1100.07.1 I I 1 66.77.1
-----------------------------------1----------l----------1----------l----------l----------l--·-------l----------l-----------
PERsOHs WITH NO DATA I O I O I O I O I O I D I I 0
I I 0,0%1 I I 0.07.1 I C O.O½l I I 0.0%1 I I O.0Y.I I I 0.0%) I I I o.O½I 0
0
"""
--
OD
Table 7
PATIENT COUHT MAXlt1U11 TEMPERATURES
PUSttA-DERIVED HEPATITIS 8 VACCIIIE
LOT l :.'.44911
STUDY 0789
TRE ATt1£HT
DOSE 40 MCG

1---------------------------------------------------------------------------------------I
I DAYS POST VACCIIIATIOtl I NlJ18ER
MAX TEMPERATU!IE
IDEG F, ORALI
1
I
---------------------------------------------------------------------------------------I
O I 1 I 2 I 3 I 4 I 5 I I
MITH
I MAX TEIIP
•••••••••••••••~••••••••!•••••••••• •••••••••• •••••••••• ••••••••••! •••••••••• •••••••••• ••••••••••••••••••••• ••~•••••••
I I
NORMAL I l l 1 1 I l 1 1
6.7i0 I 6,T/.l I 6.77.l I 6.7i0 I I 6.77.l I 6.7i0 r 6.7i0
I
< 99 I 12 12 13 11 I 11 12 10
ao.0:1.1 I 80 . 0Z l I 86.77.l I 7l.3Zl I I 73.3%) I eo.o;;n I 66 . 7?.l
I
99 - 99. 9 I l 2 1 l I 3 t l
6.7%1 ( 13.3%1 I 6.7,0 I 20.0Zl If 20.DZl f 13.liO f 20,0Z)
I
104 - 104 , 9 I l O O O I O O l
I 1 6. n> 1 o.or.1 1 o.or.1 I I o.o:o I I o. or., c o.or.1 1 6. n,
------------------------1----------1----------I----------I----------I----------I----------I-----------
TEttPERATURE TAKEN I 15 I 15 I 15 I 15 I 15 I 15 I
----------1-----------
I 15
I I 93.SY.I I f 93,8i0 I I 93.8i0 I I 93.8Xl I I 93.BXI I I 93.BX) I I 1· 93.8X>
------------------------1----------1----------l----------l----------l----------l----------
TEMPER ATURE NOT TAKEN I l I 1 I l I l I 1 f l
l---------------------l-----------
I I 1
I I 6,37.I I I 6 . lY.I I I 6.3?. l I I 6.3%1 I I 6.37.l I I 6.lXI I I I 6.lXI
0
0
....i
""-0
...
Table 7 (cont.)
PATIENT COUNT MAXI,.._, TEMPERATURES
PLASMA-DERIVED HEPATITIS B VACCINE
LDT IZ44911
STUDY 0789
TREATMENT
DOSE 40 11CG
PATIENT CLASS: rRE-DIALYSIS PATIENTS
I TOTAL VACCIIIEES I U, PATIENTS I • DOSE 2 I

1---------------------------------------------------------------------------------------l
I DAYS POST VACCitlATION I lrutmER
MAX TEMPERAT""E
I DEG F, OIU.L I
l---------------------------------------------------------------------------------------1
I O I l I 2 I 3 l It I 5 I I I
WITH
MAX TEMP
••••••••w••••••~••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••••••••••I••-•••••••
I I I I I I I I
NORMAL I 2 I 2 I 2 l 2 I 2 I 2 I I 2
I I 13,37.1 I« 13.3%1 I« 13.37.1 I« 13.3%1 If 13.37.1 I I 13.37.1 I I I 12.5%1
I I I I I I I I
< 99 I 11 I 12 I u I u I 12 I 12 I l u
I t 73.37.1 I l 80.0;0 I t 86.7XI I t 86.nl I c ea.ox, I 1 80.07.1 I I f . 68.81/.l
I I I I I I I I
99 - 99. 9 I 2 I 1 I o I o. I 1 I 1 I I 3
I I U. 3% I I c 6. n I I c o. 0% J I I 11. o:o I « 6. 7% I l I 6. 77. l I l « 18. 87. l
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEttPERATURE TAKEN I 15 I 15 I 15 I 15 I 15 I 15 I I H,
I I 93 . 8%) I ( 93.8%) I I 93.8%) I I 93.e:o I ( 93.8%) l I 93.87.) I I 1100.01/.I
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEMPERA T\JRE NOT TAKEN I 1 I 1 I 1 I 1 I l I I I I 0
I c 6.3%) I l 6.3%1 I I 6,37.1 I I 6.37.1 I c 6.1;0 I I 6.37.l I I t · o.o;o
0
0
......
C
0
Table 7 (cont.)
PATIEHT COUNT t1AXIM\Jt'I TEMPERATURES
PUSt1A-D£RIVED HEPATITIS B VACCIIIE
LOT 1244911
STUDY 0789
TPEATt1ENT
DOSE 40 tlCG
PATIEHT CLASS: rR£-DIALYSIS PATIENTS
I TOTAL VACCIUEES I 6 PATIEUTS l - DOSE 3 I

1---------------------------------------------------------------------------------------t
I DAYS POST VACCINATJOU I t1Ut113ER
tt AX TEMPERATURE
I DES F, ORAL l
1---------------------------------------------------------------------------------------I
I O I l I Z I J I 4 I 5 I •
~ITH
I MAX TEMP
•••••••••••••••••••••••• l••••••••••••••••••••• ••••••••••••••••••••••••••••••••• l•••••••••• l•••••••~•• ••••••••••• I••••••••••
I I
NOOtlAL I 1 1 1 l l 1 I I l
l6.7l!l I 11>.7;0 I 16.77.l I 16.7i0 ( 16.?Y.I I 16.7%1 I I I 16.71/.1
I I
< 99 I 4 4 4 ti s s I I 4
66.7i0 I 66.T/.I ( 66.7:0 I 66.7i0 l 83.3i0 I 83.37.l t I I 66,77.1
I I
99. - 99, 9 • 1 0 D 1 0 0 • • 0
16.7l!I I o.o;o I O.OZI I 16.77.1 I o . o;o I 0.01.1 I I I 0.0¼1
I I
100 - 100. 9 I o l o o o o I I o
0 , 07.1 l 16 . 77.l I O.OiO C 0.07.l ( o.o:o I 0.07.1 I • l O.O¼l
I •
lOZ - lOZ. 9 I O O l D O O I • 1
• I 0.01.l l O.O¼l I 16 . 7)!) ( 0.01.) ( 0.01.I • ( o.o;o I • I 16. 7X)
------------------------•----------•----------t----------l----------l----------l----------l---------------------l-----------
TEt1PERATUl!E TAKEN I 6 I 6 I 6 I I, I 6 I 6 l I 6
I 1100.01.1 I l l 00.01.l I 1100.oz1 I 1100 . 0¼l I 1100.01.1 I llOO.OZl I I 1100.01.1
------------------------l----------
TEt1PERATURE NOT TAKEN I O
l----------t----------l----------t----------t----------l---------------------l
• 0 I O I O I O • 0 I I
-----------
0
I I o . o:o I I O.OZI I I 0.07.J I ( O.OZI I .I 0.07.1 I I 0.07.l I I I O.OXJ
0
0
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>-
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V')
00742
PROGRA~: Alum-Adsorbed Yeast Recombinant Hepatitis 8 Vaccine,

Study 811.

dose levels of connerc1al hepatitis B plasma derived
vaccine (H-8-VAX) and yeast recombinant hepatitis B
vaccine in the following populations who are initially
seronegative for hepatitis B virus markers:
l. Predialys1s Patients
Lot I 974/C-K446 (20 mcg HBsAg/ml)
Hepatitis B Plasma Vaccine
Lot# 1510J (20 mcg HBsAg/ml)
PRINCIPAL Peter J. Grob, M.D.

INVESTIGATOR: Section of Clinical Innunology
University Hospital
Haldeliweg 4
CH-8O44 Zurich
Switzerland
SECONDARY U. 81nswanger, M.D .• Professor

INVESTIGATORS: Department of Medicine
Nephrology Section
University Hospital
Zurich
C. Descoeudres, M.O.
Inse lspi ta 1
Berne
A. Blumberg, M.D .• Professor
Nephrology
Kantonspital
Aarau
A. Hany, M.0., P.O.
Hemod1alys1s Unit
Kantonsspital
W1nterthur
25151-1
1/22/86
00743
Study 811
SECONDARY H. Iselin, M.D.

INVESTIGATORS: Hemodialysis Unit
(Cont.) Neumunster Sp1tal
Zurich
K. Zaruba, M.D., P.O.
City Hospital Waid
Zurich
W. Herwig, M.D.
Kantonsspital
Chur
H.-J. Gloor, M.D.
Hemod1alys1s Station
Kantonsspital
Schaffhauun
J. Nadig, M.D.
Hemodialysis Unit
Kantonsspital
Winterthur
H. I. Joller-Jemelka, M.O.
Section of Clinical Innunology
University Hospital
Zurich
STUDY LOCATION: University Hospital

Halde11weg 4
CH - 8044 Zurich
Switzerland
25151-2
1/13/86
001IHI
Study 811
STUDY POPULATIO~: One study population consists of 59 predialysis

patients who have renal disease with functional
impairment or end-stage renal disease that will
shortly require dialysis treatment. The other
population is comprised of 11 health care pers·onnel.
Subjects in both populations must be adults of either
sex (pregnant women excluded). The~ 11Ust be initially
negative for all hepatitis B serologic markers, have a
nonnal ALT level, and must not previously have
PROCEDURE: Patients are randomly assigned to one of S groups;

Health care personnel constitute a sixth group.
Group Vaccine/Dose/Reginien
; Recombinant vaccine; 0.5 ml (10 mcg)
at o. 1 and 6 months
2 Recombinant vaccine; 1.0 ml ( 20 mcg)
at o. 1 and 6 months
3 Recombinant vaccine; 2xl.O ml (40 mcg)
4 H-8-VAX; 1.0 ml (20 mcg)
at o. l and 6 months
5 H-8-VAX~ 2x1.0 ~1 (40 mcg)
6 Recombinant vaccine: 0.5 ml (10 mcg)
at 0, 1and61110nths
All injections will be intramuscular. Patients in
Groups 3 and 5 will have the vaccine ad~inistered in a
divided dose (i.e., 2 injections - one injection tn
each of two contralateral lilllbs).
Vaccine recipients will be asked to record their
temperature for 5 days after each injection and to
note any local or systemic complaints. Study
participants will be bled 1 to 10 days prior to
vaccination to verify eligibility for the study.
25151-3
1/13/86
007415
Study 811
PROCEDURE (Cont.): Follo\::1-up samples will be obtained at 1. 3, 6 and 8

months following the initial vaccine injection. Blood
samples will also be obtained at 12 and 24 months from
subjects who are positive for anti-H8s at 8 months.
All serum sa111Ples will be assayed for anti-Hee.
anti-HBs, HBsAg and ALT by the investigator. and may
be assayed for yeast antibody at MSD~l. In addition,
participants who show an anti-HBs titer~ 25 mIU/ml
will have their serum tested to detemine the
proportions cf anti""!, and anti-g_ activity.
RESULTS: PREDIALYSIS PATIENTS:
20 mcg Lot #974/C-K446 at o. l, and 6 months
40 mcg Lot '974/C-K446 at o. 1. and 6 months
20 mcg Lot #1510J at O, 1, and 6 months
40 mcg Lot #l510J at 0, 1, and 6 months
1. Number vaccinated:
Infection #
Vaccine Dose Level _1_ _2_ _3_
Recomb. 10 mcg 14 14 13
20 mcg 14 14 13
40 mcg 13 13 12
H-8-Vax 20 mcg 11 11 10
40 mcg 11 11 10
Seven/eight month serology data are available for
13, 12, and 11 participants who received 10, 20
and 40 mcg injections of vaccine, respectively.
Serology data for 7/8 months of follow-up are
available for 8 subjects 1n each of the
plasma-derived vaccine dose regimens.
25151-4
1/13/86
007ll6
Study #811
RESULTS: (Cont.) Ant1-HBs responses and Gt-'lTs for recipients of

yeast recombinant and plasma-derived vaccine are
surmnarized below:
om l■IU/■1l
Dose I with Ant i..ff8s All ReS00l1Clln
V• ccint level S/td ~2.1 alU/■1 ~10 Vaccinees SIN ?;2. 1 IRIU/lnl ~ 10
ReCOlllb. 1011C9 15 (2/13) 15 (2/13) 0.1 61.1 61.7

20irq 58 (1/12) 58 (l/12) 13.8 213. 7 213.7
40 n:11 64 (7/11) 54 (6/11) 13.6 120.9 196.4
H~-Yax 20incg ZS CZ/8) ZS (2/8) 1.3 101.2 101.2

4011tll 50 (( /8) 38 (3/8) 8.7 251.0 791.5
Refer to Tables l and 2 for ant1-HBs responses and

GMTs through 12 months of follow-up
Clin1cal follow-up data are ava1lable for at least
12 participants. after each injection, who were
enrolled in the 10 mcg dose regimen, 13
participants who received 20 mcg injections, and at
least 10 subjects who received 40 mcg injections of
yeast recombinant vaccine.
At least 5 participants 1n each of the
plasma-derived vaccine dose groups have clinical
follow-up data after each 1nject1on.
The overall frequencies of compla1nts among
vaccinees who received yeast recOlllbinant or
plasnia-derived vaccine are presented below:
25151-5
1/13/86
00747
· Study 811
RESULTS: (Cont.)
Type of Dose Freguenc~ in I b~ Injection 4
Complaint Vaccine Level 1 2 3
Injection Recomb. 10 mcg 0(0/14) 0(0/14) 0(0/12)

Site 20 mcg 0(0/)4) 7( 1 /14) 0(0/13)
40 mcg 0(0/12) 0(0/11) 0(0/10)
H-B-Vu 20 mcg 10(1/10) 0(0/8) 0(0/5)
40 mcg 0(0/10) 0(0/10) 0{0/5)
Systemic Recomb. 10 IIC9 0(0/14) 0(0/14) 8(1/12)
20 IIC9 7 ( l /14) 0(0/14) 0(0/13)
40 mcg 0(0/12) 0(0/11) 0(0/10)
H-8-Vax 20 IICSI 14(1/10) 0(0/8) 0(0/5)
40 mcg 0(0/10) 0(0/10) 0(0/5)

HBV MARKERS (Anti-HBc)

One subject in the 10 mcg yeast recombinant vaccine
group was positive for anti-HBc at 1 and 3 months
after the first injection of vaccine. The sera of
this participant retested negative for ant1-H8c. All
samples were negative for HBsAg and ALT levels were
normal.
Two subjects in the 20 mcg yeast recombinant vaccine
group were positive for anti-HBc at 8 months post the
first injection of vaccine. The patients were
negative for HBsAg and ALT levels were normal. In
both cases, the 12 month follow-up serum samples were
negative for anti-HBc.
A predialysis patient in the 40 mcg yeast recombinant
vaccine group was positive for anti-HBc lgG and
negative for ant1-H8c IgM at 6, 8, and 12 months post
the initial vaccine injection. Serum samples were
negative HBsAg and ALT levels were normal.
25151-6
1/13/86
Study 811
RESULTS: (Cont.) A subject in the 20 mcg plasma-derived vaccine group

was positive for anti-HBc at 1 month after the first
injection. The participant was negative for anti-HBc
at 3 months . Serum samples were negative for HBsAg
and ALT levels were within normal limits.
One participant in the 40 mcg plasma-derived vaccine
group tested positive for anti-HBc at 1 month. The 3
and 6 month serum samples were negative for anti-HBc.
The subject was negative HBsAg and ALT levels were
normal.
There have been no reports of clinical hepatitis in
any of the above vaccine recipients.

A 28 year-old male (Case ~b) (o) with underlying renal
disease and recently 1n1t,ateo he110d1alys1s. died
approximately one month after administration of the
first injections of vaccine. The investigator
reported death was due to vasculitis.
25151-7
1/13/86
Table 1
Antibody Responses l\1ll)ng Prectla1ys1-s Patients fo11CJNlng Vaccination wi t h

10, 20, and 40 IIICO Injections of Yeast Recond>inant Hepatitis B Vaccine
lot , 974/C-K446 at o, 1, and 6 f!onths in Study mn 1
10 IIIC!I 20 IIIC!I - 40 IIIC!I

1,~ilh Arit i -Has GflT (111IU/111Il ,. wi th Anti -HBs «1tT (111IU/11l} \ with Anti-HBs <JIT (111IU/ml l
Re~iden Resoonders Resoonders
T11119 MIU/ml IIIIU/1111 IIIIU/1111 "11 111lU/ml mIU/ml All mIU/m1
(~.) S~2 . 1 ~ 10 "' 1
Vacc\nees 5~2.1 ~ 10 S/~2. 1 ~ 10 vacdnees S/~2.1 ~ 10 S/~2.1 ~ 10 Vaccinees S~2. I ~ 10
0 0 0 .3 -· - ··- 0 0 0. 3 - -- -- 0 0 0.3
(0/1 4) (0/14) (0/1 4) (0/1 4) (O/l3) (0/13)
3 0 0 0.3 --- .~ -- 1 7 o.s 90.0 90.0 0 0 0.3

(0/1 4) (0/ 14) (1/1 4) (1/14) (0/12) (0/12)
6 0 0 0.3 -- 28 28 1.0 23.6 23.6 42 42 1. J 19 .4 19 .4

(0/13) (0/13) (4/1 4) (4/1 4) (S/12) (S/12)
1/8 15 1S 0.1 67. 7 61.1 58 58 13.8 213. 7 213.7 64 54 23.6 120.9 186. 4
(2/13) (2/13) 0/12) (J/12) ( 1/11) (6/11)
12 8 0 0 .4 6 .0 - -- 60 60 8.5 78.S 78.5 40 40 3. 3 117 .3 lt7 . 3

( 1/12) (0/12) (6/ 10) (6/10) (4/10) (4/10)
251S1-8 ...,
Q
~
1/13/86 -Q
fable 2
Antibody Responses 1'nong Predialysis Patients following 11.accination with

20 and 40 nacg Injections of Plasma Oeriwd Hepatitis 8 Vaccine
Lot • 1510J at 0, 1, and 6 ltonths in Study 811
20 mcg 40 fflCg
I with Ant 1-MSs Gl'lf l,!!!IU/■12 I with Anti-Ills GMT lfllIU/111 2
Tim! All Resoonders All ReSOOlldei'S
(Months) SIN ~. 2.1 111U/1111 ~ 10 Vacclnees SIN~ 2.1 111IU/111l :'. 10 S/N~2.1 mIU/1111 ~ 10 1/acdnees SIN ~ 2.1 11IU/111l ~ 10
-- --
0(0/11) 0(0/11) 0.3 --- --- 0(0/11) . 0(0/11) 0.3
3 10(1/10) 10( 1/10) 0.5 29.0 29.0 10( 1/10) 0(0/10) 0.4 6.0
6 22(2/9) 11(1/4)) 0.6 8. 1 13 .0 50(5/10) 40(4/10) 3.7 45.2 78.S
718 25(218) 25(2/8) 1.3 101.2 101.2 50(4/8) 38(3/8) 8. 7 251.0 791.S
12 0(0/3) 0(0/3) 0.3 --- - ·-- 50(3/6) 50(3/6) 13. 1 93.0 220.1
* One responder !Oho received the third injection of vaccine at 3 months was excluded fro111 the SU111Mry .
25151-9 0
1/13186 ...,
0
\JI
~
-
~
co
►
0
.::,
I-
v,
00751

Study 816

recombinant hepatitis B vaccine a1110ng:
serologic markers.
2. health care personnel negative for hepatitis B
serologic markers.
(ant1-HBs negative).
VACCINE: Yeast Recombinant Hepatitis B Vaccine _

PRI MARY Stanley Plotkin, M.D./Stuart Starr, M.D.

34 Street and C1v1c Center Boulevard

Allentown. Pennsylvania 18104
Dialysis, Inc.
1230 Bunnont Road
Oown1ngton, Pennsylvania 19335
25381/1
1/21/86
00752
Study 816

dialysis patients (including previous nonresponders
to plasma-derhed vaccine), and 20-25 health care
personnel, of either sei (excluding pregnant women),
who are negative for HBsAg. ant 1-HBc and anti -HBs,
and have a nonnal ALT level. Dialysis patients
(excluding nonresponders to plasma-derived vaccine)
received any hepat\tis 8 vaccine.

Dialysis patients receive l .0 ml (20 mcg HBsAg) or 2
x 1.0 ml (40 mcg HBsAg) intramuscular injections of
vaccine at 0, 1, and 6 months. Health care
personnel receive 0. 5 ml (10 111cg HBsAg)
intramuscular injections of vaccine according to the
injection of vaccine. Post-vaccination blood
sa111>les are obtained at l, 3, 6, B, 12 and 24
months.
anti-HBc, and ALT. Samples may be tested for yeast
titer~ 25 mlU/ml may be tested to determine anti-~
and anti"i!, subtype specificity.
25381/2
l /21 /86
00753
Study 816
RESULTS: DIALYSIS PATIENTS

20 mcg Lot 974/C-K446 at 0, 1, and 6 months *
40 mcg Lot 974/C-K446 at 0, 1, and 6 months*
Dose Injection Mo.

(mcg) _1_ ..L ..l..
20 39 34 33
40 36 34 25
One dialysis patient who was initially anti-HBc

posit he received vaccine. The patient has
remained antt-HBc positive through 12 months.
The subject has not developed HBsAg or elevated
ALT levels. At one month , the patient became
antf-HBs positive.
Four dialysis patients (40 mcg dose) received
1.0 ml vaccine 1n the deltoid and l .0 ml in the
buttock.
* Two patients rece1 ved a third 20 or 40 mcg
dose of Lot 986/C-K733.
Serolog1c data at 7/B months are avat lable for
29 dialysis patients who received a 20 mcg dose
and 21 dialysis patients who received a 40 mcg
dose of vaccine.
25381/3
1 /21 /86
CI075ll
Study 816
RESULTS: (Contd) At 7/B and 12 months, anti-HBs responses are as

fol lows:
GRT (IIIIUhll1)
Ti~ 00M 'b Anti..HBs Positill!! All R rs
(Nonths) (IICg) SIN ~2.1 mIU/111 ~10 vaccinees S/N ~2. 1 fi1IW11l ~ 1[
7/8 20 59(17/29) G(lC/29) 7.8 69.1 118.6

94(16/17) 88(15117) 219. 7 331.8 445.5
12
* 40
20 52(15/19) 41(12/29) S.1 49.2 79.9
1r 40 81(17/21) 71(15121) 41.6 107.9 165.6
• Serolog1c results included 1n the above sumary

do not include 4 dialysis patients (40 mcg
dose) who received 1.0 ml vaccine in the
deltoid and 1.0 ml in the buttock.
Ant1-H8s responses at 1 through 12 months are
and 56 dialysis patients following the first,
second and third injections of vaccine,
respectively. Clinical complaints and maximum
temperatures reported fol lowing each injection are
provided in Tables 2-S. In sunnary:
Clinical Dose % Freguenc~ b~ Injection No.

Comolaint !!!ill 1 2 3
Injection 20 8(3/38) 0(0/34) 0(0/33)

Site 40 11 ( 4/36) 3(1/34) 0(0/25)
Systemic 20 24(9/38) 3(1/34) 12(4/33)

40 22(8/36) 0(0/34) 8(2/25)
No serious or alarming adverse · reactions

25381/4
1 /21 /86
00755
Study 816
RESULTS: {Contd) Events reported to 0oBRR

Seven deaths have occurred among dialysis patients
who received rec011b.1 nant hepatitis 8 vaccine Lot
974/C-K446. The investigator does not consider any
of the deaths to be related to vaccination.
6J (6)
l. Case no. a 57 year-old female, died
approximately six months after receiving athird
40 mcg dose of vacc'\ ne. The cause of death was
cardiac arrest.
2. Case no. b) (6) a 57 year-old male, died
approximately one month after receiving a third
20 mcg dose of vaccine . The caus~ of death was
attributed to a myocardial infarction and
end-stage renal disease.
b) (6)
3. Case no. a 49 year-old male, died
approximately four 110nths after receiving a
second 40 mcg dose of vaccine. Death was due to
respiratory arrest, aspiration asphyxia,
end-stage renal and coronary artery disease.
b) (6)
approx1118tely four months after receiving a
second 40 mcg dose of vacc1ne. Death. was caused
by cardiac arrest, atherosclerosis, end-stage
renal disease and 11Ultiple myel0t1a.
b)(6)
5. Case no. a 71 year-old female, died
approx1118te '1y one month after receiving one 20
mcg dose of vaccine. Death was due to cardio-
pulmonary arrest, uremia, chronic renal failure
and abdominal aortic aneurysm without rupture .
6f(6j
approximately tour months after receiving a
second 40 mcg dose of vaccine. The death was
due to cardiac arrest, pulmonary ederaa, and
end-stage kidney disease.
1. Case no. o)l6J a 37 year-old female, died

approximately two months after receiving a
second 40 mcg dose of vaccine. The death was
caused by sepsis, end-stage renal disease, acute
respiratory distress syndrome, infected dialysis
graft, and diabetes mel11tus.
25381/5
1/21 /86
Table l
Antibody Responses Among Dialysis Patients Following Vaccination with

20 or 40 mcg Doses of Yeast Recombinant Hepatitis B vaccine
Lot 974/C-K446 * at 0, 1, and 6 Months 1n Study 816
D1alvs1s Patients
20 fflCQ 40 mca •*
GMT fmlU/1111) GMT (mlU/111\
Tille I with Anti-HBs All Resnonders ,: with Ant1-HBs All Res11onders
(Months) S/N ~ 2. 1 1111U/ml ~ 10 Vacc1nees S/N ~ 2.1 mtu/1111 ~ 10 SIN~ 2.1 mIU/ml ~ 10 Vaccinees S/N ~ 2. 1 mlU/ml ~ 10
;
l 8(2/2&) 4( 1/26) 0.4 5.4 18.5 15(4/26) 8(2/26) 0.6 8.1 11.9 i
I
3 21(5/24) 4(1/24) o. f, 6.5 76. l 52( 13/25) 28(7/25) 2.3 15.0 32.9
6 33(8/24) 13(3/24) 1.0 &.4 21. 7 81(13/16) &3( 10/16) 10.8 21.S 35.2 I
7/8 59(17/29) 48( 14/29) 7.8 69. l 118.6 94( 16/17) 88( 15/17) 219. 7 331.8 445.5 I
12 52(15/29) 41(12/29) 5.1 49.2 79.9 81(17/21) 71(15/21) 41.& 107.9 165.6
..
* Two dialysis patients received a third 20 or 40 mcg dose of Lot 986/C-K733.

** Four dialysis patients (40 mcg dose) received 1.0 ml vaccine in the deltoid and 1.0 ml tn the buttock.
At 7/8 months, 25% (1/4) seroconverted (S/N ~2.1) and developed protective levels of antf-HBs (mlU/ml ~10).
These four subjects are not included in the above sunnary.
25381-11
1/22/86
0
...
0
""
Cl'
Table 2
PATIENT COUNT CLINICAL COHPLAlHTS
RECot16IHANT HEPATl1IS 8 YACCIHt
STUJY I Oi,16
TREATHEHT
LOT tM18ER l CK4q6
DOS£ 20 t1CG
PATIENT CUSS: DIALYSIS PATIENTS
I TOTAL VACCIHtES I 39 PATUHTS I - oos, l I

1-----------------------------
I .----------------------------------------------1
DAYS POST YACCIHATIOH I HUHUER
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I
I l l
O.OXJ ( 5,Jl!I I I t.6)(1 I 2.6i0 ( 2.67.1 I I 2,67.1 ( 7.9l0
I I
FAT18UEIM£Al<HE9' I 0 0 I t 0 0 I 0 2
0 .ox, ( 1.0;0 I t S.31.1 I 0.01. I ( o.or., I , 0.01.J ( 5.37.I
I I
HEADACHE I 1
2.6Y.t (
1 I
2.61.1 I I
•
0. t1. I I o.o:o
0
I
0
1.0,0
f·
I 1
0
o.ox, .(
2
S.31.1
I I
DIG£STIVE SYSTE" I l 0 I 1 0 1 I l 2
2 .6Y.I ( O.OY.1 I f Z,6Y.I f O.OY.J I 2.67.J I I 2,67.J ' · 5.3%)
I I
DIARRHEA I l 0 I l D 0 I 0 l
2 .6Y.I I a.or., I , 2 .61. I ( o. 01. 1 l I o.or.1 I t 0.01.J I 2.67.1
I I I
NAUSEA I
(
0
0.01.) (
0
0.01.,
I
I r ,.,r.,
• (
D
0.01.1
I
I I
l I
2.61.J I I
1
2.6i0 I
1
2,67.1
0
...,
0
...,
'-"
Table 2 (cont.)
PATIENT CDUtT CLINICAL COtff'UlNTS
RECDfl8INANT ffEPATI~IS 8 VACCINE
STUDY 0816
TREATittNT
LOT NUt1BER I CK446
DOS£ 20 ttcG
PUlENT CLASS: DIALYSIS PATIENTS
• TOTAL YACCJNEES ( 39 PATIENTS) - DOSE 1 •

•---------------------------------------------------------------------------•
• OATS POST VACCINATION • NUt113tR
CLINICAL
Cot1PLAINTS I•----------------------------------------------------------------------------•
O • 1 I 2 • 3 • • • 5 •
WITH
•cot1PLAINTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••• .. l••••••••••••••••••••••••••••••••••••••••••••••••••••••I••••••••••
I
YONJTINI: • 0 • 0 0 0 1 1 • 1
o.o:o I , o.o;o , o.o:o , e.o:o , 2.6:0 1 t.t.:1.> I 1 2.1,:1.1
I I
NERVOUS SYSTEPI I 1 • Cl O O O t I 1
2,67.J I l o.o,o c o.o:o c o.o:o I 0.0:1.J c 0.0:1., I c 2.61.I
I I
YERTIGOIOIZZlNESS I 1 I O O O O t I l
2.6:'.) I ( 0.0Y.) I o.o:o C o.o:o f O.OY.J ( o.o:o I f 2.6Y.I
PSYCHIATRJC/8EHAVIORAL • 1 I I O O O O I I• 1
2,6'0 I C O.OY.I ( o.o;o ( 0.01.I ( o.o:io ( 0.0;1.t f ( t.6:!I
I I
INSOttflAIDJST\JRBED SLEEP I 1 I O O O O I • l
I I !.6l0 I I O.OlO I 1.0:0 I I e.o:t.t • I o.oY.> f 0.0:!J I I !.6:1.I
-----------------------------------1----------•----------•----------l----------l----------l----------l----------•-----------
PtRsONS MITH CfflPLAIMTs I " I " I s I 2 I 1 I 1 I I 11
I 1 10.sY.1 I c 10.s:o I c n.2;0 I I 5.37.1 I I 2.6:1.) • c 2.,:0 I I c 28.9:1.I
-----------------------------------l----------l----------l----------l----------l----------1----------1----------1-----------
PtRSOHS NITII HO CDHPUINTS I 34 I 34 I 33 I 36 • 37 I 37 I I 27
I I 89.57.> I c 69.s:o I I 86.8:0 I f 94.77.1 I c 97.47.) • f 97.4:o I I f 11.1:1.,
-----------------------------------1----------•----------•----------•----------t----------1--·-------1----------1-----------
PERsONS MITH NO DATA I e • o I o I o f o I o I I o
• , o.o:o I , o.o:o I I o.or., • , o.o,o f , 0.0:1., I , 0.0:1., • • 1 o.ox,
....U'I
0
OJ
Table 2 (cont.)
PI TJEHT COUNT CLJHICI L COffl'LAINTS
RECOt1BIHAHT HEPATI~lS 8 VACCIHE
STUD Y I 0816
TREATNENT
LOT HUt'IIER I Cit<+"
DOS£ I 20 t1CG
PATIENT etas, : DIALYSIS PATIENTS
I TOTAL VACCINE ES I 3._ PATI ENTS I - DOSE ! I

1---------------------------------------------------------------------------I
I oa,s POST VACCIHATIOH I HUl1BER
1----------------------------------------------------------------------------I
CLIHICAL
COtff'LA IHTS
................................... •
, D
.......... •
, l
.......... J 2
,
.......... I 3
, • 4
......................
-----------------------------------t----------1----------1----------1----------1 ----------1
• 5
.......... •
, ,
Mint
lt0!1PLAINT5
.......•..•..........
----------1----------1 --- .______ _
SYSTEHIC I O I O I O I O I 1 I O I • 1
I I D.OY.I I I O.OY.I I I O.DY.I I I O.OY.I I I 2.9i0 • I O.OY. I I • C 2 . 97. 1
----------·--------------------------------------------------------
1 I I • I I
ffl!OLE BOUY/GENER AL I O I O I D I D I 1 I D I I 1
,.ox, I I O.OX J • I o.o;o I I D.07.J I I Z.9Y.J • I D. OiO • I I . z .9;0
I • 1 I I I I
fATI&UE/NlAKNESS • o I o I D I o I 1 I o I I 1
I ( O.D?. J • ( 0.07.J I I O.D?.I I I O.DX J I I Z.9i0 I I 0,07. I I I I t .97. J
-----------------------------------1----------I----------
PERSOHS MITM COHPLAINTS I I I I
I----------I----------I----------I----------
I O I D I. 1 • O
I----------I-----------
• I l
I I o.ox, I ( O.OY. J I C O.OlO I ( 0.07.J I I 2.9l0 I I O. OY. I • I C 2.9Y. J
-----------------------------------•----------1----------1----------1----------1----------1----------1
PERSONS MITH HO CONPLAIHTS I :,, I 3• I 34 I 34 I 33 I 34 I
----------1-----------
I 33
I UOD.OY.I I U OO.O?. J I ClOO.OY.I I U00.07.I I C 97. 17.l I ClOD . OiO • I I 97 . lY. J
-----------------------------------1----------l----------l----------l----------l----------•----------
PERSOHS MITH HO DATA I O I I I O I O I O I O
I----------
I •I-----------
O
I t D.07.J I t 0.07. J • C O.Cl?.I I C 0 .07.J • C 0 .0?.I • I o.o:o I I I O. OY. I
0
0
.....
v1
"'
Table 2 (cont.)
PATIENT COlHT CLINICAL CONPLAINTS
RECOtlBINANT HEPATITIS 8 VACCINE
STUDY I 0816
TREATI'IEHT
LOT NIHIER cM.-6
DOSE I 20 11CG
• TOTAL VACCINE£! { 32 PATIENTS J - DOSE J •
I•----------------------------------------------------------------------------•
• DAYS POST VACCIHATIClN I NUl18ER
CLINICAL
COHPLAINTS
•----------------------------------------------------------------------------1
• e I 1 • 2 • J • It • 5 •
NITH
•cottPLAINfS
••••••.. •••••••••••••••••••••••••••••••••••••••••••'"'••'"'l••••••••••••••••••••• •••••••••••••••-•••••••••••••-••••u•••••~•
-----------------------------------1---------l----------l----------l----------t----------l----------l----------•-----------
srsnHIC • 1 I Z I J • J • 1 I J I I 4
I ( 1.1;0 I ( 6.3'0 I I 9.4:t.l • ( 9.4Y.l I ( 3.1;0 I I 9.ltY.l I . • I U.SY.I
----------------------------------------------
I
---------- ------------------------------------------------------------------
&MOLE BOOY/t:EHERAL I 0 1 1 1 0 0 l
O.OY.l ( J.llO I J.UO ( J.1)0 I o.o,:, ( 0.0)() ( 1.1;0
9EH9ATIOtf OF MARlflM, GENERAL I 0

o.o,o
1 1
3 .1?.J
1
J.UO •
o.o:o
0
o.o:o I
l
J.UO
3.UO
' '
I ( (
INFECTIOUS SYNIIROttES I 0 0 0 0 0 1 1
o.o;o ( ,.o;o ( o.ox, ( O.OY.l ( 0.0)0 ( 3.1)(1 ( J.lY.l
JNf'LUENZA, HOS I 0 0 0 0 0 l l
O.O)(J I O.OY.l O. OY.I o. 07.J O.OY.I 3.1)(1 J.UO
' '
( (
RESPIRATORY I 1 1 1 I 1 !
' t
3,UO 6.J:O 6.3?.l
'
J.1?.I ( J.lY.l J.lY.J ( ( 3.lY.J (
UPPER RESPIRATORY IHl'fCT., NOS I l 1

' 1 l 1 1 l
3.un 3.1?.l 3.17.J 3,1)0 3,UO ( 3.1?.l (· ,.1;0
'
(
IIROHCHlTIS, NOS I 0
' a 0 0
' a 1 l
o.or., a.or., o. o:r., 0,0)0 J.1?. I I J. l?. l
O.OY. I
'
( ( ( (
NERVOUS STSTffl I 0 0 1 l 0 0 l
I ( J.1:0
o.o;o 0.0Y.I I I J .1?. I 0.0Y.J
' 0.0iO
( J.lXJ
TRENOR I D I o I l I 1 I o I o I I l
I C O.OY.l • C o.OY.I I ( J.UO I I J.lY.I I ( 0.O)O I ( a.or., I I ' . J.lY.J
-----------------------------------•----------•----------l----------l----------l----------l----------t----------
PtRSOl5 WITH COffl'LAINTS I 1 I Z • 3 • J I l I J •
l-----------
I 4
I t :s.uo I c 6.liO I I •.4?.I I t 9 . 4?.J I c 3.1:0 • I 9.4;0 I I I 12.57.l
-----------------------------------1----------l----------l----------•----------t----------l----------
PERSOHS MITH HO COHPUINT9 I 31 I 30 I t9 I t9 I 31 I l!9
l----------l-----------
I I 28
I t "6.97.1 I I 93.8Y.I I t 90.6XI I I 90.6Y.J I l '6.97.1 I f 90.6Y.I I I t 87.SY.l 0
0
-4
0-
0
Table 2 (cont.)
PAT[ENT COUNT CltNICAl CottPLAINTS
REC011BINANT HEPATl~IS 8 VACCINE
STUDY t oa1,
TREAfflENT t
LOT t«Jl18ER t Ck4,6
DOSE I 20 HCG
PATIENT CLASS• DIALYSIS PATIENTS
I TOTAL VACCINE ES I 32 PATIENTS I • DOSE 3 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I llUl1BER
CllHtCAl
COt1PLAIHTS
l----------------------------------------------------------------------------1
I O I 1 I t I J I 4 I 5 I WITH
ICDt1PLAIHT9
••••••••••••••••••••..'"'•••••••••••l••..••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS Willi HO DATA I O I O I O I O I O I O I I 0
I C ,.oY.J I C 0.0)0 I I O.0Y.I I I o.or., I I O.0iO I I o.o;o I I I o.o;o
0
0
-
~
0-
Table 2 (cont.)
PATIENT COUNT CLlHICl l COl1PlAJNT!I
RECOl18IHAHT HEPATIT,s 8 VACCINE
!ITU!IY I 0916
TR£lTt1ENT
LOT Hllt18tR I CK733
DOSE I Zt HC6
PATIENT CLASS: DIALYSIS PATIENTS
I TOTAL VACCIHEt:, ( 1 PATIENTS) - OO!IE 3 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I Hlltf9ER
CLINICAL 1---------------------------------------------------------------------------- I WITH
Cot1PlAINTS I O • 1 I Z I J I ~ I 5 I IC011PlAIHT!I
••••••••••••••••••••••••••••••••••• ••••••••••• l•••••--••• l•••••••••• l•••••••••• l••••••••••l•••••••••• l•••••••••• I••~•••••••
----------------------------------- l----------l----------l---------- •----------1----------I----------I----------I-----------
P£R!IOHS 111TH COHPUIHTS I O I O I O I t I D I O I I 0
• c 0.01.t I t 0.01.1 I I o.or.1 I I o.ox, I I a.ox, I c a.ox, I I I o.ox ,
-----------------------------------1----------I----------I----------I----------I---------- I----------I----------I-----------
PERSOHS W ITH HO C011PUIHTS I l I 1 I 1 I 1 I l I l I I l
I 1100.oxt I uoo.o,o I 1100.o;eJ I uoo.or., I ·uoo.oz1 I 1100.or.1 I I 1100.or.1
-----------------------------------1----------•----------I---------- I----------I----------I---------- I----------I----· ------
PERSONS MITH t10 DATA I O I O I D I O I O I o I I D
I ( o.o:o I ( O.OiO I I O.OiO I ( O,OY. ) I ( O.Ol'!I I ( D.OY.) I I ( O.D?.)
0
0
""
Cl"
N
Table 3
PATIENT COUNT NAXIt1Ulf TElfllERATUlfES
RECOttBINANT HEPl TIT~S 8 VACCINE
SlUl>Y t 0816
fflEAmENT
LOT NlHIER CK4c\6
DOS£ 20 HCG
I TOTAL VACCIHtES C 39 PATIENTS) - DOSE 1 I

Il-------------------------------------------------------------------------------------
DAYS POST VACCINATION 1I NUHBER
HAX TEtfl'ERAT\JRE
IDEGF,ORlll
........................ I
, O
.......... I 1
,..........,
l-----------------------------------------·---------------------------------------------1
f Z f 3
..........•.......... I 4 f J
..................... ,
I
,
MITH
,
.......... f ..........•..........
l11A><TEHP
HOIU'1 U I 11 I 11 I 11 I 11 I 11 I 11 I I 11
n.77.1 I c n.n , I , n.r1.1 I , n.11.1 I c n. 4 7. 1 I c M.47.I I I c 29 . no
I I I I I I I
< 99 I 14 I 18 I 19 I 18 I 16 I 16 I 8
37.87.1 I c 48.67.J I c !Jl.41.J I I 48.6l0 I I 45.77.1 I I so.o,o •I I C 21 ,67.I
I I I I I I I
99 • 99. 9 I u I 1 I 1 I 7 I 7 I 4 I I 16
31!.4Y.) I I 18.97. ) I C 18.9"1.I I C 18.9%) I I H,07.1 I C 12.57. 1 f I f 43.2:'.I
100 - 100 . 9 I o I 1 I o I 1 I 1 I 1 I I z
I I ,.01.1 I I t.n , I C 0.01. ) • C t.TI.) I C t.,:o I I 'J.UO I I ( 5 . 47.J
-------------------- ----1----------1----------1----------1
Tl'.HPERAT\JRE TAKEN I J7 I 37 I 37 I
----------1
37 I
----------1
35 I
---------1---------------------1-----------
32 I I 37
I I 94.9:r.l I I 94.9:r. l I C '4 . 91.) I C 94.9:'.I I I 89.7l0 I I 82,UO f I I 94.9:0
------------------------l----------l---------l----------l----------
nttP£RATURE NOT TAKEN I Z I t I t I t t----------
I 4 Il---------
7 Il---------------------l-----------
I 2
I C 5,11.1 I I 5 ,11.J I I 5 , 17.1 I c 5,liO I C 10.37.1 I I 17,9;0 • I I 5.uo
~
0
""
O-
u,!
Table 3 (cont.)
PATIENT COUNT NAXI,_.., TENPEIIATURES
RECOtlBINANT HEPATI T1S B VACCINE
ST\JU Y I 0(116
TRIEATHENT
LOT NlfflEII CK4"6
DOSE I 20 NC&
PATIENT CLASS: DIALYSIS PATIEffTS
I TOTAL VACCIHEES C 34 PATIENTS! - DOSE 2 •

1------·
I ---------------------------- ----------------------------------------------------
DAY! POST VACCINATION
•• MltfflEA
,I..........,I
1-------------------------------------------------------•-------------------------------•
HAX TEHPERA~ !
CDEG F, ORAL I
........................
I O I 1 • I! I 3
, I 4
,• S • I
, ,
• tfA)(WITH
TEMP
..................... .......... ................................ .......... ..........
I I I .1 I •
HOAHAL I 15 I 15 I 15 I 15 I 1S I 15 I • 15
I f 46.97.1 I C 45.SiU I C 44.UO I C 45.s;o I I 45.SY.I I f 46 . 9)0 I I I 44.lY.I
I I • I I I I I
< 99 I 11 I 15 • 16 • 16 I n • 16 I I 10
I f 34 . ltlO I I lt5.51.I • C lt7,ll0 I I 49.51.1 I c 39,ltY.1 • , so.ox, I I t 29. 4Y.J
I I I I I I I I
'9 - 99.? I 6 I :, I 3 I 2 I s I 1 I • 9
I l lll.8Y.I I C 9.UO I C e.e,n I I 6 . UO I ( 15.27.1 I ( 3.UO I I C 26.SY.J
------------------------l----------l----------l----------
TEHPEIIATUIIE T AKEH I 32 I JJ I J4
l----------l----------l---------1
I 3J I JJ I 3t I
---------------------1-----------
I 34
I 1 ?4.UI I c ,1.i:o I 1100.01.1 I c ,1.11.1 I c n.11.1 I c 9't.Uo I I 1100.0;,.1
------------------------l----------l----------l----------
TEtff'EIIAT\JAE NDT TAl<EH I I! I 1 I O
l----------l----------
I l I 1
l----------1
• 2 I
---------------------1I -----------
0
I I 5.9,o I I 1! .W.I I C O.OY.I I I 2.9l0 I I 2.91.1 I l 5.97.1 I I l O. OY.l
0
...,
0
O'
.t;:
Table 3 (cent.)
PATIENT COUNT NlXIHU1 TENPERATUSIE9
RECDttBINlNT HEPATITIS 8 VACCINE
STUDY I 0816
TREATl1£NT I
LOT talt1BER I CK446
DOSE I to ttCG
-----------------------------------------------------------------------------------·----------------------------------------
I TOTAL YACCIHEES C 32 PATIEHTS) - DOSE 3 I
l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATIOH I ffllt18ER
1---------------------------------------------------------------------------------------l
NAX TfNPERATURE
(DEG F, lmAU I O I l I t I J I 4 I
,5 I I
, I NAXMITH
TEHP
......................................................... .......... .....•....•.......•..•..........•.......... .......... ,
HORttAl I 15 I l!J I 15 I 15 I 14 I 14 I · 14
so.ox, I c 4&.47.J I c so.o,o I 1 50.o;o I c 45.t?.) I c 46,r✓., •I I c tt5.27.I
I I I I I I I
< 99 14 11 I 12 I lJ I lJ I 7
11
• C 36,TY.I •
IC 45.21.) •
IC 36,7)0 IC 40,0::0 IC •U.97.) If 4J.J7.I. • I I 22,67.)
I I I I I I I
99 - 99.9 I J I 2 I J I t I 3 I 2 I I 7
I 10,0Y.) I C 6.57.t I c 10,07.) I c 6.77.) I I 9. 77.t I t ,.no I I I 22.6:0
I I I I I I I
100 - 100.9 l I 0 I l I 0 I l I 0 I I 1
• 3,:,;,!) I I 0,0iO I I 3, 37. I I I o.o:o I c J.27.1 I I o.o:r., I I I J.27.1
101 - 101.9 I o • o • t I l I o I l I I 2
I I o.o,o I C 0,07.) I f 0.07.J I C J,J7.J I C 0,07.J I C J.J7.J I I I 6.57.I
------------ .-----------1----------l----------l----------l----------l----------l----------1---------------------1-----------
TENPERATURE TAAEH • 30 I Jl I JO I JO I 31 I 30 I I Jl
I c 93,&;() I c '6.910 I I 93.er.J I C 93,e;o I I .96.97.J • I 93.&:'.J I I t 96,97.J
------------------------l----------•----------l----------l----------l---------1----------1---------------------l-----------
TENPERArulE HOT TAKEH I 2 I l I 2 I 2 I l I 2 I • l
• c 6.37.J I c J.17.J I I 6,3%) I C 6,J:'.J I C J,lY.J I C 6.JY.t I I I J.17.I
0
Q
.....
0-
111
Table 3 (cont.)
PATIENT COUNT Hl XI ~ TElff'ERl l\JlES
REC0119I NAlfT HEPATITlS IS YAttitlE
STUDY t 0816
TREAT11£HT
lOT HUM8ER CK7JJ
DOSE :to tte&
PATUHT CU !l!St DillYSIS PATIENTS
I TOTAl YACCIHUS I 1 PATIENTS I - 005£ 3 •

1I ------------------·---·-------··---·---·------·---·----------··-····-----··-·-·-··---·-1
DAYS POST VACCINATION I tltJH8ER
HlX TEHPERAT\JIIE
tOEG f, ORAll
1I ---------·-·-•--------·--------•-·-··-·----••-----•·•-·----·---·---•----·-·---------···1
O I 1 I Z I 3 I It • 5 I •
WITH
• HA>< TEMP
· · · · · · · · · · · · · · · · · · · · · · · · • · · · · · · · · · · · · . . . . . . . . . . . . . . . . . . . . , •••••••••• • •••••••••• • •• lflf •••••• • •••••••••• • •••••••••• • ••••••••••
I I I I I I I I
HORHAl • 1I 1 I 1 I l I 1 I 1 I I 1
• u oo .o,o I u oo.o,o • noo.o:o I 1100.oY.1 • uoo.ox1 I uoo.o:o I I noo .o;o
------·-----------------•----------l------·-·1·-·-·-----1
TEHPERATURE TAKEN I 1 I 1 I 1 •
·-···---·-•·-··----·-1----·----1---------------------1
1 • 1 I 1 I I
--- .______
1
_
I noo . 01.1 • u oo.or-1 I u oo.o;o • 1100. 07.1 I uoo.o?-1 • noo.o:o • • 1100.0:0
------------------------1
TEHPEAAnmE NOT TAKEN I
----------l----------l----------
o I o I o l-------·--1
I o I ------···-•-··-·---·-1---·---··--··-·------l-·-----·-·-
o I o I I 11
I ( o.o;o I ( o.o:o I C o.o::o I t O. Oi'.I I C , .o;o I t 11.117.1 I I ( Cl .Iii'.)
0
0
....
0-
0-
Table 4
PATIENT COUNT ClINICAL Cot'IPLAINTS
RECotl'IIHANT HEPATITIS 8 VACCINE
SlUJY 0816
TREAfflENT
LOT t-MfflER I CK446
DOSE 40 ttCG

l----------------------------------------------------------------------------1
CLINICAL
C0t1PLAIHTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I J I 4 I 5 f
WITH
lt0t1PLAINTS
••••••••••••••••••••••••••••••••""•1••••••••••1••••••••••1••••••••••1••••••••••·
I I I I
1I ••••••••••1••••••••••1••••••••••1••••••••••
I I I
REACTION, LOCAL !INJECT. SITE) I l I 1 I 1 I O I o I o I I 4
I C a . J )O I C 2.a:o I l 2.e:o I I 0.0)0 I I o.o:o I C o.o:o I I I 11.1)0
-----------------------------------l----------l----------l----------l----------l----------1----------1----------1-----------
SORENESs I z I 1 I 1 I o I o I o I I 3
I l 5.6)0 I C Z. 87.) I I 2.87.1 I I 0.07.) I I o.o;o I C o.o:o I I I 8 . 37.I
I I I I I I I I
STIFFNESS/TIGHlllESS I 1 I O I O I O I O I O I I 1
I , z.81., I 1 0 . 07.1 I c 0.07.1 I 1 0.07.1 I c 0,07.1 I c o.o:o I I c 2.ex,
I I I I I I I I
ECCHfflOSIS I l I D I o I O I o I o I I 1
I C Z. 8Y.J I C 0.1:0 I C D.0Y.) I I 0,07.J I l o.o:o I C 0,07. ) I I l z.e:o
---------------------------------1----------1----------l----------l----------t----------l----------l----------l---·
svsnt11c I z I s I s I I! I 4 I z I I
-------
e
I C 5.67.J I C e.J7.I I I ll. 97.1 I I 5,67.1 I C 11.uo I I 5.67.) I I I 22.t:o
----------------------------------------------------------------------------------------------------------------------------
I
tlltOLE BOOT/GENERAL I z I z 3 I! 3 l 6
5.6Y.J I c 5,6Y.) C 0.37.I I 5.6?. ) I 8.37.1 1 Z.87.1 I 16. T/.1
I
SENSATIOtl 01' WARmH, SENERAl I 1 I l 1 I 0 0 1
Z.87.JI I Z.87.) C t.87.1 I 0.07.) I 0.17.) I o.o;o I Z.87.1
I
FATI&UEINEAKNESS I l I l 1 1 t I 3
1 z.8,n I c 2.87.1 ( 2.87.1 I Z.87.) I 5 . 67.) C 0.07.) 1 8.J;O
tlALAISE I D 0 1 0 0 0 1
I c 0.07.J C 0.07.I l 2,87.1 I 0.0?.J ( o.o;o ( o.o;o ( f.8:0
I
HEADACHE I 1 z 1 1 1 0 2
I c t.87.) ( 9.6:0 ( t . OiO I Z. 87.J I z.e:o C o.o:o l . 5.67.)
I
lIGffllfEADED I 0 D 1 0 0 0 1
o. 07.) C •• 07., l z.er.1 I 0.07.1 I 0.07.I I a.o:o I l!.8i0
II '
ILLNESS, HOS I 0 0 a a a 1 1
D.0Y.I l o. o::o I 0.0Y.I I O.OY.) I 0.07.I ( 2.87.1 I l!.87.I :;,
...a-
0
...
Table 4 (cont.)
PATIENT COUNT CLINICAL C011PLAIHTS
RECot18JNAHT MEPATI11S B VACCINE
STUDT : 0816
TR U mrnT
LOT NUMBER CM46
DO!lf '10 t1C8
PATil!HT CLASS: DI ALYSIS PATI[NTS
I TOTAL VACCINE ES ( 36 PATIENTS I - DOSE 1 I

l----------------------------------------------------------------------------1
I OATS l'OST VACCINATION I NU18ER
CLINICAL
COMPL&IHTS
1---------------------------------------------------------------------------I
I o I 1 I t I 3 I " I 5 I
MITff
ICot1PLA1NTS
tttt••••••••••••••••••--•••••••••••••I•••••••••• ••••••••••••••••••NW•••••••••••••••••••••••••••••• ••••••u•••lo~••••••••
I
RESPIRATORY I 0
o.o::o (
1
t.87. 1 (
l
t. 87. 1 ( •
0. 07. J (
0
a.o::o I
0
o.o:o I
1
2,8i0
II '
PNARTNGI TIS I SORE THROAT I I 0 1 l a 0 a 1
o.or. , ( t.8)0 I t . 87. 1 ( 0.07.I ( 0. 07. l I o . o::o I Z.8i0
11USCULOSKl:ltTAl I 0 0 0 0 1 1 z
O.OlO ( 0.07.I C 0.07. 1 ( 0 . 07.J ( .2.er.1 I 2.e::o I 5.&)0
tfUSCLf CRAffl>S I
(
0
o.o,o (
0
o.o::o (
D
0.0)0 ( •
o.o:o (
1
t.8Y.I I
0
D, 07.I C
1
2.e::o
ARM PAIN I 0 0 0 0 0 l 1
o .or. , I o.or., C 0 .07.1 ( • . or., ( 0 . 0)0 I e.e::o ( z.e;o
DIGESTIVE STSTE" .I 0 0 l 0 1 l 2
O.OY.I ( O.OY. ) I t .e,o ( o.or., ( t.8)0 I f.8)0 I s . ,r. ,
tfAUSEA I 0 0 D D 1 0 l
0.0)0 ( o.o:o I O. DY. ) ( o.o:o ( t.e;o I O. 07.l I t.er. ,
VOHITIH6 I 0 0 0 D 0 1 1
o.o:o ( O.OY.) I 0 .07. J ( 0 .07.) ( 0.07.I I z.e?.1 I Z.87.l
APP£TITIE INCl'U SED I o I O I 1 I O I o I O I I 1

_ I , o.o:o I , o.o:o I c z.e;o I , o.or., I t 0.0?.1 I 1 0.01.1 I I I t.e1.,
-----------------------------------1I ----------1----------1----------1
PEllSOtlS NITH toffl'LAINTS 5 I 4 I 6 I
----------l---------1----------I----------I-.
t I tt I 2 I I
---------
9
I I u.,1.1 I « 11.17.J I 1 16.7:Y.J I I s.,:o I 1 11.17.1 I 1 !1.6?.l I I 1 2s.o::o
-----------------------------------t----------l----------1
PERSON5 NITM NO COMPUIHTS I 31 I 32 I ----------1----------1----------I----------I----------I--.
lO I 34' I 3Z I lit I I --------
27
I I 86.11.1 I ( ee.,r., I ( 83 . 37.J I I 9",4'7.J I I e&.97.1 I C 9•L 't?.I I I I 75.0)0
-----------------------------------1
PER,otis WITH NO DATA I
-- .-------l----------l----------l----------l----------1----------1----------1-----------
O I o I O I o I o I O I I o
I « o. 01.1 I « o. 07. J I t o. 07. 1 I l o. or. J I « • •ox I I l o. 117.1 I I I o. or. J
0
=>
'"'
O'
(JI
Table 4 (cont. )
PATIENT COUNT CLINICAL Cotff'LAINTS
RECOM81HANT HEPATITIS 8 VACCINE
Sl\JOY 11816
TII U TffENT
LOT NUt18ER 1 CK446
DOSE 40 t1CG
PATIENT CLASS: DIALYSIS PATI ENTS
• TOtAL VACCINEH I 3r. PATJENT!I J - DOSE 2 I

•----------------------------------------------------------------------------•
• DAYS POST VACCINATION • ~ER
CLINICAL
Cot1Pl.AINTS
l----------------------------------------------------------------------------1
I O • l I 2 ' I l • 4 • 5 I
WITH
IC011PLAINTS
••••••1t11•••••••••••••••1t11•••••••..••••••••••••l•••••••••• •••••••••••••••••••••••••••••••••••••••-••••••••••••••I••••••••••
I • I I • I • I
REACTION, LOCAL UHJECT, SITEI . • l • 1 • l • l I 1 • l I I 1
• C 1!,9l0 • I Z , 97. J I t Z,97.J I I Z,91.J • C 2,9;0 • C Z.9:0 • I I 2.Cl7. I
-----------------------------------•----------•----------•----------•----------•----------•
ECCHlt1051S • 1 • 1 • 1 • 1 • 1 • ----------
1 •----------•-----------
• • l
• C 2. 91.1 • C Z. 9Y. I • I Z. 9Y. I • ( ! . 9l0 • C 2. 97. I • C 2. 9l0 • • C 2. 9Y. J
----------------------------------•----------•----------1----------•----------•----------•----------
PERSOHS NITH CONPLAINT5 I 1 I l I 1 • 1 I 1 • 1
•----------•-----------
• • l
• C 2 .9'0 • C Z,9Y. I • I !.9l0 • I Z,9i0 • C 2,91.1 • I Z,91.1 • • I 2.9Y. J
-----------------------------------•----------•----------1----------
PERSOHS NI 1" HO Cot11'LAUfTS I 33 • 33 • 33 •----------•----------•----------
I 33 I 33 • 33 •----------•-----------
• I 3l .
• C 97.llO • I 97.lY.I I I 97,lY.J I I 97.llO I I 97.11.J I C 97.U!I I • C 97.llO
-----------------------------------•----------•----------•----------1----------•----------l----------
PERSONS NITH NO DATA • 0 I O I O I O I O • 0
•----------I---
I •
·-------
0
• C a.OT.I I C 0.0Y.I • C o . or.1 • I o.a:<J I I 0.0)0 • C 0.07.1 • I C o. o;o
0
....,
0
0-
,0
Table 4 (cant.)
RECOMBINANT ffEPATir1s 8 VACCINE
!ITUDY 08 16
Tl!U TNENT
LOT lllllt8ER Ck4U
DOSE I U ttCG
PATIENT CLA!l!I : Dl l LY!II!I PATi att9
I TOTAL VACCINEES f 24 PATIENT!! I - IIOSE 3 I

l----------------------------------------------------------------------------1
• DAY!I POST Vl CCINATIOtf I I-AJH8EI!
CLINICAL 1--------------------------------------- --- ----------------------------------I WITH
COt1PLAINT!I
,
I O • 1 I 2 I l • 4
, I 5 I
, ICONPLU NT!I
................................... ..........•..........•.........• .......... .......... •.......... ..........•..........
-----------------------------------l----------•----------l----------l----------
,
s,snt11c • 1 • I I 1 • 0 Il----------l----------
O I II I•----------l-----------
• 2
I f 4. 27. 1 • f 11.07.1 I f 4 .27.1 • f 11.07.1 I I 11.07.I I I 11.0:0 I I f 8 .3?.I
----------------------------------
1 I I
llffOU BOOY/GENERAl I 1 I D I O I o I O I O I I l
4.27. 1 • l o.o:o • I t .07.1 • c o.o,o I I 0.11:0 I f o.o:o I I t 4 .2:0
•
HE ADACHE I 1 I o II o
•
I D
I
I o
I
• o II •
I 1
4.2:0 I f 0.07.J I C 0 .07.I I( o.o;o I I 0 .07.1 I I o.a:o I I I 4 .2'!1
I I I I I I I
NUSCULOSl(El£TAL I O I O I 1 I O I O I O I I l
o.07. J I I 0 .07.1 I I 4. 27.1 I I o.o:o I I o . o;o I I o . o:o I I 1 1t.2z1
I I I I I I I
HAND CRAHP!I I O I t I 1 I O I o I o I I l
. • f O.OXJ I I O.liO I I 4 .2:0 I f 0.07.J I I o.o:o I I o .o::o I I f 4.21!1
-----------------------------------1---------- I----------I----------I----------I----------I---------- I---------- I--. --------
PERSONS MITH COHPLAINT!I I 1 I D I l I o • o I O I I 2
I I lt.2'0 I f a.oio I I 4 .2:0 I ( O.OlO I I a.o;o I I 0.07.I I I I 8 .3?.I
-----------------------------------1---------- l----------•----------I--------- .1----------1----------1---------- 1-----------
PER!IOHS MITH NO CottPLAINTS I 23 I 24 I 23 I 24 I 2lt I Zit I I 22
. I, -,s.ex, I noo.ox, I 1 ,s.s?.1 I u oo.o?. 1 I 1100.0?.1 I 1100.a,o I I, ,1.7x1
-----------------------------------•---------- l----------l---------- 1----------1----------1---------- I----------I-----------
PERSOHS Willi NO DATA I O I O I O I O • 0 I O I I 0
I I 0.0?. J I I 0.0?.I I ( 0.0)0 I I 0.07. 1 I I 0.0?.I I f 0.0)0 I I I , .ax,
.........
0
0
Table 4 (cont.)
RECOHBINAHT HEPATI~IS 8 VACCINE
SfUDY I 01116
TRU 'ffltNT
LOT NUl18Eff CK733
DOSE ltO l1CG
PUIENT CLASS• DIALYSIS PATIENTS
I TOTAL VACCINEE!I C 1 PATIENTS I - DOSE 3 •

•----------------------------------------------------------------------------
I DAYS POST VACCINATION •• NUt18£R
CLINICAL •-------------------------- ----------------------------------- --------------· • WI TH
cONPu t ms I • I 1 I 2 I 1 I " I s I •cot1PU 1Nrs
n•••••••••••••••••••••••••••••••••••••••••••• l••••••••••l••••••••••l•••••••••••••••••••••••••••••••••••••••••••••R••••••••
-----------------------------------•----------t----------1----------1----------•----------•----------•----------
PERSONS MITH COffl'lAINTS I O I O I O I O • e • 0 I I•-----------
I
I , o.ox, • c o. a:'-l I c o.ox, I c o.o;o I c o.o,o I c o.oz , I I c o.oz,
-----------------------------------•----------•----------1----------1----------•----------•----------
PERSOHS MITH HO COMPUI HTS • 1 • 1 I 1 I 1 I 1 • 1 I•---------- •-----------
• 1
I n oo.o:e, • uoo.o;o I uoo. o:o I 1100.ou I n oo.o;o • 1100.oz, • I noo .oz 1
-----------------------------------•----------l----------1----------1----------1----------I----------
PERSOHS NITH NO DATA • 0 • 0 I t I O I O I O
I---------- I-----------
• I a
I C o.o:e, I ( 0.0?.I I ( 0.07.I I C 0.0)0 • ( e.0Y-1 I ( 11 .0Z I I I f 0.0ZI
0
0
....,
....,
....
Table 5
PATIENT COUNT IUXIttJt1 TEHPERlTUIIES
REC0'1BINANT HEPATITIS 8 VACCINE
STIJDY : 0816
TirEAfflEtff :
LOT NUl'8ER I ctc•46
DOSE I 40 NC&
PATIENT CUS9: DIALYSIS PATIENTS
I TOTAL VlCCIHEES C 36 PATIENTS) - DOSE 1 I

Il---------------------------------------------------------------------------------------1
DAYS POST VACCINATION I tuteER
"AX TENPEl!ATUl!E
IDEGF,ORAU
l---------------------------------------------------------------------------------------1
ID I 1 I! I 3 I 4 I 5 I I
MITH
l11AXTEl1P
-••••••••••••••••••••••I•••---••••--••••••
I
•••••....•l••••••••••I••••••••••
I I
••••••••••••••••..••I••••••••••••••••••••
t«llmAL I 11 11 11 I 11 I 11 11 11
Jl.3l0 C 32.47.J C 31.4:O I C 30.6l0 I I n.un ( 31.4i0 C 30.6?.)
I I
< 99 I 17 17 17 I 18 1 ti Ill 12
SI.SY.I C so.ox, C 48.67.J I I SD.DY.I I C 61.o:o C Sl.4Y.I C 33.3:0
1 I
99 - 99.9 I 4 4 s I 6 I 1 s 9
12.lY.J C 11.8Y.J C 14.]Y.J I I 16.7Y.) I C t.9Y.J I 14.3?.I I 25.0:0
I I
100 - 100., I 1 z t I 1 I z o 3
3.01.I C 5.97.J C 5.T/.J I I t.8Y.I I I 5.7'n C O.OY.I I 8.3;0
I I
101 - 101.9 I o o o I o I o 1 l
I c 0.010 I t o.o:o I c o.ox, I c o.o;o I c t.o:r., I c t.9Y.t I c z.9;O
-----------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEHPERATURE TAl<EN I 33 I 34 I 35 I 36 f 35 I 35 I I 36
I C 91. T/.) I C 94.41.J I C 97.U!t I UGO.DY.I I C 97.27.J I C 97.ZlO I I fl00.07.I
------------------------1----------1----------I----------I----------I----------I----------I---------------------I----------- ,
TIEHPERlTUIIE HOT TAKEN I 3 I I I 1 I O I l I l I I 0
I C 8.3)0 I C 5.6:0 I C Z.8XI I C O.OY.I I C Z.87.J I C 2.8:o I I f 0.0:I.I
...,_,
0
IV
Table 5 (oont . )
PATIENT COUNT "AXIttlJt TEl1PERATUIES
REC0181HAHT HEPATIT_IS II VACCIHE
ST\DY I 0816
TRUnttHT
LOT NUt18£R! I Cl<446
Der.IE flO 1'1CG
PATIENT CLASS : DIALYSIS PATIENTS
I TOTAL VACCINEES ( 3• PATIENTS ) - DOSE ! I

1I ---------------------------------------------------------------------------------------
OATS POST VACCINATIOH II tlllt18ER
NAX TENP£RATUIIE
I DEC F, ORALI
1I ---------------------------------------------------------------------------------------
O I 1 I ! I 3 I 4 I 5 I I
I WITH
I HAX TE11P
••••••••••••••••••••••-•••••••••••••••••••••I••••••••••••••••••••!••••••--••••••••••••••••••••••••--•••••••
I I
•a••••••••
tdttA L I n n I 1J n I 13 ll 13
43 . 31.I « I « 41.6?.I
4 0.67.I C 39.47.l I I 43. 37.1 C 41 .6%1 I 39.ftY.J
I I
< 99 I 10 14 I u 16 I 16 16 11
JJ.J:X) ( 4J .8l0 I I 46.9'0 I ,e.s:o I C SJ.37.I I 50.0lO I JJ.31.1
I I
99 - 99.9 I • I
4 4 4 I 1 J 11
20.81.J I U.SlO I I 1! .57.l I 11!.1'0 I I J.37.1 C 9 .4l0 I 2ft.2l0
I I
100 - 100.9 I 1 l I o e I D o 1
I C 3.31.I C J.UO I I 1. 07.l l 0.0Y.I I l 0.0Y.I C I .0lO C 3.0Y.I
------------------------l----------
TEMPERATURE rAkEH I JO
l----------l----------l----------l----------1----------1
I 32 I 32 I 33 I JO I 32 I
---------------------I---·
I
-------
· 33
I C M.UO I l '4.llO I I '4.17.1 I I 97.lY.l I C 89.2?.I I C M.lY.l I I I 97.llO
------------------------l----------l----------l----------l----------l----------1----------1
n:NPERATURE NOT TAKEH I 4 I 2 I. ! I l I 4 I 2 I
--------------------- l-----------
I 1
I c 11 .a:x, I c s.,1.1 I I s .,:1.1 I , 2.,x1 I 1 11.e:x1 I c 1 . .-.1.1 I I c 2. ,1.1
.:::,
_.,
0
_.,
~
Table S (o:>nt.)
PATifflT COla4T HAXI,_., Tftfl'ERAT\IRES
RECottBINANT HEPATI~IS 9 VACCINE
STUDY I 0916
TREATNENT 1
LOT MHJER t CK446
DOSE : 40 11C6
• TOTAl. YACCINEES ( 24 PATUNTS l - DOSE l I

••---------------------------------------------------------------------------------------
DAYS PO!T VACCINATION •• NU18ER
f1AX lENPERAT\IRE
t DEG F • ORAL)
•---------------------------------------------------------------------------------------1
• 0 • 1 • t I l • 4 • 5 I • WITH
I t1AX TEt1P
..................................................................... ...................... ,.......................Q········
NmlfA L •• 14 I• 14 I• 14 •I 1, I• 14 •• 14 I• II 1,
I t 58.lX I I t 60.97. 1 I C 60.97.1 • C 60.91.I I t 60.91.J I I 58.lY.1 I • I 5 11. JY.J
I I I I I I I I
< 99 I e I e I 7 I 6 I 7 I 9 • • s
• I 33.J;o I I 34.e:o I I l0. 4XI I c 26.llO I C 10.,1. J I c 37.51.J I I I 20.BY. J
I I I I I I I I
99 - 99. 9 I 2 I 1 I 2 I l I z I 1 I I s
I I e.1)0 I 1 4.:sx, I I e.1x1 • 1 n.o:o I I a.n, I 1 4.21.1 I • c tD.s:o
------------------------•----------l----------•----------•----------•----------1----------1---------------------•-----------
TEffl'ER ATIJRE TAKEH I 24 • ZJ • U • 2l • 21 • 24 I • 24
I 1100.01. , I I 95.BX J I I 95.8Xl • I 9s.e:o • C 95.8)0 I 1100.ox , I I U00.OY.)
------------------------•----------•----------•----------•----------t----------
TENPERATIJRE HOT TAKEN • 0 • 1 I 1 • 1 f 1 •----------1---------------------•-----------
• I • • 0
• I 0.0)0 I C 4 .tlO I t 4 .Ui> • I 4.2?.I I C 4 .2Y. l • I O.OlO I I t t . 0Y. I
0
0
...,"
.c
----- - - - -
Table 5 (cont. )
PATIENT COUNT MAXIHl.tt TEMPERATURES
AEt018INANT H[PATIT~S B VACCINE
STIJ>Y 0816
TIIEATMENT
LOT NUttm r CK733
DOSE I 40 11CG
PATIEllT CLASSI DIALnJS PATIENTS
I TOTAL VACCINEES ( 1 PATI ENTSJ - DOSE J I

1---------------------------------------------------------------------------------------
I DAYS POST VACCINATION •I NU18ER
1--------------------------------------------------------------------------------------- I HAWITH
NAX TEffl't'RATURE
lOEG f, OIIALJ I O
•
• 1 •
I
!
......................................................... I
I
J •
,
•
4
..........•.......... • 5 •
,
.....................
I I
•
•
, ,
.......... I ..........
X TEMP
•
.
< 99 • 1 I o I 1 I o I o • 1 • I o
• (100.02 ) • ( o .o:u I ClOO.OY.I I I O.OY.I • I 0.01.I • noo.0:1.1 I • I 0 . 01.1
I • I I • I • I
" - 99. • I o I o • o I 1 I 1 • o • • 1
I C 0.01. ) • C 1. 07. J I I 1 .07.I • 1100 .01.1 I 1100. I Y.) I I 0.07.1 I I 1100.0Y. J
------------------------l---------l----------1
TEHPEIIATVRE TAKEN I 1 • 0 •
----------l----------l----------1----------1
1 I J I 1 I 1 I ---------------------•-----------
I 1
• uoo.01. 1 I c 1 .01.1 • u oo.01.J I 1100.01.1 • uoo.01., I noo.01.1 • I 1100.01.,
------------------------•----------
TEHPERAT\IRE NOT TAKEN I D I•----------•----------l----------l----------l----------1---------------------1
l • 0 • 0 • 0 • 0 • •
-----------
D
I C o.o;,., I Cl00.07. ) • C I .DY.I • I 11. 0Y.I • I 0 .07.l • I O.OY.I I • I O.OY.l
0
0
.....
...,
1./'1
STUDY 82S
0077b
PROGRAM: Yeast Recombinant Hepatitis 8 Vaccine, Study 825
PURPOSE: To evaluate antibody and c1tn1cel responses to a high

dose (100 mcg) level of yeast recombinant hepatitis B
vaccine emong adult hemodialysts patients.
VACCINE: Yeast Recombinant Hepat1t1s B V;cc1ne

Lot #1005/C-L915 (100 mcg/ml)
PRIMARY Harvey J. Alter, N.O.

INVESTIGATOR: Chief, Inmunology Section
-~c~DAAY Beverly Elder, R.N.

INVESTIGATOR: Clinical Center Blood Bank
Barry Strauch, M.D.
Fairfax Dialysis Unit
8316 Arlington Blvd.
Fairfax, Virginia 23022
Jaines Shih, Ph.D.
Bethesda, Mary1and 20205
STUDY LOCATION: Fairfax Dialysis Unit

831b Arlington Boulevard
Fairfax, Virginia 23022
Bio-Medical Applications of Annapolis
203 Ridgely Avenue
Annapolis, Maryland 21401
Bio-Medical Applications of Washington
4905 Del Ray Avenue
24751/00871/l
1/19/86
00777
Study 825
STUDY POPULATION: The study population consists of 75 - 100 adult

hemodialysis patients of either sex (excluding
pregnant women) who are negative for HBsAg, anti-HBs,
anti-HBc and who have a nomial ALT. Patients who have
been shown to be nonresponders to three or more doses
of plasma derived vaccine may be e11gible for
participation in the study. Dialysis patients must
not be receiving any innunosuppressive therapy or be
allergic to yeast.

vaccine (100 mcg) on Day 0, 1 and 6 months. Study
subjects are asked to record their te11perature for
five days after each injection and note any local or
systemic complaints.
Blood specimens are obtained prior to vaccination,
monthly for three months and at 6, 9, 12 and 24 months
post initial injection. All specimens are assayed for
ant1-HBs, ant1-H8c, HBsAg and ALT by Dr. Alter.
Samples with an anti-HBs titer ~ 25 11IU/ml may be
tested to determine anti-a and anti-d activity.
Samples 111ay be tested for yeast antibody at MSDRL.
RESULTS: DIALYSIS PATIENTS:

100 mcg flot #1005/C-L915 at 0, 1 and 6 months.
Injection Number
..L _2_ _3_
44 41 0
24751/00871/2
1/19/86
00778
Study 825

participants at 3 months. At that time. 68%
(19/28) seroconverted (S/N ~2.1) while 25% (7/28)
developed protective levels of antibody. The GfrlT
for all vaccinees was 4.4. Table 1 shows
seroconvers ion rates and GMTI s through 3 110nths
of follow-up.
Clinical follow-up data is available for 44 and
39 participants following injections one and two,
respectively. Specific complaints and maximum
temperatures reported during the 5 days f~l lowing
these injections are provided in Tables 2 and 3.
Type of FreouentY tn I b~ In~tion No.

Cmpl&int Dose \.awl ___J__ _,l_ ___L_
Injection 100 acg 9(4144) 8(3/39)

Site
Systellic 100 IIC9 7(3/'4) 0(0/39)
There have been no serious or alarming adverse

ALT Elevations
Three subjects have had elevations of ALT ranging
from 3-5 times the upper limit of nornial. One of
these elevations occurred one 110nth after
receiving the first dose of vaccine, was
transient, and returned to nonnal within a month.
The other two elevations occurred one to two
months after receiving the first dose of vaccine.
Both have remained elevated through three months
of follow-up. No reason for these elevations have
been discovered. The subjects have not shown any
clinical or serologic signs (H8sAg or anti-H8c) of
hepatitis B.
24751/0087/3
1/19/86
007H
Study 825
RESULTS: (Cont.} HBV Markers (ant1-HBc)

Two subjects whose prevacc1nat1on sera were
negative for anti-HBc had one or more positive
serum samples post-vaccination. In the first case
the positive ant1-MBc occurred at 3 months and was
transient. A 4-fllOnth sample was negative for
ant i-HBc. The subject has rema 1ned negative for
ant1-HBc through 6 months and has shown no other
serologic or clinical signs of illness.
In the second case the positive anti-HBc occurred
at 3 110nths. Samp 1es taken at 4 and 6 months
continued to be anti-MBc positive. The patient
has been antt-MBs positive since 3 months. He has
reaiained HBsAg negative and there has been no
report of clinical illness. He continues to be
closely monitored.
Reactions Reported to OoBRR
Case b)(6J a. 31 year old male hemodialysis patient
-with ~~KD, diabetes
mellitus and hypertension,
died b) (61days after
administration of his first
-1,.4.,. .. 4 ,.n of vaccine
(100 mcg Lot 1005/C-L915) on
(b (6) No adverse effects due to vaccination
were noted. The cause of death was reported as
cardiac arrthym1a secondary to end stage renal
disease. The death was not related to vaccine.
case t>)(S) a 73-year-old fe111le, died on (6
from cerebral vascular accident seconaary to
diabetes me111tus associated vascular disease.
She had rece ...... ♦(· - ·-) (... __)__ l 00 me lot
1005/C-L915 on !-r=-.
b 5 . On (b) (6
the patient came or sche<lule<I d alysis. While· on
dialysis, she complained of weakness on her left
side. She was hospitalized until her death on
16) (6) The death is not considered to be
vacc1ne related.
24751/00871/4
l /19/86
Table l
ANTIBODY RESPONSES FOLLOWING VACCINATION WITH RECOHBIHANT HEPATITIS 8 VACCINE
STUDY 0825
POPUUTlON DIALYSIS PATIENTS
DOSE 100 HCG
LOT CL915
REGIMEN O, 1, AHO 6 110NTHS
IHlTIAL SEROLOGY! NEGATIVE
I :( WITH ANTI-HBS I GtlT (SIN) I

1---------------------------------------r-----------------------------------------------------1
I I I RESPONDERS I
TINE
CNONTHS)
1---------------------------------------l-----------------1-----------------------------------I
I S/M >= 2.1 I SIN>• 10 I All VACClN!fS I SIN>= 2.1 I SIN>= 10 I
·······~······-··························
I I I .. ··························································•*••·········
I
I l HOl~TH 1 UX CS/381 I QX C0/38) I 1,3 I 3,0
I I I I 1
I 2 HONTHs I 37X u1t13e1 I 1ex '7/381 I 2.s I 10.2 I 26.9
I I I I I I
I 3 HONTHS I 68)( 1191281 I 1!5)( C7/28) I "·" I 8,'t I 33.3
I I I I I I
.........................................................................·-···········-··························
0
:>
....i
0,
0
Table 2
PATIENT COUNT CLINICAL C011PLA1NTS
RECOt181NlHT HEPATIT~9 8 VACCINE
9TUIJY 0825
TRUTHENT
LOT HUMBER CL915
DOSE I 100 HCG
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACClNU9 ( qq l'ATI£NTSJ • DOSE 1 I
1··-···-··-·····-···-·············-··········-······-················-·······1
I OAYS POST VACCINATIOO I NlltffltR
1··-············-···-···········---·-····-·---·--·····-·---·-·-·-··-··-····-·1
CLINICAL
COHPUINTS
,
...................................I ..........•..........
I
t I 1
I
I 2 I
, 3
......................
I
I 4
......•...
•
• 5 . •
,
..........•..........
I
,
ICOMPllINTS
..........
I •
,
I
MITH
REACTION, LOCAL UHJECT. SITU I 1 I 2 I l I l I l I t I I 4

I I Z.3'O I I 4,5%1 I ( 2.17.1 • I Z.llO I I !.37.1 • ( q,5;0 I I I 9.JXI
·····-·····-
90REM£9S
· -······-·-----·--····•··-···-···•·····-···-1--·-··--·-•-··-···---l-----·-···1·-·-····-·•·-········1··-··-····-
I 1 I 2 I 1 I 1 I l I r I I q
I I Z.llO I I 4,51.1 I I 2.37.1 I I 2.37.1 I I .Z.llO I ( 4.5iO I I I 9.lXI
I I I • I I I I
STIFFHU9/TlGHTNtSS • 1 I 1 I O I t I O I t • I 1
I ( 2.liO I ( 2,37.1 I ( 0.07.1 • I 0.07.1 , I ( t.07.J I I 0,0i"-J I . I I Z.3,O
·········-··-·-··········-···-··-·-•---···--··1--·-······1······-··-1-·-·-··-··1····-·-···1·-·-·····-l····--····1···-······-
sysnHtc I l • ! I 1 I O I O I 1 I I 3
• I Z,3)0 I I 4,51.) I I 2,37.) I I o.o;o I I G.07.1 I ( 2,li"-1 I I ( 6.87.1
----------------------------------------------------------------------------------------------------------------------------
I
WHOL! BOOY/GEH£RAL I 1
Z,3Y.I (
2
~.57.) (
II
O.DZI ( •
o.o;o (
0
0.0Y.I (
•
o.o;o
I
I I
2
4'.5?.)
I
FATIGUE/WEAKNESS I 1 1 0 D 0 0 I l
I. t.liO ( 2.31.) ( O.0lO ( 0. D7. J ( 0 .01.) ( 0.07.1 2.3?.)
I '
I
OTHER I 0
l,Oi"-l (
l
t.37.J (
0
0.07.J ( •
II. 07. J (
0
0.07.1 (
0
o.~;o
I
I '
1
2.3iO
I
RESPIRATORY I 0
0.01.) (
0
0.07.) t
0
11.07.1 l •
0.117.) I •
O.OlO (
1
2. 37.1
I
1I
l
2.37.1
I
PHARYNGITIS (SORE THROAT>
• 0
0.07.J I
0
0.07.) (
0
0,07.J I
0
0.07.J ( •
O.O?.I (
I
Z.JXJ
I I
I I Z.31.J
I
COUGM I 0
o.oin C
0
0.07.) (
0
0.07.) I
0
o. 07.) ( •
0.07.1 C
l
2.37.)
I
I I . Z.31.I
l
I
ltUSCULOSICELETAL I 0
o.o;o (
0
0.07.I (
1
2,S7.I I
0
o.ox, I •
0.07.1 I
0
0.07.1
I
I '
1
2.31.1
I
ARTHRALGil IOTllERI I 0 0 l D 0 II I 1
o.or.1 ( 0 .117.1 ( 2.liO I o.o:o ( 0. D7.1 I o. 07.1 I I 2.37.J
0
...,
0
-
a,
Table 2 (c.:ont.)
PATIENT coun CLINICAL CONPll lNTS
RECOt18IHANT HEPl TIT~S B VACCINE
STUOY t Dll25
Tl!UTI1EMT
LOT NU118ER I CL915
OOSE 100 HCG
PATIEKT CLASS: DI ALYSIS PATI ENTS
I TOTAL YACCIN£ES I 44 PATIENTSt - DOSE l I

Il----------------------------------------------------------------------------1
DAYS POST VACCINATION I NUNBER
CLI NICAL
COt1PLAINTI
l----------------------------------------------------------------------------1
I O I 1 I Z I 3 • 4 • 5 I
MITH
ICOMPLAIHT!I
••••••••••••••••••••••••••••..•••••l••••••••••l••••••••.. •••••••••••l••••••••••l••••••••••l••••••• ..••••••••••••l••a•••••••
-----------------------------------1----------•----------l----------•----------l----------•----------•----------I-----------
PEIISONS MITH COHl'U INT!I I Z • 4 • Z • 1 • 1 • 3 I I 7
I I 4 .5?.t • I 9.1?.t I I 4 ,5i0 I I Z.37.t I I z.1;0 I f 6.97.t I I , 15,<JiO
-----------------------------------•----------•----------•-----
PERSONS MJTlf HO CONPLAINTS I "2 I 40 I
.----•----------l----------1----------1----------1
4Z I 43 I 43 I ltl • I
-----------
37
I c ,s.s,o • c ,o.,;o I c ,s.!Sr.1 I c ,1.11.• I c ,1.r1. t I c ,:s.2;0 t I , att.uo
-----------------------------------1----------
PEllsONS Mlllf HO OATA I e I l----------l----------l----------1·-·-------•----------I----------I-----------
O I O I O I O I O I I o
I I o.o;o I I o. o,o I 1 0.01.1 I I a.or., I I t.oi t I 1 0,07. l I I c 0.01.1
0
...,
0
:J>
"'
Table 2 (cont.)
PATIENT COUNT CLINICAL COffl'LAINTS
AECOt18lNANT HEPATITIS B VACCINE
STUDY 0825
TRU1l1£NT
LOT NU18ER I Cl915
00S! 100 l'tCG
PATIENT CLA!IS: DIALYSIS PATIENTS
I TOTAL VACCINEES ( 41 PATI!HTSI - OOSE t I

l----------------------------------------------------------------------------1
I OATS POST VACCINATION I NUMBER
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------I
• 0 I 1 I Z • J I 4 I 5 I
WITH
ltotU'UINTS
................................... l••·················••l••······••l••······.. •········••l••'"'···············••I••········
REACTION, LDCAl fINJECT, SITU
I
I 1 I
I 1
II 1
I
I l
t
I 1
•
I l
II t
I 3
I C t.6%1 • C t.61.1 I C t.6?.I I C t.67.I I C Z.61.1 I I t.6i0 I I C 7. 7Y.I
-----------------------------------1----------
INflAtt1AllOtC .I O
----------1----------
O I o ----------
o ----------
. o ----------1----------
l I -----------
1
I C 0.07.) C 0.07.J I C 0.01.1 C o.o;o C 0.07.1 I 2.67.1 I C t.6Y.I
I I I
sorn:mss I 1 1 I 1 1 o o I 2
I ( t.67.1 C t.67.1 • C 2.67.1 C t.67.I C 0.01.l I 0,01.l • C 5.llO
I I •
ERYTffEr1A IREOtl£SSI I O O I O O O l I l
I I o.or.1 C a.or., I I 0.01.1 C 0.01.I C 0.0)0 I I
2.6:1.1 C t.61.J
I I I
PRURITIS CITCHIN9 I I D O I D D 1 1 I 1
I I O.DiO C o.o;o I I 0.01.J C O.D1.1 I t.6i0 I Z.6)0 I C 2.61.J
----------------------------------
PERSOHS WITH COttPLAINTS
.1----------1----------1----------1----------•----------•----------•----------•-----------
I l I l I l I l I 1 I 1 I I l
t I 2.61.l • C Z.61.I I I t.61.I I I 2.61.t I I t.61.1 I c 2.61.1 I I c 7. 7Y.I
-----------------------------------1----------•----------1----------1----------1----------1----------1----------1-----------
PERsom MITH HO CCH'UINB I l8 • l8 I 38 t l8 I l8 I l8 • I 36
I c 97.47.1 I c 97.41.J I I 97.41.1 I c 97.47.1 I I 97.47.1 I I 97.4i0 I I C 92.31.J
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS NITlt HO DATA I 1 I l I 1 I 1 I I I 1 I I 1
I I t.SY.I I C t.5)0 • C Z.57.) I I Z.57.) I I t.5)0 I I z.s:o I I C z.s;o
0
...,
0
0,
u,ll
Table 3
PATIENT COUNT NAXI11U11 TEHl't:RAl\JRES
RECOl1BINANT HEPATITIS 8 VACCINE
SlUIIY a112s
TREATNE'NT
LOT Nllt18EII CL91S
DOSE lOG 1'1CG
I TOTAL VACCINEES l 44 PATIENTS) - DOSE l I

1---------------------------------------------------------------------------------------l
I DAYS POST VACCINATIOH I ~ER
HAX Tl~IIAT\11!£ 1---------------------------------------------------------------------------------------I MITH
lDEG F, MALI I O I 1 I Z I 3 I 4 I S •
, I I NAX TEMP
.................................................................... ................................ .......... ....•..... , ,
NOIIHAl I l I l I l l I l I 1 I I l
2.41.) • I 2,7%1 • I z.ttr.t •I 1 2.6)0 I I Z.47.J I l t.eio I I c t.'JX)
I I I I
< 99 I 34 I 31 I •
39 I 31 I 37 I t9 I • I• 27
a1.o,o I I 83,111.J • I 92.97.J I I 81.67.t I I ff,27.t I I eo.t.Y.J I I 1 62.ext
I I I I I
I 7 I • I 2 4 I I• 5 I I 12
99 - 99.9 5
16.T/.) I l 13.5%) I I •
4.87.J I t lD.5%1 I I '
7.3:0 I l U.9Y.I I I c 21.,;o
100 - 100. 9 • o • o I o • 2 · I D I 1 I • :s
I I O.OY.) • I 0,0:0 • I O.OY.) I I 5.3:'.) I I 1.D7.I I I t.117.t I I I 7.DiO
-----------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEHPERATURE TAKEN I "2 I 37 I 42 • 38 I 41 I 36 I I "3
I l 95.SlO I I 84.17.I I I 95.57.) I I 86.47.) I I 93.2)0 I I Ill.SY.) I I I 97.7i0
------------------------l----------l----------l----------l----------l----------l----------l---------------------•-----------
TE11PERATUIIE NOT TAKEN I Z I 7 I Z I 6 I J I a I I . 1
I I 4.51.J I I 15.97.1 I I 4.5l0 I t ll,67.t I I 6.~, I I l&.27.1 I I t 2.37.J
0
0
-4
OIi
.c:
Table 3 (cont.)
PATIENT COUNT HAXIl1Ult TEHPERATURE9
RECott8INAHT HEPATITIS 8 VACCINE
STUDY l 0825
TRUTNENT :
LOT HUHBER I CL915
DOSE : 100 nee
PATIENT CLAS,: DIALYSIS PATIENTS
I TOTAL VACCINfES I 41 PATIENTS) - DOSE 2 I

l---------------------------------------------------------------------------------------1
I . DAYS POST VACCINATION I NU118ER
1I--------------------------------------------------------------------------------------I
"AX TENPERATURE
(DEC F, ORAL!
, I I I I 2 I 3 I 4 I J
, I I
•...•................... ......................................... .............................. .......... ..........
I
I HAXWITH
TEHP
, ,
NOR11Al I I l l ll I l Io
o.o;o 1 2.,:r.1 c 2 .,:1., c 3.o;o I , 2.,:0 t t.9"/.1 I , o.ox1
I I
< 99 I n t9 JO 30 I n 33 I n
71'o.Z7.J I 85.J;CJ l 85.T.0 ( 90.97.) I l 82.9)0 ( M.3:1.) I ( 64.lY.J
I I
99 - 99.9 I 7 ,. 4 2 I s 1 I n
C 22.61.J C 11.e?.) ( 11.47.J C 6.UO I I 14.:SY.I I Z.9"/.J I I 33.37.J
I I
100 - 100.9 I I o o o ·I o o I 1
I C J.21.) I o.o;o ( 0.07.J I 0.07.J I ( 0.07.1 I o.o:o I l 2.67.)
------------------------l----------l----------l----------t---------l----------l----------l---------------------l-----------
n 11Pttt.t.1URE TAKEN I n I 34 I u I 33 I :s5 I 1s I I 39
I I 75.61.1 I I e2 .,x1 I c es.4:t.J I t eo.s;o I t 85. 4 7.1 I l 85.47.1 I I l 95.17.J
------------------------l----------l----------l----------l----------l----------1----------1---------------------I-----------
TEHPERATURE NOT TAKEN I 10 I 7 I , I e I , I 6 I I z
I ( 2.......,0 I C 17.UO I ( 14.6i0 I I 19.SlO I I 14.6:CI I I 14.67. I I I I 4.91.J
0
0
....,
:JI
I.II
Q0
M
GO
►
Q
.:::,
.I-
~
007R6

Study 838.

recombinant hepatitis 8 vaccine in the following,
1nit1a1Jy seronegat1ve. adult populatio~s:
1. Dialysis Patients
2. Predialys1s Patients
PRINCIPAL Professor Dr. Friedrich Deinhardt

INVESTIGATOR: Director
Max v. Pettenkofer Institute
Pettenkoferstr. 9a
8000 Muenchen 2
West Gennany
SECONDARY Dr. Wolfgang J11g

INVESTIGATORS: Max v. Pettenkofer Institute
Pettenkoferstr. 9a
8000 Muenchen 2
West Gennany
Professor Dr. Juergen Bonmer
Hediz1nische Univers1tatsklin1k
Berghe1mer Str. 56
6900 Heidelberg 1
West Gennany
Professor Dr. R• .Mueller
Medizinische Hochschule Hannover
Abt. f. Innere Medizin
Karl-Wiechert-Allee 9
0-3000 Hannover-Kleefeld
West Germany
Professor Dr. Horst Braas
Staedtische Krankenanstalten
Med1z1n1sche K11n1k II
Bremserstr. 79
D-6700 Ludw1gshafen
West Germany
25141/1 .
1/3/86
00787
Study 838
SECONDARY Dr. Bernhard Weinel

INVESTIGATORS: Staedtische Krankenanstalten
(Cont.) Medizinfsche Klinik II
Bremserstr. 79
D-6700 Ludwigshafen
West Gennany
STUDY LOCATIONS: Munich, Heidelberg, Hannover, and Ludwigshafen,

West Gennany
DATE INITIATED: June 7, 1984
STUDY POPULATIONS: Under the original protocol and subsequent addenda ,

the following groups are enrolled in the study.
Participants raay be of either sex, but pregnant women
are excluded. Prospective vaccine recipients must be
negative for hepatitis B sero1og1c raarkers, have a
nonnal ALT level and may not have received any
hepatitis • B vaccine (except as noted under
addendum #2).
Protocol/ Approx.
Addendum# Population Number Regimen
Initial Health Care 25 10 mcg (0.5 ml)
protocol Personnel at 0, 1, and 6
months
Initial Dialysis 50 40 mcg (2 X 1.0
protocol Patients ml) at 0, 1 and
6 months
Add. #1 Dialysis 20 20 mcg (1.0 ml)

Patients at O, 1, 2, 3, 4,
and 6 months
Add. #1 Dialysis 20 40 racg (2 x 1.0 ml)
Patients at 0, 1, 2, 3, 4,
and f> months
25141-2
1/3/86
00788
Study 838
STUDY POPULATIONS: Protocol/ Approx.

(CONT.) Addendum l. Po2ulation Number Re51tmen
Add. #2 Initial 10 mcg (0.5 ml)
protocol for health care
subjects who personnel: 40 111eg
do not fonn (2 x 1.0 ml) for
ant1-HBs dialysis patients
after 3 doses
of vaccine
Add. #3 Predialysis 10 10 mcg (2 x 1.0 ml)
patients at O. 1, and 6
months

STUDY POPULATIONS.
Study participants will be asked to record thetr
temperature for five days after each injection and to
note any local or systemic complaints.
Serum samples will be obtained prior to and on the day
of vacc1nation. Follow-up blood speci1nens will be
obtained 1, 2, 3, 6, B, 12 and 24 months post the
initial injection of vaccine. Nonresponders who
receive a fourth injection of vaccine under addendum
#2 will have a blood sample taken one month after this
injection. Serum samples will be assayed for HBsAg,
antt-HBs , ant1-HBc and ALT by Dr. Deinhardt's
laboratory. Samples may also be assayed at MSDRL for
yeast antibody. ·rhose that are positive for antf-HBs
with a titer of ~25 mIU/ml may be assayed for anti-!
and anti-~ subtype specificity.
25141-3
8/3/86
007M
Study 838
RESULTS: DIALYSIS PATIENTS:

40 mcg Lot #986/C-K733 at 0, 1, 2, 3, 4, and 6 months
20 mcg Lot #9B6/C-K733 at 0, 1, 2, 3, 4, and 6 months
Injection No.
Regimen _1_ _2_ ....L ...!... _s_ ..L
3 x 40 mcg 51 51 48
6 X 40 mcg 20 20 20 19 19 17
6 X 20 mtg 20 20 20 20 20 17
Note: All vaccine was admfnhtered into the

buttock.
2. Sero logic Results:
at 7/8 months who received three 40 l'ICg injections
of vaccine at 0, l, and 6 months. Seroconversion
(S/N >2.1) for anti-H8s at that tinte was 641
( 23/36). Fifty-eight percent ( 21 /36) of the
patients developed protective levels of anti-H8s
(mIU/ml ~10). The GMT at 7/8 months for all
vaccinees was 12.3 mJU/ml and 115.5 for responders
(mIU/ml ~10).
Serology data are available for 15 patients at 10
months who received sfx 40 mcg injections of
vaccine at 0, 1, 2, 3, 4, and 6 months.
Seroconversion (S/N ~2.1) for ant1-HBs at that
time was 671 (10/15). Sixty percent (9/15)
developed protective levels of anti-HBs (m!U/ml
~10). The GMT at ten months for all vaccinees was
6.7 mIU/ml and 21.7 for responders(mIU/ml ~10).
Eighteen subjects who received six 20 mcg
injections of vaccine at 0, 1, 2, 3, 4, and 6
months, have serology data available for the ten
month follow-up interval. Fifty percent (9/18) of
the patients seroconverted for anti.-HBs ( S/N ~2 .1)
25141/4
l /22/86
007«>0
Study 838
RESULTS (CONT.): at that time. Forty-four percent (8/18) developed

protective levels of anti-HBs (mIU/ml ~10). The
GMT at ten months for all vaccinees was 4.7 mIU/ml
and 55.0 for responders(mIU/ml ~10).
Refer to Table 1 for anti-HBs responses and GMTs,

by dose regimen, for other time intervals.

38, 16, and 17 participants after each injection
in ihe 3 x 40 mcg, 6 x 40 mcg, and 6 x 20 mcg dose
regimens, respectively. The overall frequencies
of complaints are presented below.
T:,,,e of F in \ bv Inwtion
ca,plaint Regiasen 1 2
Injection 3 X (0 llltg 0(0/51) 0(0/49)

3
0(0138)
' 5 6
Site 6 X (0 IIICg 0(0/20) 0(0/20) 0(0/20) 0(0/19) 0(0/19) 0(0/16)

6 X 20 IIICQ 0(0/20) 0(0/20) 5(1/20) 0(0/20) 0(0/20) 0(0/17)
Systanic 3 X (0 IICQ 8(4/51) 0(0/49) 3(1138)

6 X 40 mcg 15(3/20) 10(2/20) 15(3/20) 16(3/19) 0(0/19) 0(0/16]
6 X 20 IIICg 5(1/20) 10(2/20) S(l/20) 5(1/20) 0(0/20) 0(0/17]

specific clinical complaints by dose regimen and
injection number. Maximum te,aperature data are
provided in Tables 5 through 7.
HBV M
arkers (Ant1-HBc)
One patient enrol led in the 3 x 40 mcg group was
ant1-HBc positive and had an ALT level approxi11ately
1. 5 times the upper 11m1t of norma 1 prior to
vaccination. He has remained ant1-HBc positive
post-vaccinat;on. Post-vacc1nat\on ALT levels have
not been ascertained. All pre- and post-vaccination
samples were negative for HBsAg. There has been no
report of illness 1n this subject. The patient has
not developed protective levels of anti-HBs (mlU/ml
~10).
25141/5
1/22/86
Study 838
RESULTS (CONT.): A patient in the 3 x 40 mcg group ~as anti-HBc

positive prior to vaccination. In all subsequent
post-vaccination samples, she was negative for
ant i-HBc . The subject deve 1oped prote~t ive 1eve 1s of
ant1-HBs (mIU/ml ~10) at two 1110nths after the second
injection.
A male dialysis patient in the 6 x 20 mcg group became
positive for ant1-HBc one month after the sixth
injection of vaccine. He was HBsAg negative. The
subject had developed protective levels of ant1-HBs
(mIU/ml ~10) at the time of his fourth injection with
a titer of 29 mIU/ml. One month after the sixth
injection his antt-HBs titer was 438 mIU/111. There
has been no report of illness in this patient.
A 70-year old male with a history of coronary artery
disease and end staae _renal disease died of a
myocardial infarction (b} (6) days after receiving the
fifth injection of vaccine (6 x 40 mcg group). H1s
death was not considered to be vaccine related.
A 46-year old male dialysis patient with a history of
diabetes mellitus and diabetic nephropathy, died two
months after administration of his third injection of
vaccine (3 x 40 mcg group). Death was due to cardiac
arrest secondary to hyperkalem1a and was not
considered vaccine related.
PUBLICATIONS: Mueller R, Bonner J, Braas H, Deinhardt A, Jilg W,

Kuttler G, et · al. Erste erfahrungen mit
rekombinanter hepat;tts a-vaccine be1 patienten
unter chronischer haemodialyse-behandlung.
Gastroenterol 1985; 23: 297.
25141/£,
1/22/86
00792
Study 838
RESULTS (CONT.): PREDIALYSIS PATIENTS:

40 mcg Lot #986/C-K733 at 0, l, and 6 months
Injection Ho .
_1_ _z_ ..1
8 e 0
one month serology data are available for all
eight vaccinees. Anti-HBs responses at that time
are sumiarized be low:
- - - - - Gm (mlU/1111) - - - -
- 'I, with Anti-HBS - - - Responders - -
SIN ?;_2. I mlU/11I ?:,ID All Vacctnees Sit:! ?:,2. t
ralU/1111 ?:.10
13(1/8) 0(0/8) 0.7
Clinical follow-up data are available for eight
participants after the first Injection. There
were no c1in1cal complaints or temperature
elevations. · No serious or alarming adverse
reported.
25141/7
l/3/86
Table 1
Antibody RMponses lftDng Dialysis Patients Following Vaccination 1,1ith

Yeast Recmt>lnant Hepatitis 8 Vaccine lot I '96/C-K733 in Study 1838
40 mca at 0. 1. and 6 Months 40 n:a at O 1- 2- 3. 4 and 6 Months• 20 IIICG at O. 1. 2. 3 4 ind 6 flonth~

\ with Anti411s GNT C111IU/■U \ with Anti 411s GNT f•IU/1111' -& with Anti 41Ss GIIT C■IU/ltl>
Resoonders ResDonders Re.,,,,_rs
Tillt! llllU/1111 All 111IU/■l 111IU/111l All IIIU/1111 111IU/111l All mIU/1111
Om.) S~Z.l ~ 10 Vaccinees ~2.1 ~ 10 5~2.1 ~ 10 vaccinees s~2.1 ~ 10 S~Z.1 ~ 10 vaccinees S~2. 1 ~ 10
0 0 0.3 -- - 0 0 0.3 -- -- 0 0 0 .3 -- --
' (0/48) (0/48) (0/20) (0/20) (0/20) (0/20)
2 30
(14146)
13
(6/46)
0.9 --- -- 21
(4/19)
s
(1/19)
0.6 10.0 50.0 15
(3/20)
10
(2/20)
0.5 16.5 25.0
3 3S 22 1.3 16.S 31.0 3S 20 1.2 11.4 33.!, 32 26 1.2 23.6 31.4

(16/46) (10/46) (7120) (4120) (6/19) (S/19)
6 34 29 1.4 26.1 33.B 69 69 32.2 189.8 189.8 56 44 9.1 87.3 190.0

(12/35) {10/35) (11/16) (11/16) (9/16) (1/16)
118 M 58 12.3 90.2 115.5 -- - ---- --- -- - -- --- ---- -------

(23/36) (21/36)
10 65 54 12.8 13.8 117.6 67 60 6.7 24 .S 21.1 so 44 4.7 45.0 ss.o

(24/37) (20/37) (10/15) (9115) (9/18) (8/18)
1rtJose schecllled at 6 111onths IMS actually adllinistered at 5 IIIDftths in lll>St cases.
!«>TE: All injections ..ere i nto the buttock. 0

,::,
~
·D
.....
25141-9
. 1/3186
Table 2
'ATIENT COUNT CLihlC,L C011PLlIHTS
RECOMBINANT HEPATIT 1S B VlCCIHE
STUDY 0838
TR!:ATl1l!HT
LOT NUl1B £R CK733
DOSE 40 11CG *
I TOTAL VlCClHEES I 51 PAllEHTS I - DOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I IM18ER
CLINICAL
CONPLAINTS
.1----------------------------------------------------------------------------I
I o I 1 I 2 I 3 I ~ I 5 I WITH
(C011PLAINTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , •••••••••• , •••••••••• , ••••••••••••••••••••• , •••••••••• , . . . . . . . . . . , ••••••••• ff
-----------------------------------1----------l----------l----------l----------l----------l----------l----------1-----------
sYsrEHIC I 1 I 1 I 1 I 1 I 1 I D I I 4
I I 2.0:0 I ( 2.0;0 I I 2.0;0 I I 2.0;:1 I. ( 2.0;0 I I o.o;o I I I 7.e;o
·-------------------
1 -------------------------------------------------------
I I I
WHOLI! BODY/GEHERAL I l l I 0 0 0 I 0 I ( 2
2. or. 1 , 2. o;oI , o. o;o I o. 01. > , o. 01. > I I o. o:o I I 1 3. 97. 1
I I I I
CHILLS I O l I O O O I O I I 1
0.01.1 , 2.0:0 I , o.o;o I o.oz1 , o.o;o I , 0.01.1 I I , 2.0;:1
I I I I
LIGHTHEADED I 1 0 I O O O I O I I 1
2.0;0 I o.o:o C 0.07.l ( 0.01.1 l 0.01.l I I 0,07.1 I I I 2.07.I
t I I
CARDIOVASCULAR I 0 0 l 0 0 I 0 I I l
o.or.1 , 0.07.1 , 2.or., , o.or.1 1 o.o;o I , o.or.1 I I , 2.0;0
I I I
OTHER I o O 1 D D I o I I 1
o. or. 1 c o. o;o , 2. o7., l o. o;o , o. or. 1 I , o. ox, I I , 2. o;o
I I I
HERVOUS SYSTEM I O O O 1 l I O I I 1
I 0.01.· ( o.o;o l 0.01.l I 2,0?.) ( 2.01.) I I 0,07.) I I I 2,0;0
I I I
YERTIGO/DIZZIHESS I O O O 1 1 I O I I 1
• 1 o.o;c • 1 o.o;o I , o.o;o , 2.0:0 , 2.01.1 I I o.ox> I I , 2.0:0
-----------------------------------1--------·
PERSOHS WITH COt1PLAINTS I 1
-•----------1----------1----------1----------I----------I----------I-----------
• l I l I l I l I O I I 4
• I 2.0Y.I I I t.07.l I I Z.~~I • I t.01.l I I 2.01.1 I I 0.07.1 I I I 1.er.1
-----------------------------------1----------I----------I----
PERSONS WITH HO Cot1PLAINTS I 50 I 50 I --1----------1----------1----------I----------I-----------
I so I i;o I 51 I I ~7
I 1 98.07.J I c 9&.o;:, I , <1e.o:,:1 I 1 9a.ox, I c 9a.o;o I 1100.ox, I I , 92.2x1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH NO DlTA I O I O I O I o I O I O I I o
I I O. 01. l I t O. Oi! l I l O• 07. l I I I. ox I I I O. 07. I I I O. ox) I I I O. 07. I
* Three injection regimen 0

0
~
.0
~
~
Table 2 (cont.)
PATIEHT COUNT CLINICAL COl1PLAIHTS
STUDY 0838
TREATl1EHT
LOT NUM8ER CK733
DOSE qo MCG
PATIEHT CLASS DIALYSIS PATIEN1'9
I TOTAL VACCINEES I Sl PATIENTS) - DOSE 2 I

1----------------------------------------------------------------------------I
1---------------------------------------------~------------------------------I
CLINICAL
COl1PUINTS
...................................,
I O
,
I 1 I
, 2 I
, 3 I
, " I
, 5 I
, , WITH
I COt1PUINT'S
......•... .......... •......... .......... .......... .......... .......... ..........
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH COIIPLAIHTS I O I O I O I O I O I O I I 0
I I 0.0iO I I o.o;o I I 0.01.l I I o.o:o I I 0.0?.) I I o.OXI I I I O.OY.I
-----------------------------------t----------1----------1----------1----------I---·
PERSOOS NITK HO COMPLAINTS I "' l 49 l 119 I 49 I
------1----------1----------1-----------
49 I 49 1 I ""
I (100.0Y.I I 1100.0Y.l I 1100.0X) I 1100.0X) I (100.DY.I I ·1100.0XI I I (100.0XI
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I---
PERSONS NlTlt NO DATA I O I O I o I O I O I O I I .._____
o
_
I I o.ox, I I 0.01.l I 1. D.OXI I I o.o:o I C 0.01.1 I I O.Or.l I I ( O.o:o
0
....D
0
-
Table 2 (cont . )
PATIENT COUNT ClttlICAL Cot1PUINTS
STUDY 0838
TREATMENT
LOT NUl'eER CK733
IJOSE 40 HCG
PATIENT CLASS IJIALYSIS PATI ENTS
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I 48 PATIENTS I • DOSE 3 I
1I ----------------------------------------------------------------------------I
DAYS POST VACCillATIOH I HlJffllER
CLINICAL
COl1PLAUfTS
1I
-------------------------·
o I 1 I
·------------------------------------------------1
I 3 I 4 I 5 I
WITH
ltot1PUINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••••••••~•••••••••••••••l••••••••••I••••••••••••••••••••••••••••••••
------ - ------ - ---------------------1----------l---------- •----------t ----------l----------l----------l------- ---l-----------
svsnMIC I l • 0 I 0 I 0 I 0 I 0 • • . l
I I 2.67.1 I I 0.0Xl I I 0 . 0ZI I I 0.07.1 I I 0.07.1 I I 0.01.1 I I I 2 . 6XI
------------
CARDIOVASCULAR I l I II • 0 • I O O • • 0 • l
2.67.J • C 0.07.1 I ( o.o::o • C I I
11.07.1 0.07.J I I 0.0:1.1I I 2.67.1
I I I I I I
HYPERTENSION • 1 • II I 0 • 0 I 0 I 0 I l
2.6,O I I 0 . 117.J I C 0.01.1 I f 0.01.I I I 0.07.1 I I 0.01.1 I I 2,6)(1
I I • I I I
DIGESTIVE SYSTEM I 1 I 0 I O I O I O I 0 I l
2.6)() I ( 0.0XJ I ( 0 . DXI I C O.0XI I I O.0XI I I o.o;o • I 2.6)( 1
I I I I I I
NAUSEA I l I o • o I O I o I o I 1
I I Z.67.I • I 0.07.J I C 0.0ZI • I 0.01.1 I I 0.01.1 I C O.0iO • I 2.6XI
-----------------------------------1----------l----------l----------l----------l----------l--------- - •----------•-----------
PERSOHS NITH C011PU IHTS • l I O • D I O I 0 I 0 I I 1
. I I 2.61.) I I 0 . 0XI I I 0 . 01.I I C 0.0Y.I I I 0.01. 1 I C 0 . 07.1 I I I 2.67.1
-----------------------------------1
PEIISONS WITH HD COHPUINTS I
----------•----------l----------•----------I----------I----------I----------I-----------
37 • 38 I 38 I 38 I 38 I la • • 37
I I 97.47.J • U00.01.I I noo.01.1 I 1100.0;0 I 1100.01.l • 1100 . 0XI I I C 97.47.I
-----------------------------------1I ----------1----------1----------1----------1----------•----------•----------•-----------
PEIISONS WITH HO DATA D • D I D I 0 I 0 I 0 I • 0
II 0.01. 1 • I 0.07.J II 0 . 07.1 II 1 .07.1 It 0,0XI • I O.DY.I I II 0.07.1
0
0
....
,0
0-
.,
Table 3
PATIENT CCXMT CLINICAL COMPLAINTS
RECotl8mAHT HEPATITIS 8 VACCINE
STUDT 0838
TREATMENT
LOT NUMllER CK733
OOSE 40 tlCG *
PATIENT CLASS DIALYSIS PATIENTS
I TOTAL YACCINEES I Z0 PATIENTS) - DOSE l I

1----------------------------------------------------------------------------I
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------I
I O I l I 2 I '3 I lt I 5 I
WITH
IC011PUIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I•••~••••••
-----------------------------------l----------t----------l----------l----------l----------l----------l----------l--
svsrE111c I 2 I Z I Z I l I Z I l I I .--------
3
I ( 10.0;0 I ( 10.0:1.J I ( 10.0;0 I I 5.0XI I I 10.0XI I ( s.o;o I I I 15.07.)
WHOLE BODY/GENERAL I l 1 l I l 2 1 I I 3
s.o:o ( s.o::o I S. 0Y. I I I 5.0X) I 10.0Y.l I S.0iO I I I 15.0lD
I I
FATIGUE/WEAKNESS I l l l l z l I I 3
S.01.1 ( 5.07.) I 5.07. I ( s.o:o I 10.0iO I S.0iO I I l 15.07.I
CARDIOVASCULAR I l 0 0 0 0 0 I I l
s.ox, 0.07.) o.o:,o 0.0)0 I It 5 . 07.)
Oll\EA I l
(
0
(
0
' 0. 07. I
0
C
0
' 0.0iO
0 I
I I
I 1
0. 07.) ( 0. 01.) o.o:o I 0.OZ) I It s.o;o
tlUSCULOSKELETAL I
5.0XI
0
(
l
' O.0Y.I
l 0
(
0 0 I
I I
I l
0.0)0 ( 5.07.) ( 5.07.1 I 0.0Y.I ( 0.0iO ( 0.OZI I I t 5.07.I
ARTHRALGIA COTHER I I O I l I l I O I O I O I I l
I I 0. 0Y. J I f 5. 0iO I I 5. o:o I I 0. 01. I I t 0. o;o I I 0. oz J I I( 5. 07. I
-----------------------------------l----------l----------t----------1----------l----------1----------I----------I-----------
P£RSOHS NITH Cot1PLAIHTS I Z I 2 I 2 I l I Z I l I I l
I I 10.0;0 I I 10.07.I I I 10.0Y.l I I s.ox, I ( 10.ox, I I s.o:o I I l 15.07.1
--- ·-------------------------------1----------l----------l----------l-------- ·-1----------I----------I----------I-----------
PERSOHS MITH NO COl1PLAIHTS I 18 I 18 I 18 I 19 I UI I 19 I I 17
I I 90. OY. I I ( 90. OX I I I 90. DY. I I I 95. DY.> I I 90. OiO I I 95. oz t I I t 85. o:o
-----------------------------------l----------l----------l----------t----------1----------1----------1----------1-----------
PERSOHS MITH NO DATA I O I. D I O I O I O I O I I o
I t o. 07. > I t o. OlO I 1 o. 07. l I I O. OX l I t o. ox l I I o. oz l I I I O. 07. I
* Six injection regimen

0
....-c
0
....
Table 3 (cont.)
PATIENT COUNT CLitlI:·u COMPLAINTS
RECOl1BINANT HEP.. ! ··. ': ~S 8 VACC I NE
ST\JUY 083&
TREATMENT
LOT tllMBER CK733
DOSE "40 MCG
---------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I 20 PATIENTS) - DOSE 2
....... -----------------------
I
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I t,\JHBER
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------1
I O • 1 I 2 • 3 I 4 • S I
MITH
ICOttPLAJHTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••!••••••••••
-----------------------------------l----------•----------•----------•----------•----------t----------•----------l-----------
srs1en1c I o • 1 I 1 • 2 I o • o I • 2
I I 0.07.1 • C S.07.I I C 5.0ZI • ( 10.0ZI I C 0 . 0%1 I I 0.0ZI I I ( 10.07.l
--------------------------------------------------------------------------------------------------
' • • I I I
.a!OLE BODY/GENERAL I O • l I 1 I 2 I 0 • D I I 2
I I 0.07.1 I t 5,0ZI I C 5.0ZI • I 10.0ZI I I 0.07.1 I I 0.0ZI • • I ·10.0%1
FATIGUE/WEAKNESS
II O I• O
I• l
•I 2
I• 0
•I O
•I •• 2
I c o.o;o I c o.o;o I I s.or.1 I , 10.0:0 I t o.o;o • , o.o;o I • c 10.oz1
• I • I I I I •
HEADACHE I o I l I O I o I o I o • • l
I ( 0.0%1 • I 5.0%1 • I 0.0ZI • ( 0 . 0%1 • ( 0.0% 1 • I 0.0%1 I • I S. 0ZI
-----------------------------------1----------•----------1----------•----------1----------•----------•----------1
PERSONS WITH COMPLAINTS I 0 • l • 1 I 2 • 0 I O I • -----------
2
I ( 0.01.1 I ( 5.0ZI I ( 5.0Y.) • ( 10.0ZI I I 0.0%) • I 0.0%1 • I I 10 . 0ZI
-----------------------------------1----------1----------•----------•----------•----------•----------•----------1
PERSONS WITH NO tot1PUIHTS • 20 • 19 • 19 • 18 • 20 • 20 I • -----------
18
• {100.01.1 • ( 95,0;0 I C 95.0Z) I ( 90 . 01.1 I 1100.0%1 I 1100.Di!I • I I 90.• 0i!I
-----------------------------------•----------•----------1----------1----------1----------1----------1----------
PERSONS WITH NO DATA • 0 I 0 I 0 • 0 • 0 • 0 •
•• -✓ 0
--------
1 1 o.oz1 • 1 o.oz, • 1 0.01.1 • t o.o;o I • o.o;o • , 0.0%1 I • , o.oz1
0
..,
0
..0
CD
.,,,
lab le 3 (cont.)
PATIENT COUNT CLINICAL COl1PLAIHTS
RECOM8IHAHT HEPATITIS 8 VACCINE
STUDY 0838
TREATtlENT
LOT Hllt18ER CK7'3l
oos, 40 tlCG
I TOTAL VACCINEES ( 20 PATIENTS I - DOSE l I

1----------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I Nllt1BER
1--------------------------------------------------------•-------------------I
CLINICAL
tonPLAIHTS
................................... I
, O I l
..........•..........
-----------------------------------1----------l----------
• Z
.......... I
, 3
.......... I 4
,
.......... I 5
..........,I
,WITH
.......... lt011PLAIHTS
l----------l----------l----------l----------l----------l-----------
.......... , ,
sYsTENit I 1 I 1 I z I 3 I z I 1 I I l
I I s . 01.1 I I 5.01.I I ( 10 . 07.1 I ( 15.0Y.I I ( 10.0Y.I I I 5.01.1 I I I 15.07.1
WHOLE BODY/GENERAL 0 l z I l 0 0 I 3
0.01.) t 5.01.) l 10.0:0 ( 5.0iO t 0.0)0 I 0.0l!I I 1 1s.o;o
I
FEVER ITEHP. NOT REPORTED! 0 0 0 1 0 0 I l
0.0)0 I 0.07.I ( 0 . 07.I ( S.0XI I 0.0;'.) 0. 01.1 I I s . o:o
FATIGUE/WEAKNESS 0 0 l 0 0
' 0
I
I 1
0.01. I ( 0.0XI t 0 .oz, 0.01.1 I I 5.0Y.I
HEADACHE
0.0Y.I
0
' l
' S.0iO
0 0 0
' 0
I
1 l
5.o;o o.o;o O. 01.I o.o;o o.o:o ( 5.01.I
0.01.1 t
'
(
D
' 0
' 0 1
ILUIESS, NOS 0 0 l
s.o;o o. 01.) o.o;o 0.01. I I 5.01.)
'
0.07.I ( 0.07.1 ( (
IWSCULOSKELETAL 0 0 l l
' l 0 l
o.o:o o.o;o s.o;o 0.01.1 5.01.1
5 . 01.1 5.01.1
'
I (
'
(
ARTHRALGI A IOTHERI 0 0 l l l 0
' 1
5. 01.) ( 5.0XI 5.0)0 0 . 0)0 5 . 0Y.I
DIGESTIVE SYSTEft
O.OY.I
l
' 0.07.1
0
I
1 1
' 1
' 1
' 3
5 . 01.J I 0.01.I ( s.o:o ( s. o:o ( s.o:o ( 5.01.1 I 15. 01. I
ABD0t1IHAL PAINS/CRAMPS I O I O I l I O I O I O I I l
o.or., I r o.o;o I , s.o:o I t o.o;o I t 0.0;:1 I I o.o;o I I , s.ox1
I I I I I I I
NAUSEA I l I o I o I 1 I 1 I 1 I I z
I I 5.07.1 I I D. 07.l I I 0.01.l I I 5.01.l I ( 5.01.1 I I s.01.1 I I I 10.0;0
-----------------------------------1----------l----------l----------l----------l----------l----------1----------I-----------
PERSONS WITH COt1PlAIHTS I 1 I 1 I 2 I 3 I Z I 1 I I l
I I 5 . 01.) I ( 5.01.I I t 10.01.1 I ( 15.01.1 I I u.o;o I I 5 . 07.1 I I I 15 . 01.1 :::,
0
.....
-0
,0
-
Table 3 (cont.)
PATIENT COUNT CLI~ICAL COMPLAINTS
RECOl1BINANT HEPlTIT!S B VACCINE
STUOY 0838
TRE.I.T11EHT
LOT NUMBER CK733
DOSE 40 MCG
Pl TIEHT CLASS DIALYSIS PATIENTS

•----------------------------------------------------------------------------1
CLINICAL •--------------. -------------------------------------------------------------1 WITH
COt1PLAINTS I 0 I l I Z I l I It • 5 I lC011PUINTS
.............................................. ,H••····••l••······••l••·················••l••······••l••······••I••···~*••·
-----------------------------------•----------l----------l----------1----------1----------1----------I----------I-----------
PERSONS WITH HO CONPLAINTS • 19 · I 19 I 18 I 17 I 18 I 19 I • 17
. I I 95.0iO I I 95.0Y.J I I 90.0in I I 85.0ZI I I 90.o:o I I 95.0%1 I I I 85.0%)
-----------------------------------1----------l----------l----------l----------t----------l----------1----------I-----------
PERSONS MI1" HO DATA I O I O • O I O I O I O • I 11
I I o,o;o I c o.o:o I c o.o;o I 1 0.01., I c 0.0;:1 I ·c 0.0;:1 I I , 11.or.1
0
0
a,
~
0
.,..
Table 3 (cont.)
REC01'18INANT HEPATITIS B VACCINE
STUDY 0838
TREATI1ENT
LOT NUl1BER CK7ll
DOSE 40 HCG
PATIEHT CLASS DIALYSIS PATIENTS
-------------------------------------------------------------~--------------------------------------------------------------
I TOTAL VACCINEES ( 19 PATIENTS! - DOSE 4 f
l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUl'ISER
CLINICAL
CDHPLAINTS
1----------------------------------------------------------------------------I
I D I 1 I 2 I 3 I· 4 I 5 I WITH
ICOHPLAINTS
•••••••••••••••••••••••••••••••••••l•••••••••• l••••••••••l••••••••••l••••••••••l••••••••••l•••••••••• l••••••••••I~•••••••••
-----------------------------------1----------t----------l----------l----------
sYsTEMIC f 1 I O I 1 I 1
l----------l----------f
f l I 2 I
----------l-----------
I 3
I < 5,3ZI I I 0.0XI I < 5.3XI I < 5.liO I I 5,37.1 I < 10.57.1 I I 1 15 . 87. 1
WHOLE BODY/GENERAL I 1 I 0 I l I 1 I 1 I 2 I I 3
5.3ZI I I O.0ZI I ( 5,3;.:1 II 5.liO I( 5.lXI I ( 10.57. 1 I II 15 . 87. I
I I I I I I I
OIILLS I 0 I 0 I 0 I 0 I 0 I 1 I I 1
II D.OZI II 0.0XI I ( 0.0XI I I 0.0XI II 0.0)0 I I s. 1:1.t I I l 5.))(1
I I I I I I I I
FATIGUE/WEAKHESS I l I 0 I l I l I 1 I 1 I I 2
5.3ZI I I 0.0iO I I 5,3;.o I c 5.3ZI I ( 5.3ZI I l 5.37. 1 I I 1 10 .s:o
I I I I I I I
RESPIRATORY I II I 0 I 0 I 0 I II I l I I 1
o . o;o I 1 o.o;o I r 0.0XI II 0 . IIZI I I 0.11;0 I I 5.37.1 I I I S.lZI
COUQt I DI DI DI Of OI 11 I l
I I 0,0ZI I ( 0.0XI I l o . oz1 I ( o.o:o I c o.ozt I l 5.3;o I I c 5.lXI
----------------------------------1
PERSOHS WITH COMPLAINTS I
-------
1
---l----------l----------1----------1----------1----------I----------I
I O I 1 I 1 I ·1 I 2 I I
-----------
l
I I 5,3ZI I l 0.0XI I l S . lXI I f 5.37.1 I f 5.lY.J I I 10 . 57.1 I I l 15.87.1
-----------------------------------t----------t----------t----------l----------f----------1
PERSONS WITH NO CONPLAINTS I 18 I 19 I 18 I 18 I 18 I
----------1----------1-----------
17 I I 16
I I 94 . 7%1 I (100.0i:I I. I '14.7l0 I I 94 . 7?.I I I 94 . 7XI I I 89.SY.I I I ( 84.2Y.J
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PHSOHS WITH NO DATA I 0 I o I o I o I 0 I 0 I I o
. I I 0 . 0:1.1 I I o.0iO I I 0.0;1.1 I l o.o:o I f o.o;o I I o. o;o I I f o. o;o
0
0
-°"
0
·-
Table 3 (cont.)
Sl\lOY 0838
TREATMENT
LOT Nlt18ER CK733
DOSE 40 11CG

1----------------------------------------------------------------------·-----I
I OATS POST VACCINATION I NUl18ER
CLINICAL
COMPU.INTS
1----------------------------------------------------------------------------I
I O I 1 I 2 I 3 I «. • 5 I
WITH
ICOMPLAIHTS
••••••••••••••••••••••••1ttt•••••••••l•••••••••~t•-••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I•~••••••••
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSotlS WITH COl1PLAINTS I O I O • O I O I O I O I • O
I I o.ox1 I l 0,07.I I I 0,07.1 • I 0.07.1 I I 0,07.1 I c o.07.l I I I o.ox1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH NO C011PLAIHTS I 19 • 19 • 19 I 19 I 19 I 19 I I 19
I 1100.01.1 I c100.ox1 I 1100.ox, I 1100.07.1 I c100.oz1 I c100.ox1 I I 1100.ox1
-----------------------------------1--------··-1-------
PERSONS WITH HO DATA I O I _-1----------1----------1----------l----·-----I----------I-----------
o I O I O I O I O I I o
I I o.o:o I I o.ox1 I l o.ox1 I l o.07.1 I c 0.07.1 I 1· o.ox1 I I c o.ox1
0
0
a:
'::>
N
•
Table 3 {cont.)
PATIENT Cll\JHT CLINICAL COt1PLAIHTS
REC0118IHANT HEPATITIS 8 VACCitlE
STUDY 08311
TREATl1ENT
LOT H\Jt18ER CK7'33
DOSE 'tO 11C6
I TOTAL VACCINEES ( 17 PATIENTSJ - DOSE 6 •

1----------------------------------------------------------------------------I
I DAYS POST VACCIHATlOH • NUH8ER
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------•
• 0 • 1 I 2 • 3 • , I 5 •
WITH
I COMPLAINTS
••••••••••••••••••••••••••-•••••••l••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••I••••••••••
-----------------------------------•----------1----------1----------1----------•----------1----------1----------•-----------
PERSONS WITH CONPLAIHTS • 0 I O • 0 I D I D • 0 • I 0
I C 0.07.1 • C 0.07.> • ( 0.07.I I C 0.07.J • C 0.07.J I I 0.07.1 I • I 0.07.I
-----------------------------------•----------1----------1----------1----------1----------1----------1----------1-----------
PERSONS WITH NO COHPLAitlTS I 16 • 16 I 16 . • 16 I 16 • 16 I I 16
I 1100.ox, I 1100.0X) I 1100.07.1 I 1100.0;:1 I (100.0XJ I 1100.DiO I • 1100.0XI
-----------------------------------1----------1----------1----------1----------•----------1----------1----------•-----------
PERSOflS MITH HO DATA I 1 I l I l I 1 I 1 I l I I l .
I I 5.9l0 I C 5.9i0 • c 5.97.1 I C 5.97.1 I I 5.97.1 I I 5.9i0 • I C 5.97.I
0
0
,:,,
0
\,t
!9
Table 4
PATIENT COUHT CLINICAL Cot1PLAINTS
RECOHBIHANT HEPATITIS B VACCINE
STUDY 08J8
TREATMENT
LOT HUt18ER Ck73J
OOSE ZO 1'1CG*
----------------------------------------------------------------------------------------------------------------------------
. I TOTAL VACCINEES ( 20 PATIENTS) - DOSE l I .
l----------------------------------------------------------------------------1
CLINICAL
COtlPLAINTS
l-------------------------~--------------------------------------------------1
I 0 I l I 2 I 3 I It I 5 I WITH
ICDHPLAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••-••l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------1----------l----------l----------l----------1----------l----------l----------l-----------
sYsTEMIC I O I l I O I O I O I l I I l
I t o.o;o I f 5.01.1 I t 0.01.1 I ( o.o:o I ( 0.0iO I I s.o:o I I I 5.01.)
----------------------------------------------------------------------------------------------------
1 I I I I
lo!KOLE BOOT /GEIERU I II l I O I O I O I O I I l
I I O.OlO I 5.111.)I ( 0.01.1 I I 0.01.) I I o.o;o I I 0.Oll I I I 5.o:o
I I I I I I I
FATIGUE/WEAKNESS I O l I O I O I O I O I I l
I I 0.0%) f 5.01.) I ( 0.01.1 I ( 0.01.) I I 0.01.) I I 0.0ll I I ( 5.07.)
I i I I I I I
DIGESTIVE SYSTEM I I O I o I O I O I l I I . l
I ( 0.0Z) f o.o;o I ( 0.01.1 I I 0.0%) I I 0.01.) I l S.0ll I I I 5.07.)
I I I I I I I
DIARRHEA I O O I O I O I O I l I I l
I l 0.01.1 ( 0.0%) I I 0.01.I I I 0.0'1.) I I 0.01.1 I I 5.0l) I I I 5.01.1
-----------------------------------1----------I----------I-
PERSONS WlTH COHPUIHTS I O I l I
.--------t----------1----------1----------1----------I-----------
O I O I O I l I I 1
I 1 0.01.1 I I 5.0%1 I I 0.01.1 I I 0.07.1 I I 0.01.1 I I s.01.1 I I I s.oz1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----
PERSONS WITH NO COHPLAINTS I 20 I 19 I 20 I 20 I 20 I 19 I I
.-----
19
I noo.oz1 I • 95.o:o I 1100.0;0 I 1100.0;:_1 I 11110.01., I 1 95.01.1 I I c 95.or.,
-------------- 7-------------------l----------l----------l----------l----------l----------1----------1----------1-·---------
PERSOHS MITH NO DATA I t I O I II I O I O I O I I n
I I o.oz1 I , 11.or.1 I 1 0.0;:1 I c 0.01., I 1 0.01.1 I 1 0.0;:1 I I , a.ox,
0
:::>
:x,
0
~
-~
Table 4 (cont.)
RECOl1BIHAIIT HEPATITIS B YACCIHE
STUDY 0838
TREAntENT
LOT .uteER CK733
DOSE 20 HCG
• TOTA.L VA.CCIHEES I to PATIENTS) - DOSE t I

•----------------------------------------------------------------------------1
I DAYS POST YA.CCINATIOH I NU1BER
CLINIC AL
COMPLAINTS
1 ----------------------------------------------------------------------------I
I O I 1 I 2 I 3 I It • 5 I WITH
ICOMPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••• l••••••••••••••••••••• I•••••••••••••••••••••••••••••••••••••••••••
-----------------------------------•----------•----------•----------•----------•----------•----------•----------1
SYSTEHIC • 0 • 1 I O • 0 • 1 • 0 • I -----------
2
• I 0.01.1 I ( 5.0?.) I ( 0.0Y.) • ( o.ox, I ( 5.0Y.) • ( 0.01/.) I I I 10 . 0Y.)
---------------
1
WHOLE BOOY/GEHER.ll I O I 1 I o o I O O 1
0.01.I I l 5. 0?.) I ( o. oi, ( O.OX) I ( 0.0lO I o.or., C S. liO
I I I
HEADACHE I O I l O 0 0 0 1
o.or.1 I , s.or.1 < o.o;o I o. or.1 c o.o;r., , o.ox , 1 s . or. ,
I
LIGHTHEADED I 0 I 1 0 0 0 0 1
0. 01.1 I , s.olo < 0.01.1 , o. or.1 , o. o;o , o.o;n , s.o;o
DIGESTIVE SYSTEtt I O I• l O O 1 O Z
o.o;o I , s.o;n < o. or.1 , o.o;o , s.o::o , o. o;o t 10.or. 1
DIARRHEA I O •• 0 0 0 l O 1
o.o;o • 1 o.oio < o.or.1 , o . o;o I s.or.1 , o. o;o I s.or.1
I
NAUSEA • 0 • 1 0 0 0 0 1
I I o.o;o I ( s.or.1 I , o.or.1 , o . o,o , o. or., c o.or.1 I , s . or. 1
-----------------------------------•----------1----------1----------1----------l----------
PERSOHS WITH CDHPUINTS I O I l I O I O I l
•----------•----------•-----------
I O I I 2
I ( 0.01.1 I I s.or.1 • c o.or.1 • 1 o.or., I , s . o,. , I c 0.01.1 I • ( 10.01.1
----------------------------------- Il----------l----------•----------l----------•----------I----------
PERSOH5 MI TH NO CottPLAINTS 20 I 19 I 20 I zo I 19 I 20
I----------I-----------
I I 18
I (100.0Y.) I f 95.0XJ I 1100.01.J I noo.o;o I ( 95.07.J I 1100 . 01.1 I I ( 90.07.1
-----------------------------------1----------l----------•----------I----------I----------I----------
PERSOHS Wint HO 0 ATA I 0 I 0 I 0 I 0 I 0 I 0
I----------I-----------
I I 0
I I 0 . 0XI I ( 0.0ZJ I I 0.07.) I I 0.07.) I I 0. 07.) I I 0.07.1 I I I o.or.1
0
0
0,
0
-
UI
Table 4 (cont.)
ST\JllY 0838
TREATl1EHT
LOT HUl-ltlER CK733
DOSE 20 MCG
I TOTAL VACCINEES C 20 PATIENTS I - DOSE l I

1----------------------------------------------------------------------------I
CLINICAL
COl1PLAIHTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I 3 I - I s I
WITH
ltOHl'UtttTS
•••••••••••••••••••••••••••••••••-1
. I••••••••••1I••••••••••1I••••••••••1I••••••••••1I••••••••••1I••••••••••1I••••••••••1I••••••~•••
REACTION, LOC AL I INJECT. SITE) I l I O I O I O I O I O I I l
I I s.or., I C 0.01.1 I I 0.01.1 I I o.or.1 I l - 0.0%) I I o.or.t I I I 5.0%1
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1----·
PRURITIS IITCHIHG) I l I o I o I o I o I O I I
------
l
1 1 s.or., I c 0 . 01., 1 1 a.or., I c o.or.1 1· c e.ox, 1 1 o.ox1 I I c 5 . ox,
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
svsTEl1IC: I o I o I o I 1 I a I 1 I I 1
I c o.or.1 I I o.ox, I « o.ox, I t s.or.1 I I o.or.1 I t 5 . 0X) I I I s.ox 1
-------------· --------------------------------------------------------------------------------------------------------------
I
WHOl! eooY /GENERAL I O O O l O O I 1
1 o.o;o , o . ox1 c o.o;o I s.ox1 1 o.or.1 1 a.ox, I I s.o;o
I
FATI6UE/WUKHESS I O D D l O O I l
o.or.1 , o.o;o I o.o;o , 5.or.1 , o.or.1 1 o.or.1 I 1 5 . or.,
I
CARDIOVASCULAR I O O O 1 0 0 I 1
0 . 07.1 l o . o;n I 0.07.) I 5 . 0%1 I 0.0%1 ( O.OY.I I I !L0% 1
I
HYPOTEHSI OH I O O O 1 0 0 I l
l o.or.1 l 0.07.) I O.OXI I 5.0Y.I I 0.0%) I O.OY.I I I s.0;1.1
I
DIGESTIVE STSTEn I O O O O O 1 f 1
I 0. OX I I 0. 01. I I O. 01. J I O. 0% l I 0 . 0% I I 5. OX I I I 5. DiO
I
NAUSE A I O O O O O I I l
I , a.oz, 1 o.o;o , o.o:o I , o.or.1 , o.o;o , s.o;o I I , s.o;o
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH COMPLAIHTS I 1 I O I O I l I O I 1 I I 2
f I 5.07.) I I o.o;o I ( a.ox, I ( S . 0%) I ( 0.0%1 I l S.OiO I I C 10 . 0;0
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH NO COMPLAJHTS I 19 I 20 I 20 I 19 I 20 I 19 I I 18
f I 95.07.) I 1100.07.) f UOO.OY.J I ( 95.0)0 I (100.07.1 I I 95.01.1 I I l 90.o;o
-----------------------------------l----------l----------l----------
PERSOHS WITH NO DATA I O I O I O I
l----------l----------1----------I----------I-----------
O I O I O I I 0
f ( o.o;o I I o.o;o I ( o.ax, ·, I 0.0)0 I I O.OXI I I o.o:o I I I o.o;o 0
0
0,
.
0
a-
Table 4 (cont.)
PATIENT COUNT CLINICAL COttPLAIHTS
RECotl8IHAHT HEPATITIS B VACCINE
ST\JOY 08'38
TREATMENT
LOT HUt19£R CK73J
DOSE 20 tlCG
PATIENT CLASS DIALYSIS PATIEMTS
I TOTAL VACCINEES I ZD PATIENTSJ - DOSE 4 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUl'IBER
CLINICAL 1----------------------------------------------------------------------------I WITH
COMPLAIHTS I O I 1 I 2 I 3 I 4 I 5 I ICOIIPLUNTS
••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••••••••••••••I•••••••••••••••••••••
-----------------------------------•----------l----------l----------1----------1----------1----------l----------l-----------
svsrEHIC I l I 1 I 1 I 1 I D I O I I 1
I I 5.0XI I I 5.0XI I I 5.DXI I I 5.0XI I C 0.07.1 I C O.OY.I I I I 5.0XI
I
MHOLE BODY/GENERAL I 0 I 1 I 1 I 0 I D I 0 I I I
O.OXI I I S.OX I I I 5,0XI I I o.or.1 I c 0.01.1 I 1 O.OXI I I I s.or.1
I I I I I I I
FATIGUE/WEAKNESS I • I 1 I 1 I
o.o;o I 1 5.0Y.I I I 5,0Y.I I I
0
o.o;o
I
I ,
0 I 0 I
0.01., I c 0,07.I I
I 1
I I 5. DXl
rt.JSCULOSl(ElETAL
• 5.o;o1
I
I
I
0
I
I
I
0
I
I
0
I
I
I
0
I
I 0
I , o.or.1 I c O.OY.l •• I D.07.) I I 0.07.l I I O.OY.I I
I
I
I
I
I
I
I
(
1
5. OX) .
ARTHRALGIA IOTHERl I l I 0 I 0 I 0 I 0 I 0 I I l
5,o;o I 1 O.OXl I I D. 01. I I I D. 01.1 I t 0.01.1 I I O.OiO I I I 5. OXI
DIGESTIVE SYSTEM I O I O I l I O I O I O I I l
a.ox, II 0.07.l II 5.0XI IC 0.01.1 I( o.o;o II O.OiO I II 5.0%)
I I I I I I I
OIMIHISH(D APPETITE • 0 I 0 I 1 I O I O I O I I I
0.0:1.1 II a.ox, II s.or.1 Ic o.or.1 I, 0.01.1 II o.or.1 I II s.oi:1
I I I I I I I
PSYCHIATRIC/BEHAVIORAL I O I D I O I l I O I O I I 1
I O.OXI I I 0.0%1 I I a.oz, I I 5.0%1 I I 0.07.) I C o.OXI I I I 5.0X)
I I I I I I I
DEPRESSION I O I O I O I 1 I O I O I I I
t , o.ox, I I o.ox1 I , o.o:o I c s.o;o I c 0.0;.1 I I o.or., I I < s.o::o
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsONs WITH COMPLAINTS I l I 1 I I I l I O I O I I l
I I S.OXI I I 5.0iO I I 5.0XI I l 5.0Y.I I l O.o:o I I o.Oll I I I 5.0XI
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsOHs WlTH NO COIIPUINTS I 19 I 19 I 19 I 19 I zo I zo I I 19
I I 95.o;o I I 95.0iO I I 95.0%) I I 95.0iO I 1100.0;0 I U00.07.1 I I C 95.0iO
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSoHs WITH NO DATA I o I o I o I o I o I o I I o
I C 0.07.) I C o.or., I I D.D7.l I I O.Ol) I l O.Oll I I D.0%) I I ( O.OX) 0
0
:,,
...
0
-
Table 4 (cont.)
PATIENT COUNT CLINICAL C0t1PLAINTS
RECot1BlNAHT HEPATITIS B VACCINE
STli>Y 011311
TREATt1ENT
LOT tM18ER CK7l3
DOSE 20 t1CG
PATIENT CLASS: DIALYSIS PATIEHTS
I TOTAL VACCIHEES C 20 PATIENTS) - DOSE S •

1----------------------------------------------------------------------------I
I DAYS POST VACCitlATION , I NU118ER
CLINICAL l----------------------------------------------------------------------------1 MITH
COMPLAINTS I O
, I l
, I 2 I 3 • 1'
, I 5 I ICOHPLAINTS
····-···············.............. .......... ..........•.......... ..........•..........•.......... .......... .........
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
, ,.,
PERSCNs WITH COl1PLAIHTS I o I o • o I o I o I o • I o
I ( 0.07.1 I C 0.07.1 I I 0.0Y.I I C 0.07.1 I C 0.07.1 I I 0.07.1 I I I D.07.1
-----------------------------------1----------l----------t----------l----------l----------l----------l----------l--
PERSONS WITH NO COMPLAINTS I 20 I 20 I 20 I 20 I 20 I 20 I I '-•------
20
I (100.07.1 I U00.07.1 I 1100.07.1 I 1100.07.1 I U00.07.I I (100.07.1 \ I noo.o:o
-----------------------------------1----------1----------1----------1----------1----------1----------•----------1-----------
Pl!RSOHS MITH NO DATA I I I O f O I O f O • • 0 f • 0
I C 0.0Y.I I C 0.07.1 I I 0.07.1 I ( 0.07.1 I I 0.07.1 • I 0.07.1 ,1 I C o.o:o
0
0
OIi
0
a,
-
Table 4 (cont.)
PATIENT COUNT CllNICAL COMPlAIHTS
REC01181NANT HEPATITIS B VACCINE
STUDY 0838
TREATMENT
LOT NUMBER Ck733
DOSE 20 tlCG
------------------------------------------------------------------------------------------------------------------
I
.
TOTAL VACCIHEES ( 17 PATIENTS I - DOSE 6 I ---------
.
1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I t1U11BER
ClINICAL
CotlPLAINTS
l----------------------------------------------------------------------------1
• 0 I 1 • 2 I 3 I 4 I 5 I
WilH
ICOt1PLUNTS
•••••••••••••••••••••••••••••••••••••••••••••• l••••••••••••••••••••• l•••••••••• l••••••••••l•••••••••• l•••••••••• I••••••••••
-----------------------------------1----------I----------I----------I----- -----I----------I----------I----------I-----------
PERSONS WITH COMPLAINTS I O I O I O I O I O I O I I O
I c o.o;o I c o.o;o I c o. o:o I 1 0.01.1 I , 0.01.1 I c 0 . 01.1 I • , . o.ox,
-----------------------------------tI ----------l----------•----------l----------1----------1----------1----------I-----------
PERsONs WITH NO cortP U INTS 17 I 11 I 17.. I 17 I 17 I 17 I I 17
I noo . o;o I noo.OY.I I 1100.oz1 I noo.oz1 I 1100.oz1 I 1100 . oY.1 . I I 1100.0;0
-----------------------------------1----------I----------I----------I----------I----------
PERSDHS MITH HO DATA I 0 I 0 • I I 0 I 0
I----------I----------I-----------
• 0 I I 0
I ( o.o;o I ( o.ox, I I 0.0;() I C o.o;o I I O.OY.I • I O.OY.I • I I 0 , 0Y. )
0
0
~
::,
-D
·-
Table 5
PATIENT COUNT MAXI11U11 TEMPERATURES
RECOf18INANT HEPATITIS B VACCillE
STUDY 08'38
TRE ATMENT
LOT N\Jt18ER
oosr:
CK7l'3
'40 ttCG
*
PATIENT CLASS DIALYSIS PATI ENTS
----------------------------------------------
I
·--------------------------------------------------------------------------
TOTAL VACCIHEES ( Sl PATIENTS) - DOSE l I
----
1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUN8ER
HAX TEMPERATURE
l DEG F, ORALI
1---------------------------------------------------------------------------------------I
I O I 1 I 2 I 3 I 4 I 5 I I I MAXMITH
TEl1P
•••••••••••••••••••••••• l••••••••••l•••••••••• l•••••••••• l•••••••••• l•••••••••• l•••••••••• l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 I 47 I 46 I 48 I 48 I 46 I 43 I I 39
I I 92.ZXJ I I 90.ZiO I ( 94, 1;0 I C 94 . 11.1 I ( 9z,o;o I I 95 . 61.I I I I 76.5?.I
I I I I I I I I ,
99 - 99. 9 I 3 I l I 3 I 1 I 4 I 2 I I . 10
I I 5.9i0 I C 5.91.1 I I 5 . 91.1 I ( 2.01.1 I ( 8.07.I I ( 4.'t1.) I I I 19.61.)
I I I I I I I I
100 - 100. 9 I l I 2 I o I 2 I D I o I I 2
I I 2,0Y.I I I 3.9i0 I I 0.01.1 I I 3.9i0 I ( 0.01.1 I ( 0.01.l I I I · 3.91.1
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TEt1PERATURE UKEN I 51 I 51 I 51 I 51 I so I 45 I I 51
I 1100.01.1 I 1100.01.1 I 1100.01.1 I noo.o;o I ( 98 . DY.) I ( 88.21.1 I I 1100 . 01.1
------------------------1----------1----------I----------I----------I----------I----------I------
TEHPERATURE NOT TAl<EH I O I O I o I O I 1 I 6 I ·--------------1I-----------
0
I I 0.01.1 I I 0.01.1 I I 0.01. 1 I I 0.0;:1 I ( 2 , 0;:1 I ( 11.87.1 I I I 0.07.1
* Three injection regimen
0
0
-
OD
-
Table 5 (cont.)
PATIENT COUNT MAXIl'1\Jl"I TEMPERA~ES
RECOMBINANT HEPATITIS B YACCIHE
STUDY 0838
TREATMENT
LOT NJteER CK733
DOSE 40 MCG

l---------------------------------------------------------------------------------------1
I OATS POST VACCINATION I NUl18ER
MAX TEMPERATURE
tOEGF,ORAll
!-----·---------------------------------------------------------------------------------•
IO • l I Z • 3 • 4 I 5 I •
WITH
•ttAXlEMP
••••••••••••••••••••••••l•••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l•••••••••••••••••••••la•••••••••
I I I I I I I I
< 99 I 46 • 46 I 45 I 42 I 48 I 45 I I 40
I ( 9S.8l'.) I ( 95.8½) I I 9J.8X) I I 87.SiO • (100.0X) I noo.ox, I I ( 83.JX)
I I I I I I I I
99 - 99. 9 I 2 I . z I 3 I 6 I o I o I I 8
IC 4.ZXJ I I lt.:?XI I I 6.3i0 I I U.SXI I I O.OiO I I 0.0?.I I I I 16.?r.J
------------------------l----------•----------1----------1----------1----------I----------I---------------------I-----------
TEMPERATURE TAKEN I 48 I 48 I 48 I 48 I 48 I· 45 I I 48
I ( 94 .17.) I I 94. lX l I I 94 .17. ) I I 94. liO I I 94. 11. l I I e&. 2i0 I • I 94 .17.)
------------------------1----------1----------l----------•----------l----------•----------I---------------------I-----------
TEMPERATURE HOT TAKEH • l • 3 I 3 I 3 I l • 6 I I 3
• ( 5.97.) I C S.9i0 I ( S.97.) • C 5.91.) • ( 5.9?.) I C 11.ex, I I C S.9?.)
0
0
-
0:
-
Table 5 (cont.)
PATIENT COUNT HAXIMUH TEHPERAl\JRES
RECOl18INAHT HEPATITIS 8 VACCINE
STUOf 0838
TP.EATHEHT
LOT NVl18ER Ctc:733
DOSE 40 11CG
I TOTAL VACCIHEES C 48 PATIEHTSI - DOSE l I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION I HUl1BER
1---------------------------------------------------------------------------------------I
HAX TEl1PERATURE
I DEG F, OOAL I • 0
...................................
I
I
I
, 1
.......... I
I
, 2
.......... I
I
, 3
.......... I
I
, 4
.......... I
I
, 5
.......... •
I
, , I
, WITH
.......... I .......... I •...•....•
ttA1< TEl1P
< 99 I 35 I 36 I '38 I 38 I '38 I 38 I I 33

I 1 92,1:io I , 94.71.1 I noo.oio I noo.o;o I 1100.01.1 I 1100.o;n I I I e&.8XI
I I I I I I I I
99 - 99. 9 I 2 I 2 I o I o I o I o I I 4
· I I s.17.J I I s.11.1 I I o.or.J I I o.or.1 I I o.or., I I o.o;o I I c 10.s;n
I I I I I I I I
101 - 101. 9 I 1 I o I o I o I o I o I I 1
I I 2.6lO I I o.o;o • ( 0.01.) I ( 0.DXI I I 0.D1.1 I ( O.OiO I t I 2.67.1
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEHPERAlWE tAKEN I 38 I l8 I 38 I 38 I 38 I 38 I • 38
I c 79.27.1 I l 79.2lO I c 79.27.I I l 79.2ZI I I 79.21.1 I I 79.2i!I I I l 79.2%1
------------------------1----------1----------I----------I----------I----------I----------I---------------------
TEHPERATURE NOT TAKEN I 10 I 10 I 10 I 1D I 10 I 10 I
I-----------
I 10
I I 20.81.l I I 20.8)(1 I I 20.81.l I l 20.81.I I I U.BlO I · l 20.81.l I I I 20.8%l
=>
0
-
(JI
-
IV
Tatile 6
PATIENT COUNT 11AXIMUN TENPERATURES
RECot1BINANT HEPATITIS 8 VACCitlE
STUDT 0838
TRUTnEHT
LOT HUl';BER CK7ll
DOSE 40 t1C6*
I TOTAL VACCINEES ( 20 PATIENTS) - DOSE l I

l---------------------------------------------------------------------------------------1
I OATS POST VACCINATION I HUtlBER
MAX TEMPERATURE
I DEG F, ORAL I
1---------------------------------------------------------------------------------------I
I O I 1 • 2 I 3 I lt I 5 • I I MAXMJTH
TEMP
-····················••l•IHl••·························••l••···~··••l••·····•-1
I I I I I I ••·······•t••·······•
I I••···················
I
< 99 I 11 • 1a I 18 I 11 · I 11 I 1e I I n
I ( 85. ox) • C90. OX I I I 90. OX I I ( 8S. 01. l I I as. OlO I I 'JO. OX) I I I 65. DX)
I I I I I I I I
99 - 99. 9 I 3 I 1 I 1 I 2 I 3 I 1 I I 5
I c 15.0X> I c s.ox1 • c s.o:o I 1 10 . 01.1 I c 1s.o;o I I s.o;o I I , 2s.o?.1
I I I I I I I I
100 - 100. 9 I o I 1 I l I 1 I o I 1 I I 2
I c o . oxi • c s.o:o I , s.01.1 I c s.o;o • c 0.01., I , s .o:o I I r 10 . 0::1.1
------------------------l----------l----------l----------l----------1
TEl1PERAT\JRE TAKEN I 20 • 20 • 20 I 20 I
----------I----------I---------------------
20 • 20 I
I-----------
I 20
I ClOO.OX> I ClO I .OXI • 1100.01.1 I 1100.0?.) • 1100.0X) I Cl00 . 0%1 I I 1100 . 01.1
------------------------l----------•----------1----------1----------
TEMPERATURE NOT TAKEN I O • 0 I O I O I
•----------l----------•---------------------
O I O I
I-----------
I D
I C O.OXJ I C O.OXI I I 0.01.1 I t O. OlO I ( O.OX) I l 0.01.) I I C O.OXI
• Si x injection regimen
0
0
JD
"'
·-
Table 6 (cont.)
PATIENT COUNT HAXIMUtl TEMPERATURES
RECOt1BJNAHT HEPATITIS B VACCINE
STUOY 08la
TREATl1EHT
LOT HUHBEI! CK733
DOSE ltO tlCG
I TOTAL VACCIHEES C 20 PATIENTS) - DOSE 2 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I Nllt18ER
11AX TENPERATUl!E
COEGF,ORALI
1---------------------------------------------------------------------------------------I
IO I 1 I 2 I l I 41 Is. I I
MITH
l11AXTEl1P
••••••••••••••••••••••-1••••••••••1••••••••••1••••••
I I I ·
..••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I
< <19 I 17 I 15 I 16 I 14 I lb I 17 I I 13
I c 89.s;o I c 78.9iO I c ee.97.J I c ez.47.J I c ee.97.J I noo.or.1 I I, 68.4:t.l
I I I I I I I I
99 - 99. 9 I 2 I 3 I l I 3 I
2 I o I I s
I l 10.5l0 J l 1S.8ZI I l S.6i0 I l 17.61.1 I l 11.lXJ I C O.OXI I I l 26.3Y.J
I I I I I I I I
100 - lOG. 9 I o I 1 I l I G I G I o I I 1
I , o.o;o I , s.1;1,1 I l S.6lO I , o.ox, I , o.oY.1 I , o.o;o I I c s.1;0
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TEt1PERATURE TAKEN I 19 I 19 I 18 I 17 I 18 I 17 I I 19
I l 9S,07.J I l 95.0ZJ I l 90.0Xl I l eS.OiO I C 90.0lO I l 85.0XJ I I I '1S.OiO
------------------------l----------l----------l----------l----------l----------t----------l---------------------l-----------
TE11PERATURE NOT TAl<EH I l I l I 2 I l I 2 I . l I I 1
I l 5.0iO I l S.07.1 I t 10.0;:1 I t 15.0iO I t 10.0:0 I l 15.0iO I I l s.o:o
0
0
-
OD
~
-
Table 6 (cont.)
PATIENT COUNT MAXIHUl1 TEMPERATURES
REC0t1BINANT HEPATITIS 8 V.AttmE
ST\IDY 0838
TRUTHENT
LOT NUMBER CK7J3
DOSE <tO MCG
PATIENT CLASS DIALYSIS PATI ENTS
I TOTAL VACCINEES I 20 PATIENTS J - DOSE 3 I

1I ---------------------------------------------------------------------------------------
I
I NU11!ER
1--------------------------------------------------------------------------------------- I WITH
HAX TEMPERATURE
I OE& f, ORAL I
........................,
I
O
,
I
l 2
,
I
l
,
I
4 5
,
I
,
.......... ...•...... .......... .......... .......•.. .......... .......... .......... ,..........
I I I I I I I I
I
I MAX TEHP
,
I
, I .
< 99 I 17 I 16 I l& I l& I 17 I 17 I I 16
I 1 89.s;o I 1 84.2%1 I 1 9't.7%J I 1 94.7%1 I 1 94.1,;1,1 I I' 94 • ._r., I I c &4.2;0
I I I I I I I I
99 - 99 . 9 I 2 I 3 I 1 I 1 I 1 I o I I 2
II 10.5%1 I C 15.&iO I I 5.37. J IC 5 . 37.1 II 5.6%1 II 0.0iO I· II 10.51. 1
I I I I I I I I
100 - 100.9 I o I o I o I o I a I l I I 1
1, o.o;o I c o.ax, I , o.ax, I , o.or.1 I , o.ux, I , s.,x, I I , s.31.1
------------------------l----------1----------l----------l----------l----------l----------l---------------------
1Et1PERATURE T AKEN I 19 I 19 I 19 I 19 I 18 I 1& I
l-----------
I 19
I 1 95.0%I I I 9S.O%J I I 95.0%) I I 95.o;o I I 90.0%1 I I 90.0%J I I I 95.01.J
------------------------ Il----------l----------l----------
TEMPERATURE NOT TAKEN 1 I l I l
l----------l----------1----------1---------------------I-----------
I l I 2 I 2 I I l
I I s.o;o I I s.oz , I c 5.az1 I I 5.0%1 I I 10.0;1,1 I I 10.or.1 I I I s.o;o
0
0
-
0,
·-
I.fl
Table 6 (cont.)
PATIENT COUNT MAXIl'1Utt TEMPERATURES
RECOMeINAHT HEPATITIS B VACCitlE
STUDY 0838
TREATMENT
LOT tMIBER CK733
DOSE 40 t1CG
PATIENT CUSS DIALYSIS PATI ENTS

l---------------------------------------------------------------------------------------1
11AX TENPERATURE
f D[G f, ORAL l
f---------------------------------------------------------------------------------------1
I O I l I 2 I l I 4 I 5 I I
WITH
I NAX TEMP
•••••••••••••••••••••,..• l••••••••••l•••••••••• l•••••••••••••••••••••l•••••••••• l•••••••••• l••••••••••l•••••••••• I••••••••••
• • I I • I I . I
< 99 I 1e I u I 18 I 15 I 16 I 17 I I 15
I I
1100,or.1 I
c 88,9Y.> I
uoo.or.1 I
I 83,3?.I I I I 83,JiO
I 88,9?.l • I 94.4i0
I I I I I I I I
99 - 99. 9 I o I z I o I 3 I 2 I l • I l
I I O,DlO I I 1 1.lY.I I I o.or.1 I I 1(,.7?.I I I 11.1::0 I I 5.6i0 I • I 16 . 7¼)
------------------------l----------l----------l----------l----------l----------1
TEMPERATURE TAKEN I 18 I 18 I 18 I 18 I 18 I----------1--------------------- 18 I I-----------
I 18
If 94.T/.I If 94 , 7XI I ( 94.7¼) I I 94.7)0 I I 94.7") I I 94 . 77.l I I I 94.7¼1
------------------------l----------l----------l----------l----------l----------l----------l---------------------
1E11PERATURE NOT TAKEN I l • l I l I 1 I 1 I l •
l-----------
I 1
I I 5.3Y.I I I 5.3½1 I ( 5,3l0 I I 5 . 3"/.I I I 5.37.1 1. I 5.37.I I I 1 5 . 3::o
0
0
...
0D
0-
Table 6 (cont.)
PATIENT COUNT 11AXJl1Ut1 TEl1PERAT\JRES
RECOt1BIHANT HEPATITIS B VACCINE
STUDY OBJ8
TREATMENT
LOT HUl18ER CK7JJ
DOSE 40 t1CG
PATIENT CLASS OJALYSl9 PATIENTS
I TOTAL VACCJHEES I 19 PATIENTS! - DOSES I

1·--------------------------------------------------------------------------------------1
I . DAYS POST VACCIN.I.TIOH I NUMBER
~AX TENPERATURE
COEG F, ORALI
1---------------------------------------------------------------------------------------I
I O I 1 I 2 I 3 I 4 I S I I
WITH
I 11Al< TEMP
.... ••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
. I I I I I I I I
< 99 I 16 I 16 I 17 I 11 I 17 I 11 I I 16
I 1 94 . 11.1 I 1 88.9Y.l I 1100.01.1 I 1100.or.1 I 1100.or.1 I 1100.or.1 I I 1 8a . ,x1
I I I I I I I I
99 - 99. 9 I o I 1 I o I o I a I a I I 1
I C O.OY.I I I 5.6Y.I I ( O.OY.I I I a.or., I I o.or.1 I I O.OY.I f I I 5.&?.I
I I I I I I I I
100 - 100. 9 I 1 I 1 I o I o I o I o I I 1
I I s. 9Y.> I I s.6Y.l I , o.o;o I , o.o,o I , a.or., I , 0.01.1 I I I s.6;o
------------------------1----------1----------I----------I----------I----------I ·---------l---------------------l-----------
lE11PEAAT\RE TAUH I 17 I l& I 17 I 17 I 17 I 17 I I 18
I ( 89.57.l I I 94. 7?.l I ( 89.SlO I I 89.SXI I I 89.SY.l I I 89.5?.I I I I 94. 71.I
------------------------l----------l----------l----------l----------l----------l----------1---------------------1
TEHPERATIRE NOT TAKEN I 2 I 1 I 2 I 2 I 2 I 2 I I
-----------
1
I I ID.SY.I I I 5.liO I I 10.51.1 I I 10.s;o I ( 10.Si!I I I 10.SY.I I I I S.lY.1
0
0
-
0,
-
Table 6 (cont.)
PATIENT Cotffl HAXIt1Ut1 TEHPERATURES
RECOHSIHAHT HEPATITIS 8 VACCIHe
STUOY 0838
TREATl1EHT
LOT tU18£R CK733
DOSE 40 HCG
PATUHT CLASS DIALYSI S PATIENTS
• TOTAL VACCINEES ( 17 PATIEHTSJ - DOSE 6 I

•---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUt1BER
NAX TEHPERATURE
I DEG F , ORAL I
1
I
----------------------------------------------------------------------------•----------I
O I l I 2 • 3 I 4 I 5 I I
MITK
I HAX TEMP
••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l•••••••••• l••••••••••l•-•••••••l•••••••••• I••••••••••
• I I I I I I I
< 99 I 13 I 14t I u I 14 I 14 I 14 I I 13
I ( e6.7i0 I ( 93.3)0 I UOG.OY.) I I 93.3?.l I I 93 . 3X) I (100 . 0X) I I I 86.7i0
I • I I I I I I
99 - 99 . 9 • 1 I o I o I l I l I o I I 1
I I 6. 7)0 I C O. o:o I C O. o:o I I 6. 7X 1 I I 6. 77.1 I ( 0 . 0)0 I I C 6. 7X I
I I I I I I I I
10a - 100. 9 I 1 I l I o I o I o I o I I l
I I 6.T/.) I ( 6.?Y.! I I 0.0,:1 I I 0.0?.l I I O.OXI IC 0.0?.) I I I 6.7?. I
------------------------1
TEHPERATURE TAkEH I----------1----------1----------1----------1----------l'----------1---------------------1-----------
15 I 15 I 15 I 15 I 15 I lit I. I 15
I 1 88.ZY.t I c ee.2,:1 I c M.2,:1 I , ea.2,:1 I I ee.2r.1 I , e2 . 1t:o I I c ee.2r.1
------------------------I----------I----------I----------I----------I---------- I----------I--------------------- I-----------
TEl1PERATURE NOT TAKEN I Z I 2 I 2 I Z I Z I 3 I I 2
I , 11.e,:1 I c 11.er.1 I , 11 . e;o I , 11.ex, I 1 11.er., I c 11 . 6r.1 I I , 11.er.,
0
0
-
OD
-
:lD
Table 7
PATIENT COUNT HAXlttUf TEHPERAT~ES
RECOHllIIIAHT HEPATITIS 8 VACCINE
SruDY 0838
TRUTt1ENT
LOT HUHDER CK7ll *
DOSE 20 MCG

1---------------------------------------------------------------------------------------
I DAYS POST VACCINATION
I
I taJl1BER
MAX TEHPERATURE 1---------------------------------------------------------------------------------------I MITH
(DEG F , Ol1Al ) I O I 1 I 2 I 3 I 4 I- 5 I I I MAX TEMP
•••••••••••••••••-•••••l••-
I
••••••l••••••••••l••••••••••
I I
l••••••-••1
I I
••••••••••1
I
•••••••••• 1••••••••••1
I
•••••-•••I••••••••••
I
< 99 I 1s I u. I 16 I 17 I 17 I 16 I I 14
I c 83.JY.l I I 88.9:t.) I t 88.9:f.l I < 94.4:f.l I < 94.4i!I I c ea.9;o I I 1 77.6½1
I I I I I I I I
99 - .,, • 9 l I I t I 2 I l I 1 I l I I :,
I l 16.7:!I I I 11.lY.l I I 11.17.1 I I 5.6lO I I 5.6iO I c 5.67.1 I I c 16.7%1
I I I I I I I I
100 - 100 . 9 I o I o I o I o I o I 1 I I 1
I 1 0.07.l I I o.o:o I t 0.01.1 I I o.o:o I I o.o;o I 1 5.67.> I I I s . 67.l
------------------------ l----------l----------l----------l----------l----------l----------1---------------------1-----------
TEHPERATURE TAl< EN I 18 I 18 I 18 I 18 I 18 I 18 I I 18
I t 90.0:t.l I I 90.0:0 I I 90.o:o I < 90.0:0 I < 90 . o:o I c 90 . 07.l I I t 9o.o;o
------------------------1----------1----------I----------I----------I----------I----------I---------------------I-----------
TEMPERATURE HOT TAKEN I 2 I Z I 2 I 2 I 2 I 2 I I t
I c 10.0:r., I 1 10.0:0 I I 10 . 0;0 I t 10.0;0 I I 10 . 0;0 I t 10.0:0 I I c 10.0;0
0
0
-
~
.0
-
Table 7 (cont.)
PATIENT COUNT HAXIHUlt TEHPERAT~ES
RECOl1BINANT HEPATITIS B VACCINE
STUDY 0838
TRUTI1ENT
LOT NUlfl!ER CK 731
DOSE 20 tlCG
PATIENT CLASS D1ALYS19 PATIENTS
I TOTAL VACCINEES I 20 PATIENTSI - DOSE 2 I

•---·-----·····-·-···········--·-·---·-·-·-···--··-····---····-·------··--·----···------1
I DAYS POST VACCINATION I tM18ER
"AX TEMPERATURE •·--·-·-·-····-····-·----------------·-·--·-----··-····-···---·-······-·-·-·····--·-···-1 WlTH
(DEG F, ORAL I • 0 I 1 • 2 • 3 I 4 • S • • • 11AX TEMP
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••-1••••••••••••••••••••••••••••••••
I I I I I • I I
< 99 I 18I 19 I· 19 I 18 I 19 I 19 I • 1a
• , 94.TI.> I noo.o;o I uoo.o;o • uoo.o;o I 1100.0:1.1 I noo.o,o I I , <11t. n1
I I I I I I • •
99 - 99.9 I l I o I o I o I o I o I I 1
I , 5.3:t.l I , 0.0:1.1 • , o.o;o I < 0.0:1.1 I , 0.0:1.1 I < o.or.) 1. I , 5.3r.l
-·····-·---······-·-·-··1-····-····1·········-•··---···--•-----·-·--1·-----·-··1------·---•---·----------·-·----•···--··---·
TEHPERATURE TAKEN I 1' . I 19 I 1" I 18 I 19 I 19 I I 19
I ( 95.0)() I ( 95.0Y.l I ( 95.0Y.I I ( 90.0XI I ( 95.0)(1 I ( 95.0)(1 I I I 95.0iO
··--·-·---·-····-·······1----·-···-1-------·--•--·-······•-----·----l------·---l-------··-1----·-···----·-------l·------··--
TEl1PERATURE NOT TAKEH I l I l • 1 I 2 I 1 • 1 • • l
I I s.o:t.l I c s.o;r.1 I ( 5.0Y.I I I 10.0Y.I I ( s.o;o • I s.o;r.1 • I I s.or.1
0
0
Oil
rv
0
·-
Table 7 (cont.)
PATIENT COUHT 11AXIH\Jt1 TEMPERATURES
STUDY DBl8
TRE ATMENT
LOT H\Jl18ER CK73J
DOSE 20 11cc;
I TOTAL VACCIHEES I to PATIENTS) - DOS£ 3 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I NU118ER
nAX TEMPERATURE
(DEG F • ORAL I
1
I
---------------------------------------------------------------------------------------I
O I 1 I 2 I 3 I 4 I 5 • I
MITH
• MAX 1Et1P
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l•••••••••• l•••••••••• l••••••••••l••••••••••l•••••••••• I••••••••••
• I I I I I I I
< 99 I 1 11 I 19 I 17 I 19 I 19 I 19 I I 15
I C 90. o;: I I C 95. O?. I I I es. 07.1 I C 95. 07. I I C 95. or. I f I 95 . ox I I I I 75. 07. J
I I I I I I I I
99 - 99 . 9 I 2 I 1 I l I 1 I 1 I 1 I I s
I c 10.ox, I I s.o;n I I u.o;o I c s . o;o I c 5.ox1 I I s.ox1 I I 1 25.07.1
------------------------1----------1
TEt1PERATURE TAKEH I to I
----------1----------1----------1
20 I 20 I 20 I
----------1----------1---------------------1---·
U I to I I
-------
20
I c100.ox> I 1100.or.1 I 1100.or.t I 1100.or.t I 1100.011 I 1100.01.1 I I 1100.ox,
------------------------l----------
TEtfPERATURE HOT TAKEN I O
l----------l----------l----------l----------1----------1---------------------I-----------
I O I O I O I O I O I I 0
I c o.o;o I 1 1.or.1 I I o.ar.t I c o.or.» I I o.ox, I I o.ox, I I c o . ox>
0
0
a,
1\1
-
Table 7 (cont.)
PATIENT COUHT MAXIltJH TEHPERATURES
STUDY I 0838
TRE ATtlENT
LOT HUMBER I CK733
DOSE 20 ttCG
• TOTAL VACCIHEES I 20 PAT IENTS> - DOSE 4 I

1--------------------------------------------------------------------------------------- t
MAX TEMPERATURE
I DEG F , ORAL I
f---------------------------------------------------------------------------------------1
I O I l I 2 I l • 4 I 5 I I
WITH
I MAX TE11P
••••••••••••••••••••••••l•o•••••••••••••••••• l•••••••••• l•••••••••••••••••••••l•••••••••• l•••••••••• l•••••••••• I••••••••••
I • I I • I I I
< 99 I 19 • 19 • 19 I 18 I 20 I 20 I I 16
• I 95.07.J • t 95.07.> I I 95.o;o I I 90.07.J I uoo.or.1 I 1100.or.1 I I c 80.07.I
I • I I I I I I
n - 99. 9 I l I o I l I Z I o I o I I 3
I I 5. 01. J I C O•o;o I I 5. ox> I I 10. 07.1 • C o. OX l I I O• o;o I I C 15. 07. 1
I I I I I I I I
100 - 100. 9 I o I l I o I o I o I o I I 1
IC o.07.1 I I 5,0XI It o.or.1 I t o.07.1 I I o.or.1 I I o.or.1 I I c 5.07.l
------------------------l----------l----------l----------1---------- I----------I----------I---------------------I-----------
TEt1PERAn.lE TAKEN I 20 I 20 • 20 I 20 I 20 I 20 I I 20
I 1100 . 0)n I (100.0)() I 1100,07.I I (100.01.1 I (100 . 0)() I 11 00.07.1 I I noo . o;o
------------------------l---------- l----------1----------t---------- l----------1----------I--------------------- I-----------
TEl1PERATURE NOT TAKEN I O I O I II I II I O f O I I 0
I I 0.0)0 • I O. Oi!I I I 0.07.1 I I 0.0)() I I O.Oi!) I l 0.07.1 I I C 0 . 07.)
0
0
-31
rv
- rv
Table 7 (cont.)
PATIENT CO\JHT HAXIl1Ul1. TEHPERAl\JIIES
RECOt1BIHAHT HEPATITIS 8 VACCINE
STUDY I 0838
TRUTitENT
LOT NUl18ER CK733
DOSE 20 t1CG
PATIENT CLASS: DIALYSIS PATIEHTS

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I HUMBER
NAX TEHPERATURE
I DEG F • ORAL I
l--------~------------------------------------------------------------------------------1
I O • 1 I 2 • 3 I '+ • 5 I I
WITH
I HAX TEHP
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••--
1 I I I I I I I
< 99 I 20 I 20 I 19 I 20 I 20 • 20 I I 19
I 1100.0:0 • (100.0Y.J I f 95.0Y.J I 1100.0Y.J • UOO.OY.1 · I UOt.OY.I I I C 95.o;o
I I I I I I I I
99 - 99. 9 I o I o I 1 I o I o I o I I 1
I I o.ox, I I o.ox, I c s.ox> I I o.or.1 I c o.ox> I c o.o;,o I I I s.o:o
----------- .------------l----------l----------l----------l----------l----------1----------1---------------------•-----------
TEHPERAl\JRE TAKEN I 20 I to I to I 20 I 20 I 20 I I 20
I ClOO.OY.) I (100,0Y.J I (100.0lO I UOO.OY.) I uoo.o;o I 1100.0;0 • I 1100.0;0
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TEHPERA1\JRE HOT TAKEN I O I O I O I o I o I. o I I O
I c o.ox, I c o.oY.1 I c o.oY.J I I o.or., I f o.oY.1 I c o.oY.1 I I I o.or.1
:::,
0
OIi
N
\,-1
-
Table 7 (cont.)
PATIENT COUNT HAXIl1ltt TEMPERATURES
REC0l18INANT HEPATITIS B VACCINE
ST\JDY one
TREATMENT
LOT NUtlBER CK733
DOSE zo t1C6
PATIENT CUSS DIALYSIS PATIENTS
-----------. ----------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES C 17 PATIENTS! - DOSE 6 I
l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I tM'IBER
l---------------------------------------------------------------------------------------1
HAX TEHPERATURE
CDEG F, ORAL I I O
...................................
I
,I
I l
,I
.......... I..........
2 I l
,I ,I
.......... I..........
4
,I
I 5
,I , ,I WITH
.......... I.......... I.......... I.......•..
HAX TEHP
< 99 I 1s I 1s I 16 I 16 I 16 I 1s I I u
I « 93.81.J I I 93.81.1 I uoo.01.1 I uoo.01., I uoo.oz, I « 93.&i!J I I t 81.3:t.l
I I I I I I I I
99 - 99. 9 I 1 I 1 I o I o I o I l I I 3
I , 6.31.1 I « 6.3lO I 1 0.01.1 I 1 0.01., I I o.o;o I « 6.3,O I I , 18.e:o
------------------------l----------l----------l----------l----------l----------1----------1---------------------I----------- ·
TEHPERATURE TAJ<EN I 16 I 16 I 16 I 16 I 16 I 16 I I 16
I ( 94.1;0 I ( 94.li!) I I 94.li!I I I 94.liO I I 94.llO I I 94.11.) I I t 94.li!I
------------------------1---------1----------I----------I----------I--------- .l----------1---------------------1-----------
TEMPERATURE HOT TAKEN I 1 I l I 1 I 1 I 1 I l I I 1
I c 5.97.1 I « 5.91.1 I c 5.91.J I c 5.9:t.J I 1 5.9:t.l I I 5.9i!I I I 1 5.97.1
0
0
CD
IV
8::
---
00825
Erste Erfahrungen mil rekombinanter Hepa-

titis 8-Vaccine bei Palienlen unter chroni-
scher H~emodialyse-Behandlung. ·
R. Miillcr', J. Bommer-', J-{. Brus', F. Dcinh:irdt',

A. l'cucrh:akc' W, Jili;', G. Kiinkr', 3. Wci~cl',
Abtcilung iur G;isuocntc:roloi;ic und Hcpatolo-
i;ic, Mcdizinischc Ho.:hs.:_hulc Hannover'; Sck-
cion Ncphroloi;ic, ~lc,fainischc K!inik Univcrsi-
tit Heidelberg'; Mcdi~inischc Klinik It, SciJc.
Krankcn3nn;ihcn LuJ..,ii;shafcn'; M:uc ,·on Pcr-
tcnkofcr lnHituc dcr Ludwii;-i\faximili:an-Uni,·cr-
sit:i.t Miim:h..-n'.
Die lmmuno!:cniuc n:niirlichcr, :au:. Hum;inpl;u-

ma i;c,.,·onncnc:r Hcp:atitij 8-V:accinc lut sich bci
cndogcn odcr cxogcn immunsupprimic:rtcn P:a-
cicntcn beuichdich sc.hwichcr crwiescn a.ls bci •
gaunden Personcn. Es cnchicn dahcr intcmsanc
zu priifcn, ob nach lmpfung mic cincr gcntcchno-
logisch g"-'onncncn HB-Vaccinc bei c:hronischcn
Hacmodi:alysc-Paticntcn hohcrc Scronkonvcr-
sionsr:atcn fiir anci-HB, cniclc wcrdcn konncn als
mit n:atiirlichcm HB-lmpfstoff. 51 HBV cmpfing-
liche P:aticntcn untcr chronischcr Hacmodiilysc•
Bchandlung crhiclccn ) lmpfun~n mic jc 40 ug
Hb,Ag Protein, das in cincm DNS-rckombinicr-
tem Summ der Hcfc Sacduromyca ctt0.-isiac
hcrgcmllr wurdc (Hcpariris B-V:accine {recombi-
nant] MSD. Wcstpoinr USA; Lot 9l4/C-J62S): '
Die zwcitc und drittc lmpfung ttfolgun cinen
bzw. 6 Mon:arc ruch dcr crstcn [mpfung. Eincn
Mon:at n:ach dcr 2. [mpfung hattcn 20 von ~8
(-'2%) dcr P:aticnrcn :anti-HB, gcbildet. Der mitt-
lcrc Antikorper-Cdtalr bcu-ug 2'4,7 [U/ml. Bci 21
Puicnrcn isr du lmpfprognmm a1,scschloucn, 13
\'On ihMn wi.:sen im 7. Monat n:ach lmpfbcsinn
cine Scrokonversion n:ich :inci-HB, auf. Der mitt•
lcrc .inri-HB,-Gc:halt war_auf 151 [U/ml mgaric-
gen. Oana.:h lusen sich bci Dialy:sc-Pacientcn mi,
rckombinat hcrgcuelltcr HB-V:accinc :ihnlichc ~-
rokonvcnions~rcn c~iclcn wie mit HB-lmpf-
sco(f, der :aus Hum:anpl:asma gcwonncn wurde.
COPYRJGHT ~S
DEMETER VERLAG ,
D-8032 GRAFELFIN F£
Huller R, :Bommer J, Brass H, Deinhardt A, Jilg W, Kuttler G, et al.

Erste erfahrungen mit rekombinanter hepatitis B-vaccine be~
patienten unter chronischer haemodialyse-behandlung. Gastroenterol
1985; 23:297.
00626
NOTE: The 1s no 1111ss1ng ater11i. There W&S

an· eM"Or 1n number1 ng.
L
..
REPORT NO. 3
in Support for a License Application for
RECOMBIVAX
Recombinant Hepatitis 8 Vaccine, MSD)
I
CLINICAL DATA*
VOLUME 3 OF 3
F
MENTALLY RETARDED
00827
SUPfflARY - MENTALLY RETARDED INDIVIDUALS
Two studies (Study 815 and 889) are being conducted to evaluate antibody and
clinical responses to yeast recombinant hepatitis B vaccine among
institutionalized mentally retarded individuals who are negative for hepatitis
B virus sero1og1c markers. l\'lentally retarded individuals receive three 10 or
20 11eg doses of yeast recombinant vaccine (Study 815 and 889) or three 20 mcg
doses of plasma-derived vaccine (Study 815) at o. 1. and 6 months.
A total of 200 mentally retarded individuals have conipleted a three injection
regimen of vaccination. · No serious or alamlng adverse reactions attributable
to vaccine have been reported.
Serologic data after one injection of vaccine are available for 201
ind1v1duals. At one 110nth 19-20i of vaccine recipients who received either
one 10 or 20 mcg dose had detectable antibody (S/N ~2.1). Titers of at least
10 mIU/ml occurred in 8% (10 mcg dose) and 11 % (20 nttg dose) of vaccine
recipients at this till!. Among nienta 1ly retarded individuals with a minimum
titer of S/N ~2.1. the geometric mean titers were 8.7 mIU/ml (10 mcg dose) and
13.7 mlU/ml (20 mcg dose). Geometric mean titers for responders with antibody
levels of mIU/ml ?:,10 were 19.9 mIU/ml (10 mcg dose) and 38. 7 mIU/111 (20 rncg
dose}.
Clinical data are available on 201 mentally retarded individuals after two
injections of vaccine . The vaccine has been very 111ell tolerated 1n this
population with very few clinical collll)la1nts reported. No injection site
reactions were reported following either the first or second injection.
Systemic coniplaints were reported in 2% of vaccine recipients following the
initial 10 mcg dose and 1% vaccine recipients following the initial 20 mcg
dose of vaccine. o systemic complaints were reported after the second
injection.
31721/1
1/11 /86
00828
~ENTALLY RETARDED INDIVIDUALS
Study 815 - The Netherlands - Dr. S. Schalm

The study population consists of institutionalized mentally retarded
1ndividuals and health care personnel. Mentally retarded individuals and
health care personnel receive either three 10 or 20 mcg doses of yeast
recombinant hepatitis B vaccine lot 993/C-K937 or three 20 mcg doses of
plasma-derived vaccine lot 22771( at 0, 1, and 6 months. Vaccination and
clinical follow-up continues in progress.
Study 889 - St. Louis , MO - Or. R. Perr11lo

The study populatfon consists of institutionalized mentally retarded
individuals and health care personnel. Mentally retarded individuals receive
three 10 or 20 mcg doses of yeast recombinant hepatitis B vaccine lot
993/C-K937 at 0, 1, and 6 months. Health care personnel receive 10 11eg doses
of vaccine according to the same regimen.
One hundred mentally retarded indivfduals have received three 10 mcg doses of
vaccine. At one 110nth 19% (19/101) participants seroconverted (S/N ~2.1) and
8% (8/101) developed protective levels of antibody (~IU/~l ~10). The
geometric mean titer for responders with antibody ~10 mIU/ml was 19.9 mIU/~l.
One hundred mentally retarded individuals have received three 20 mcg doses of
vaccine. At one month the seroconversion rate (S/..i :::,2.1) was 201 (20/100)
with 11% (11/100) developing protective levels of antibody (mIU/ml :::.10).
Responders with titers of at least 10 mIU/ml had a geOl'lletric 11ean titer of
38. 7 mIU/ml.
No serious or alann1ng adverse reactions attributable to vaccine have been
31731/1
1/11/86
STUDY 815
00829
PROGRAl'l: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,

Study 815
PURPOSE: To compare antibody and clinical responses to yeast

recombinant and plasma-derived hepatitis B vaccine
a110ng:
l Mentally retarded individuals who are negative for

hepatitis B virus serolog1c markers.
1. Yeast Recombinant Hepatitis 8 Vaccine

Lot 993/C-K937 (20 mcg/HBsAg/m1)
2. Plasma-Derived Hepatitis B vaccine
lot 2277K (20 mcg HBsAg/ml
PRIMARY Solko W. Schalm, M.D.

INVESTIGATOR: Department of Internal Medicine and Gastroenterology
University Hospital Dijkzigt
SECONDARY Or. Rudolf A. Heijtink

INVESTIGATORS: Oepartllent of Virology
Erasmus University
Or. Maria Alida van de Velde
Or. Mr. Willem vJn den Bergh - Stichting
STUDY LOCATION: Or. Mr. Willem van den Bergh-Stichting

University Hospital Oijkzigt
32341/l
l /21 /86
00830
Study 815

mentally retarded individuals. and 90 health care
personnel, who are negative for HBsAg. ant1-HBc,
anti-HBs, have a nonnal ALT and have not previously
STUDY PROCEDURE: Mentally retarded individuals and health care
personnel are · randomly assigned to receive either
yeast recombinant or plasma-derived hepatitis B
vaccine. stratified by sex and age.
Mentally retarded individuals and health care
personnel receive a 0.5 ml (10 mcg HBsAg) or a 1.0 ml
(20 mcg HBsAg) intramuscular injection of yeast
recombinant vaccine or a 1.0 ml (20 mcg HBsAg)
intramuscular injection of plasma-derived vaccine at
o. l, and 6 months.
A blood sample 1s obtained fro~ each study participant
approximately three weeks before the first injection
of vaccine. Post-vaccination blood samples are
obtained from mentally retarded indivtduals at 3, 7,
and 12 months and from health care personnel at l, 2,
3, 6, 7. 9 and 12 months. Blood samples are obtained
at 24 months from those participants who have
seroconverted.
anti-HBs and ALT. Samples may be assayed for yeast
> 25 mlU/ml may be tested for anti-a and anti-d
subtype specificity. - -
RESULTS: Clinical follow-up data and serologic results are not

32341/2
l /21 /86
Study 889
00831
PROGRAfil: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,

Study 889

1. Mentally retarded individuals who are negative
VACCINE: Yeast Recomb1nant Hepatitis 8 Vaccine

Lot 993/C-K937 (20 mcg/HBsAg/ml)
PRIMARY Robert P. Perr111o, M.D.

INVESTIGATOR: Director, Gastroenterology
SECONDARY Oliver H. Lowry, M.D.

INVESTIGATOR: Department of Pharmacology
Washington Univ. School of Medicine
STUDY LOCATION: Beverly Farms Foundation

Godfrey, Illinois 62035
~t. Louis, Missouri 63125
DATE STUDY INITIATED: June 19, 1985
STUDY POPULATION: The study population consists of approxi111ately 250

mentally retarded individuals, above 5 years of age,
and 50 health care personnel, who are negative for
HBsAg, anti-HBc, ant1-HBs, have a normal ALT and have
23941/4
1/3/86
00832
Study 889
STUDY PROCEDURE: Mentally retarded individuals are randomly assigned to

one of two groups, stratified by sex and age. Health
care personnel constitute a third group.
Mentally retarded individuals receive a 0.5 ml (10 mcg
HBsAg) or a 1.0 ml (20 mcg HBsAg) intramuscular
injection of vaccine at 0, l, and 6 months. Health
care personnel receive a 0.5 ml (10 mcg HBsAg)
intramuscular injection of vaccine according to the
same regimen.
. days after each injection of vaccine.
vaccine. Post-vaccination blood samples are obta1ned
at 1, 3, 6. 10 and 24 months.
All serum samples are assayed for HBsAg, anti-HBc and
anti-HBs. The pre-vaccination and 3 month post-
vaccination samples are also tested for ALT. Samples
may be assayed for yeast antibody. In addition,
samples with an anti-HBs titer ~ 25 mIU/ml may be
tested for anti-! and ant1-g_ subtype spec1f1c1ty.
RESULTS: MENTALLY RETARDED INDIVIDUALS

10 mcg Lot 993/C-K937 at 0, 1. and 6 months
20 mcg Lot 993/C-K937 at o. l, and 6 months
In.i ect 1on No.

Dose Cmcg) _!_ _2_ _ L
10 101 101 100
20 101 100 100
23941/5
1/3/86
00833
Study 889
RESULTS: (Contd) 2. Serologic Results:

Sero logic data at l month are ava t lab le for 101
mentally retarded 1nd1vtduals who received a 10
mcg dose and 100 mentally retarded individuals
who received a 20 racg dose of vaccine.
At 1 month, anti-HBs responses at10ng mentally
retarded individuals are as follows:
Gm (ldllhil)
Dose t AnH-HBs Positive A11 Aesponde~
(IIICg) S/N ::,2.1 lftIU/Ml ::,10 Vaccil'INS SIN ::,2.1 IIIIIU/al ~10
10 19 (19/101) 8 (8/101) o.s 8.7 19.9

20 20 (20/100) 11 (11/100) 0.6 13.7 38.7
Clinical follow-up data are available for 101 (10

mcg dose) and 101 (20 mcg dose) mentally retarded
1ndividua 1s fol 1ow1 ng the first injection of
vaccine and 101 (10 mcg dose) and 100 (20 mcg
dose) individuals following the second injection.
Clinical complaints and maximt111 teq,eratures
reported following each injection are provided in
Tables 1-4. In sunnary:
Clinical Dose % Freguencit b~ InJection No.

coml!la1nt i!!!9ll. 1 2 _3_
Injection Site 10 0 (0/101) 0 (0/101) NA

20 0 (0/101) 0 (0/100) NA
Systemic 10 2 (2/101) 0 (0/101) NA
20 1 (1/101) 0 (0/100) NA
No serious or alanning adverse reactions

23941/6
1/3/86
Table 1
PATIENT COUNT CLINICAL COl1PLAIHTS
RECOt1BINANT HEPATIT~S B VACCINE
STUDT 0889
TREATMENT
lOT NUMBER CK9]7
DOSE 10 MCG
PATIENT CLASS RE TARDED
I TOTAL VACCINEES C 101 PATIEHTSJ - DOSE 1 I

1• ----------------------------------------------------------------------------I
DATS POST VACCIHATIOH I t1Ut18ER
CLINICAL
COfflllAIHTS
l----------------------------------------------------------------------------1
• 0 • 1 • 2 I 3 I 4 I 5 I
WITH
ltONPlAINTS
•••••••••••••••••••••••••••••••••••l••-••••••l ..••••••••••••••••••••••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
-----------------------------------•---------- l ---------- l ---------- l----------t---------- l ----------t----------l-----------
svsTEt11c • 0 I 1 I O I 1 f O I O I I Z
• (· 0.11:0 I C 1.01.1 I C 0.01.J I C 1.DY.J I ( O.DY.J I ( O.OY.J I I C t .o:o
WHOLE BOOY/GEHEl!Al I O 1 I t I o I O I O I I 1
o.ox, ( 1 .01., I ( O.DX ) I C o.ox, I C 0,01.I I I o.ox, I • ( 1.0XJ
• • • • I I
HEADACHE I O 1 I O I O I O I O I f 1
O,DY.J C 1 .DY.J I C O.DY.J I I 0.07.J I I o.o:o I f 0,07.I I I I 1 .0;0
I I I I I I
RESPI RATORT I I 1 I D I 1 I O • O • I 2
0. 01. J ( 1 • OX J I I O. DX J I I 1. DY. J f I O. DY. I I I O, 0)0 I I I 2 • 01. )
I I I I I I
RHIHI TIS I t l • D I l I O I D I I 2
• c o.or., • c 1.ox1 I c a.ox, I c 1.01., I « o.ox, I • a.ax, I I I t .ox,
-----------------------------------1
PERsONs WITH tOttP U INTS •
----------l----------l----------•----------I----------I----------I----------I-----------
o I 1 I o I 1 I o I o I I t
I I o.ox, I « 1.ox, I c a.ox , I c 1.ox, I , o.ox1 I , o.ax, I I I t. ox,
-----------------------------------•----------•----------1----------1
PERSONS WITH NO CottPLAINTS I 101 I 100 I 101 I ----------1----------1----------1----------1-----------
100 I 101 I 101 I I 99
I UDO . DX) I ( 99.0Xl I U DO.OX! I ( 99,DX ) I ClOD.OXl I I JOO.OX) I I I 98 .0X J
-----------------------------------1----------1
PER!IONS WITH NO DATA I O I ----------1----------1----------1----------1
O I o I o I O I ----------1----------1-----------
O I I 0
I C O.OXJ I I o.oz, I ( o.o;o I ( O.OY.l I ( ,.ox, I ( o.ox, I I I o.ox,
0
0
,.,,
OIi
J::
Table 1 (cont.)
PATI,NT COUHT CLIHICAl COffl'LAIHTS
RECOMBINANT HEPATIT~S B VACCINE
STUDT : 0889
TREAfflENT
LOT NUt18EII CK937
DOSE 10 tttG
PATIENT CLASS: RETARDED
I TOTAL VACCIHEES t 101 PATIENTS) - DOSE 2 I

1I ----------------------------------------------------------------------------I
DAYS POST VACCINATION I tlUl1BER
CLINICAL
COttPLAINTS
1----------------------------------------------------------------------------
I O I l I Z I J I ~ • S •
IICOHPLA
WITH
tHTS
••••••••••••••••••••••••••••••••••••••••••••••1•••••••••••••••••••••1••••••••••1••••••••••1•••••••••••••••••••••1•~••••••••
-----------------------------------
PERSONS WITH Cot1PUINTS
t----------l----------•----------1----------l----------
I O I O I O I O I O
t----------1----------1-----------
I O I I 0
• I 0.01.t I t 0.01.1 I I 0.01.1 I I 0.01. 1 I I 0.01.1 I I 0.01.1 I I I 0 .01. 1
---------------------------·
PERSONS WITH MO COt1PLAI NT9
-------l----------l----------1----------1----------1----------•----------I----------I-----------
I 101 I 101 • 101 I 101 I 101 I 100 I I 101
I t 100.01., I 1100 . 01., • 1100.01.1 I 1100.01.1 • t100.01.1 I 1100.01.1 • • 1100.01.1
-----------------------------------1
PERsOHS WITH HO DATA I----------•----------•----------I----------I----------I----------I----------I-----------
o I o I o I o I o I o I I o
I I 0.01.1 I I e .01.1 f ( D.01.) f I D.01.J f I e.01.1 I C o.o;o I I I 0.01.)
0
0
OD
l>f
l.ll
Table 2
PATIENT COUNT MAXll1UH TEHPERATURES
RECOtl81NANT HEPATITIS B VACCINE
STUDT I 0889
TRU THENT
LOT NUt18ER CK937
DOSE 10 t1CG
PATIENT CU SS: RETARDED
I TOTAL VACCIHEES ( 101 PATI ENTS I - DOSE 1 I

1---------------------------------------------------------------------------------------I
I DAYS P09T VACCINATION I NUMBER
NA)( TEHPERATURE
(DEG F. ORALI
l---------------------------------------------------------------------------------------1
IO I l It I l I ~ I 5 I I
MITH
lnAXTENP
••••••••••••••••••••••••l••••••••••••••••• ..•• l••••••••••••••••••••• I••••••••••
I
•••••••••• ••••••••••l••••••••••I••••••••••
< tt I ~ • M I ~ I 81 I M M I %
81 .2:0 I I u .2;0 I , 89. uo I c ei .9;0 I I es . oi, , e8.1Y.1 I I ss.1tz 1
I I I I I
99 - 99. 9 I 1s I 16 I 11 I 16 I 11 12 I 38
14.91.I I I 15.8Y.J I C 10.9Y.J I I 16.21.J I I 11 .01.I I ll.9Y.J I I 37.6Y.I
I I I I I
100 - 100 , 9 I 4 I 1 I o I 1 I 1 o • 6
4,0Y.J I C 1 ,0Y.I I I 0.0Y.I I C l .0Y.I I I 1. 07.I I 0.0Y.I I C 5.9Y.I
I I I I I
101 - 101 . 9 I o I o I o • 1 I o o I 1
I ( O.0Y.I I C 0.0Y.I I C 0.0Y.I I I 1 .0Y.J I I O.0Y.I I 0.0Y.I I I 1.ax1
------------------------l----------l----------l----------t----------1----------l----------1---------------------1-----------
TEMPERATIJRE TAKEN I 101 I 101 I 101 I 99 I 100 I 101 I I 101
I (100.0iO I n oo.0Y.I I n oo.0Y.I I C 98.0iO I I 99,01.1 I 1100.0Y.I I I 1100.0Y.)
------------------------1----------1----------1----------1----------1----------1----------t---------------------1-----------
TB1PERATUlE NOT TAKEN I o I o I o I 2 I 1 I o I I a
I I O.OY.I I I O.OY.J I I 0.0Y.J I I z.01.1 I I 1 .17.J I C 0.01.1 I I I 0.0Y.I
0
0
OD
""a-
Table 2 (cont . )
PATIENT COUNT NAXINU11 TEHPERATIJRES
RECOt!8INANT HEPATITIS B VACCINE
ST\JDY I 0889
TREATNENT
lOT NUt1BER CK937
DOSE r 10 rtCG
PATIENT ClASS: RE TARDED
I TOTAl VACCIHEES C 101 PATIENTSI • DOSE t I

1I ·--·--························-·--·-·····--··-·······················--·-·---·-········1
DAYS POST Vl CCINl TIOH I NUMBER
HAX TEttPf:Rl TIJRE
f DEG F, OR Al J
1I
-•••·•··················--•·······--·························•·•···············••······1
O I l I Z I 3 I " I 5 I I
MITH
• HlX TENP
.................................................................... ,................................ l••··--··••1••········
I I
< '99 88
l 88. 0,0
96
C 95.01.1
'
I
93
C 92. UO
85
•I C 84.Zll 'II 86 90
I C 90.0lO
I 8t..OY.I
I
I
I
"'
I f "8. 3ll
99 • 99. 9 10
10 ,0iO I
5
s.o;o 'c
I
I
I
6
s.,:o •
I
I 14 I n I 10
c n.,:o I , n.o:o I c 10.0,n
I I
I
I•
I
I
I 28
• ( 27. 7ll
I
I
1 00 • 100.9 l 0 I z I 1 I 1 I 0 I I 3
1 .01. 1 C 0.07.I . r Z ,0)0 I C 1.or.t I 1 1.01.1 I c o .o:o I I • 3.0:0
I I I I I I
101 • 101 . 9 1 0 I 0 I 0 I 0 0 I I 0
1. 0;0 C 0.01.t I r 0.01. t I •
t 0.01.1 I t D.DY.) I ( 0. 01. t I I t D.07.1
102 • 102. 9 I o I O I· o I 1 I o I D I • l
I c 0.01.1 I I o.o;o I 1 0.01., I 1 1.01.1 I I o.or.1 I c o.o,o I I f 1 .01.1
··-········-··········-·1I ··-·······1··-·······1
TEMPERATURE TAKEN 1 00 I 1 01 I
··-·······1··········1
101 I 101 I
·---·-··-·1
100 I
--··-···-·1·----·-···-··········1
1 00 I •
···········
1 01
I I 99.07.J I uoo.0,:1 I noo.o,: , I n oo.or.> I c 99.or.t I t 99 . 01.1 I I n oo.01.1
-··-·······-··-·-·-·-·-·1-·---··--·1·--···-·-·1
TENPERATURE NOT TAKEN I 1 I O •
····-··-··•·-·-·-···1
0 -I O I
-·-···-···
1
1I ·--·-·-·--1---··-··------·-·---·•·--·-······
1 I • o
I I 1 .01.1 I I o.o:o I ( 0.01.J I ( o . or., I ( l.0iO • ( 1 .01. , I • r o.o:o
0
0
or,
vf
~
Table 3
RECOtllINANT HEPATITIS B VACCINE
SMY 0889
TRUTl!EITT
LOT NUN8ER I CIC937
DOSE 20 tlCG
PATIENT CLA'9: IU:TAllDffl

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUl18ER
CLINICAL
C0t1PLAINTS
l----------------------------------------------------------------------------1·
I o I 1 I t I l I 4 I s I
WI TH
•cot1PLAIHTS
· •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• l••••••••••l•••••••o•l••••••••••l•••••••••• I••••••••••
-----------------------------------l----------l----------l----------1----------1----------1----------l----------l-----------
sysnHic I D I O I 1 • 0 I O I D I I 1
I I o.o;o I 1 0.01., • c 1.0:0 I 1 0.01., I c 0.01., • 1 o.o;o I • 1 1 .0;0
I
Nt!DLE BODY/GENERAL I o I O I 1 I o I O I O I I 1
0.0X) I ( 0 . 07.) I ( 1.07.) I I 0.07.1 I ( 0.0XI I ( o.ox, I • ( l .0XI
• I • I • I I
HEADACHE I 0 • 0 • 1 I O I O • 0 I I l
I I 0,0XJ • ( 0.07. J. I 1 .07.1 • I 0.07.1 • C D.07. I • I 0.07.) I • C l,0XI
-----------------------------------•----------•----------•----------1----------1----------•----------l----------•-----------
PERSONs Wint COttPLAIHTS • 0 • 0 • 1 I o I o I O I I 1
I I 0.07. 1 • I 0.07.) I C 1 , 07.J I I 0.07.1 I I 0.07. 1 I I 0.07. 1 I I I l .OiO
-----------------------------------•----------1----------1----------
PERSONS Mlllt HO COMPLAINTS I 101 • 101 I 100
•----------1----------1----------1----------1
I 101 I 101 I 101 I I
-----------
100
I uoo.o;o I (100.07.) I I 99.07.) I UDO.DY.) I UD0.DXJ I (100.DXJ I I I 99.0X I
-----------------------------------1
PERsOHs NITlf NO DATA I
----------
O I
I----------
O I
I----------
O I
I----------I----------I----------I----------
O I O I I I
I-----------
I 0
I I o.o;o I 1 0 .07.1 I I o.ox1 I I o.o;o I 1 0.01. 1 I I o.o;o I I I o.o,o
0
0
OI
t.,.I
0:
Table 3 (cont.)
REC0t1BINANT HEPATITI S B VACCINE
STUDY OBB9
TREAfflEHT
LOT HUtl8ER : CK'J37
DOSE I 20 t1C&
PATIENT ClASSI RETARDED
I TOTAL VACCINEES C 100 PATI EHTS J - DOSE! •

1----------------------------------------------------------------------------
• DAYS POST VACCINATION II NUMBER
CLINICAL
COMPLAINTS
•----------------------------------------------------------------------------1
I O I l I 2 I 3 • - I S •
WITH
.COMPLAINTS
••••••••••••••••••••••••••••••••••• I•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
----------------------------------- 1---------- 1---------- I ---------- I---------- I----------I----------I----------I-----------
PERSotr.l WITH Cot1PLAIHTS I O • 0 I O • 0 • 0 I O I I O
• C 0.0X) . I 0.OX) I I 0.0X I • C 0.0XI • I 0.0X) I C 0.0X I I I f 0.0X t
------- .--------------------------- •----------•----------
PERsOHs WITH NO COHPLAINTS • 100 I 100 l----------•----------•----------1----------1----------1-----------
I 100 I 100 I 100 I 100 I I 100
I Cl00.0X) I Cl00.0Xt I 1100.0X J I Cl 0D.0XI I ClO0.0X J I Cl00.0XI I I Cl00.0X J
-----------------------------------1---------- I ·---------l----------l---------- •----------1---------- 1----------1-----------
PERSOH, WITH HO DATA I o I o I o I o I o I o I I ·o
I C 0.0XJ . C 0.0XI I C 0,0Xl I I 0. 0XI I I 0.0XI I I D.0XI I I f 0.DXJ
0
0
,.,.
OIi
..0
Table 4
PATIENT COUNT MAXIMUr'I TEMPERATURES
STUDT 0889
TREATt1ENT
LOT HlltlBEI! CIC937
DOSE I 20 t1C6
I TOTAL VACCIN£ES ( 101 PATIEHTSt - DOSE 1 I

1I ---------------------------------------------------------------------------------------I
NAX TEHPER ATURE
lDE& F, ORALt 1
l---------------------------------------------------------------------------------------1
0 I 1 I ! I 3 • 4 • 5 I I
WITH
I ltAX Tl:HP
•••--•••••••••••••••••••l••••••••••l•••••••• .. l•••••••••••••..••••••••••••••••••••'"'••••••l••••••••••l••IHf•••••• I••••••••••
• I 1 • I 1 • I
< 99 I 88 I 93 I 89 I 83 1 es I 86 I I u
I ( 88.01.1 I ( 92.1)0 I ( 88 . 11. 1 I C 8 2.21.1 I I 8 4.ZY.I I ( 86.01.1 I I I 61 .4%1
I I I I I I I I
99 - 99. 9 I 11 I e 1 11 I 17 I 14 I u I I 33
I I 11. 0X I • I 7.9Y. I I ( 10.9'/. t I I 16.81.t I I 13.91. 1 I l u .01. 1 I I I 32. 7Xt
I I I I • I I I
100 - 100. 9 I 1 I o I 1 I 1 I z 1 1 I D 6
1I I ( CI.0Y.I I I 1.0XI I I 1.01.1 1 l 2.0Y.I 1 I 1 .01.1 I
1 .01. 1 I I 5 .91.I
------------------------l----------1
n:HPIERATURE TAKEN 1 100 I
----------l----------l----------1
101 I 101 I 101 •
----------1
101 I
---------1---------------------l-----------
100 I I 101
• 1 n.0,: 1 I uoo.or., I 1100.0;0 I u oo.01.1 I uoo.ox, I 1 99.01. 1 I I 1100.0;0
------------------------1----------1----------1
n nPERAT\Jl!E NOT TAKEN • l I I I
----------.
O
1I ----------1
I •
----------1
0 I
----------1---------------------1-----------
l I I O
1 I 1. , 1. 1 I C o. 0Y. t I I O. 07. t I C 0. 07. 1 • I 0. 07.1 I I 1. OY. I I I I o, OX I
0
0
0,
.c,
0
Table 4 (cont.)
PATIENT CCIU'fT HAXIt1Ut1 JEHP(RAl\lllES
RECot1BIHANT HEPATITIS 8 VACCINE
STUIJY I 0889
TREAfflEHT
LOT NUt18EII : Ck.937
DOSE 20 t1CG
• TOTAL VACCIHEES I 100 PATIENTS! - DOSE 2 I

•l---------------------------------------------------------------------------------------1
DAYS POST VlCCIHATION I Hlt18ER
NAX TE"PERATURE
IOEG F, OR ALI
•--------------------------------------------------------------------------------------1
• 0 I 1 • t I 3 • 4 • !J I I I NAXWITH
TEtlP
a••••••••••••••••••••••••••••••••••l•-••-•••••••n•••••l••••••••••l••••••••••••.. •••••••l•.. ••..•••l•••'"'•'"'••I••••••••••
• I I I I • I I
< 99 • 93 • ~ • e1 • e1 I H • 86 I I 67
I I n.o;:1 I 1 94.91.I I I e1.o;:t I I e1.,;o I 1 91.e:o I 1 87.8;o I I 1 67.oz>
• I I I I I I I
99 - 99. 9 I s I s • n I 11 I e • 10 I I 29
• f 5.07.t. f 5.11.1. f 13.07.I If 11.17.1 If 8.27.1. I 10,27.l I I I 29.07.I
• I • I I I I I
100 - 100.9 I 2 I o I e I 1 I o • 2 I I tt
• l 2,07.J • l o.or.1 • ( 0 .07. I I f 1.0iO I l ,.o:o I I 2.07.1 I I f 4. 0l!I
------------------------l----------l----------l----------l----------•----------I----------I---------------------I-----------
TE11PERATURE TAKEN • 1 00 • 99 • 100 • 99 I 97 • 98 I I 100
I (100.0lO I I 99.0r.l I 1100.0lO • ( 99,0Y.I I I 97.0Y.I I l 98.0r.J I I 1100.01.1
------------·NOT
TEHPERAT\IR[
-----------
TAKfH
•----------1----------•----------1----------1----------1----------1---------------------t-----------
• o • 1 • 0 I 1 I J • 2 I I O
I I O,0lO • I 1 .0;0 I l 0,OlO I C 1 .0Y.I • I 3.0lO • I 2,01.1 • I C 0.01.I
0
0
0,
-
&::
TH/U .ASSt.MI CS/
HEMOPHILIACS
OOA42
Hemophiliacs and Thalassemics
Two stud1es have been initiated to assess antibody and cl inica 1 responses to
recombinant hepatitis B vaccine in persons with hemophilia or thalassemia.
Study 7g9 - Nev York, Me'd York - Dr. C. Stevens

Thirty-one thalassemic children, less than 16 years of age, \:1ho are negative
for hepatitis B serologic markers, are rece1v1ng either 5 mcg doses or 2.5 mcg
doses of vaccine lot 972/C-K444 at· o. 1, and 6 months. The vaccine is
administered intramuscularly.
Fifteen children have received three 5 mcg injections. At 7 months,
seroconversion was 89% (8/9) (S/N ~2.1) w1th a GMT for all vaccinees of 88
S/~. When the cut-off was S/ ~10, the seroconversion rate was 781 (7/9).
Sixteen children have received two 2.5 mcg injections of vaccine and 12 of
these have received the third injection. The seroconversion rate at 7 months
was l0OS (5/5) whether the cut-ff was S/N ~2.1 or S/N ~10. The GMT for a l l
vaccinees at 7 months was 200.0 S/N.
Twenty of the children enrolled in the study had pre-vaccination elevated ALT
l evel s which is characteristic of the clinical disease process of
thalasse11ia. One recipient of 5 mcg doses who had a nomal pre-vaccination
ALT level developed an elevation of ALT which was approximately 2.5 times the
upper limit of norul one month after receiving the first injection of
vaccine. This elevation was transient and returned to normal within a 110nth.
Study 861 - Mi l waukee, Wisconsin - Dr. S. Gill

The study population consists of persons with hemophilia who ~re negative for
hepatitis 8 serologic 111arkers. Participants under 20 years of age are
receiving 5 l'lltg doses while those who are 20 years of age or older are
receiving 10 mcg doses of vaccine at 0, l, and 6 months from lot 979/C-K564.
The vaccine is administered subcutaneously in this population.
Twelve hemophiliacs <20 years of age have received two 5 mcg injections and 5
of these have received the third injection. At three months, seroconversion
by either cut-off (S/N ~2.1 or mlU/ ml ~10) was 100% (8/8). The geonietric mean
titer was 143.2 mIU/ ~1.
Three hemophiliacs ::,20 years of age have received two 10 mcg doses of vaccine
and one has received all three injections. Serologic data at 3 months are
available for two vaccine recipients. Both participants ser-oconverted (S/N
~2.1) at three months. Neither developed protective levels of anti-HBs
(inlU/ml ~10) at that tliR. The geometric mean titer was 6.7 mIU/1111. No
serious or alarming adverse experiences attributable to vaccine ( either dose
regimen) have been reported.
wva/31371
1/21/86
00843

vaccine among thalassemic children who are negative
VACCINE: Yeast Recomb1nant Hepatitis B Vaccine

Lot #972/C-K444 (10 mcg/ml)
PRIMARY Cladd Stevens, M.D.

INVESTIGATOR: Lindsley F. Kimball Research Institute
New York Blood Center
310 East 67th Street
New York, New York 10021
SECONDARY Patricia Giardina, H.D.

INVESTIGATOR: New York Hospital - Cornell Medical Center
Margaret W. Hilgartner, H.O.
New York Hospital - Cornell Medical Center
Patricia E. Taylor, Ph.D.
Lindsley F. Kimball Research Institute
STUDY LOCATION: Lindsley F. Kimball Research Institute

New York Hospital - Cornell Medical Center
DATE INITIATED: August 1984
DA TE COMPLETED: In progress.
2472[/00871
1 /1 S/86
Study 799
STUDY POPULATION: The study population conshts of 31 thalassemic

children . 16 years of age or less. 1::1ho are negative
for HBsAg. anti-HBc and anti-HBs. and have not
PROCEDURE: Study participants are allocated to one of two groups

and receive the vaccine at 0, 1 and 6 months. Group 1
receives 0.5 ml (5 mcg) doses and Group 2 0.25 111
(2.5 mcg) doses. All injections intramuscular. The
parent or guardian are aslced to record the child's
temperature for 5 days after each injection and note
any loca 1 or systemic complaints. Hedi ca lly
significant events and therapies relating to the
child's pre-existing thalassemia will be recorded.
Blood specimens are obtained prior to vaccination,
monthly for 3 months and at 6 7. 9, 12 and 24 months
0
post initial injection.

All samples are assayed for HBsAg. anti-HBs, anti-HBc
and ALT by Or. Steven's laboratory. Samples may also
be assayed for yeast antibody at MSDRL.
RESULTS: THALASSEMIC CHILDREN:

5 mcg Lot #972/C-K444 at 0, 1 and 6 months.
2.5 mcg Lot #972/C-K444 at 0, 1 and 6 months.
1. Number Vacc·i nated:
Dose Level Injection Number

_1_ __2_ _L
5 111cg 15 15 15
2.5 mcg 16 16 12
24721/2
l /15/86
00845
Study 799
RESULTS (COl\lT.).: 2. Serologic Results:

and 5 recipients of 5 and 2.5 mcg injections
respectively.
Seroconversion was 89% (8/9) when the cutoff was
S/N ~2.1 among those receiving 5 mcg doses, with
a GMT of 88.0 for all vaccinees. When the cutoff
was S/N ~10, seroconversion was 1q (7/9).
Among the recipi~nts of 2.5 mcg doses,
seroconversion was 100% (5/5) whether the cutoff
was S/N >2.1 or S/N >10. The GMT for all
vaccinees - was 200.0~ Table l shows
seroconversion rates and GMT's for up to 9 months
of follow-up.
3. Clinical Complaints~
and 3 participants following the first, second
and third injections of 5 mcg doses; and for 16,
16, and 2 participants following the first,
second and third injections of 2.5 mcg doses.
reported during the 5 days following each
injection are provided in Tables 2 through 5.
FNQUenC:it: in 1. bx Injection No.

T:,pe of Ctllpl•int Dose Level 1 2 3
Injection Site s mcg 14 (2/14) 21 (3/14) 33 (1/3)

2.S ,neg 19 (3/16) 19 (3/16) 0 (0/2)
SystMk S .:9 36 (S/14) 14 (2/14) 0 (0/3)

2.S mcg 6 (1/16) 13 (2/16) 0 (0/2)

ALT Elevations
Twenty of the 31 children enrolled in this study
had prevaccination ALT levels ranging from 1.5-9
24721/3
1/15/86
00846
Study 799
RESULTS (CONT.): times the upper 1 imi t of normal. Most of these

remained at an elevated level during the course
of follow-up. Thalassemla is characterized by
increased serum alanine aminotransferase,
reflecting hepatic damage secondary to
hemosiderosis.
One recipient of 5 11cg doses who had a norma 1

prevaccination ALT level developed an elevation
of ALT which was approximately 2.5 times the
upper 1imit of normal one month after receiving
the first injection. This elevation was
transient and returned to normal within a month.
Adverse Experiences:
Two of the children enrolled in this study experienced

episodes of vomiting accompanied by fever within a day
of receiving their first dose of recombinant vaccine.
One of the children was a two-year-old who received a
5 mcg dose. His temperature was l04•F the day
following the injection. The child was examined by
the investigator who diagnosed a possible viral
infectfon. The second child was a one-year-old who
received a 2.5 mcg dose. A fever of 100.2°F was
recorded on the day of injection. A diagnosis was
made of a probable concurrent respiratory infection.
24721/4
1/15/86
TABLE 1
Antibody Responses Jl4nong Tha1assemic Children Fo11owing Vaccination with

5 or 2.5 mcg Doses of Yeast Recmt>inant Hepat'itis B Vaccine
lot I 972/C-k444 at 0, 1, and 6 Months in Study • 199.
- .. -·-. ·-
1, with Anti-His GftJ (S/Nl i Arti-HBs in rs/NJ
Till!! All Reu.vvlllrs . A11 Rea l'.IMl>rS
(bths) S/N ::, 2.1 SIM ::, 10 Vaccinees S/N ::,2.1 S/N ::, 10 S/N::,2. 1 5/~::, 10 Vaccinees 5/N::. 2.1 Sin::, 10
1 2S (4/16) 6 (1/16) 1.5 4.1 11.5 33 (5115) 13 (2/15) 2.2 12. 4 42.8
2 93 (13/14) 11 (10/14) 21.6 21.8 45.2 78 (7/9) 61 (6/9) 13.2 29.4 45.7
3 93 (14/15) 73 (11/15) 24.2 29.2 46.4 83 (10/12) 67 (8/12) 16. 1 29. 1 48.1
6 75 (9/12) 58 (7/12) 13.6 35.S 64.6 82 (9/11) 64 (1/11) 13.8 25.2 46.5
7 89 (8/9) 78 (7/9) 88.0 144 . 0 248.1 100 (5/5) 100 (5/5) 200.0 200 .0 200.0
9 90 (9/10) 90 (9/10) 91.4 146.S 146.5 100 (5/5) 100 (5/5) 150. 1 150. 1 150. 1
24721-5/cfs
12/20/SS
0
0
Cl)
.c,
~
Table 2
PATIENT COUNT CLJNICAL COMPLAINTS
REC0tl81NAHT HEPATITIS B VACCINE
5TUOY 0799
TIIUTltEHT
LOT NI.J'19EI! CK444
DOSE 5 t1CG
PATIENT CUSS: THALASSENICS
I TOTAL YACCitlE£S I 15 PATIENTS I - DOSE l - I

1----------------------------------------------------------------------------I
• DAYS POST VACCINATION I NUNBER
CLI NI CAL
COIIPLAINT9 l----------------------------------------------------------------------------1
WITH
lcot1PUIHTS
•••••••••••••••••••••••-•••••••••• l••••••••••••••••••••• l•••••••••• l•••••••••• l••••••••••l••••••••••l•••••••••• I••••••••••
I I I I I I I I
REACTION , LOCAL UHJECT. SITE> • I1 2 I O I O I O • O I I 2
I c 1.1r.1 I , 1 4.3lO I c 0.0;,:1 I c o.o;o I c o.o;o I f o.o;o • I c 14 . liO
-----------------------------------1
sOREHESS I
----------
1
l----------
I 2
l----------l----------
I o I o
1I ----------l----------l----------l-----------
o I o I I 2
I C 7.11.) I C 14.37.) I C O.0X) I ( 0.0XI I l o.o;,:, I C 0.0?.I I I ( 14.3?.)
-----------------------------------1----------l----------l----------
s,stEttic I 1 I 2 I o I
l----------l----------
1 I 2
l----------l----------l-----------
I o I I s
I ( 7. 17.I IC llt . 37. 1 I C 0.07.I I I 7. 1%1 I I 15.4%1 I I 0.0?.I I I C 35.7iO
----------------------------------------------------------------------------------------------------------------------------
I
INTEGUtlEHTARY SYSTEM I 0 I 0 0 1 1 0 I I 2
o. o:o I 1 0.0;1.1 C o. 07. I ( 7.UO I 7. 7%1 ( o.ox, I c 14.3;0
I
RASH, HOS I D I D 0 1 l 0 I 2
0 . 07. I I I 0. 07.1 ( o.o:o C 7 .17. I ( 7.7iO I o.o;o I I 14.3?.I
I I
RESPIRATORY I 0 I l D 0 0 0 I 1
0.DlO I f 7.1:t.l C o.o;o ( 0. 0% I I o.o;o I 0.0%1 Ic 7 .lY.)
I I
PHARYNGITIS I SORE THROAT I I D I 1 0 0 0 0 I l
o.o;o I c 7.UO ( 0.0%1 ( •• 07.1 ( 0.0.iO I 0.O iO I c 7 . l Y.l
I I
NUSCULOSKELETAL I I
' (
0
o. ox I I c
0
0.0%) (
0
0. OY. I (
1
7.1)0 (
1
1.n1 I ,
0
0 . 0%1 I c
1
7 . li!I
ARH PA I N
DIGESTIVE SVSTEH
I
I
0
o.o;o •
•
•I
t
0
D.O?.l (
0
o.o;o (
1
7. l?. I (
l
7.7iO (
0
O. Oi!I
I
I
I
.
I
I
(
1
7 . 1%1
I l
7.lY.I II
l
7.ll'.I I
•
0. 1%1 (
1
7.ll'.I (
0
0. 07. I (
0
0.0:1.1 I•
I 3
I c 21.47.1
I I I
HAUSEA I l I 0 0 1 0 0 I I z
7.llO I I 0.0:t.l I 0.07.1 ( 7 .1%1 ( 0.07.) ( O.OXI I I I llt . 37. l
I I I
VOtlITING I 0 I l 0 0 0 0 I I l
( O.OXI I( 7 .17.) I O.OY.l ( 0 . 07. I ( O.Ol!I ( o. 07.l I I I 7 .1%1 0
0
'),
C
OIi
'IF
Table 2 (cont.)
PATIENT COUHT CLINICAL CortPLAINTS
RECO118INAHT HEPATITIS B VACCltlE
STUDY 0799
TREATHEHT
LOT NU1111ER CK444
DOSE 5 t1CG
PATIENT CUSS: THALASSEnICS
I TOTAL VACCINEES I 15 PATJENTSI - DOSE 1 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUH9ER
CLINICAL
COMPUIIITS
1-------------------------------•··-·-···--·-·-··-·--------------------------•
I t I l • 2 • l I 4 I S I
MITH
lcONPLAINTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••I••••••••••
~GANS OF SPEtlAl SENSE I• O
I
I O
•
• 0
•
I l
I
I l
•
I O
I
I I
I l
• I 8.0%1 f C I.OX> • C O.OX> I I 7.1%1 I I 7.T/.1 I C O.OZ> • I C 7.lY.>
I I I I I I I I
EARACHE • 0 • o I 0 1 l I l I O I I l
I c t.o;o • c o.o:o It a.ox,• t 1.1 ✓.1 I c 1.n1 I, o.o;o I • 1 1.1x1
-----------------------------------1----------1----------•----------l----------l----------•----------l----------•-----------
PERSOIIS WITH tOOPLAIHTS I 2 I 4 • O I l I 2 I o I I 7
I I 14.lX> I I 28.6XI • I O.OX) I I 7.1%1 I I 15.4XI I I O.OX> I I I 50.0Xl
-----------------------------------1----------•----------l----------l----------l----------l----------l----------•-----------
PERSotlS WITH HO COMPUINTS I 12 I 10 I 14 I lJ I 11 • 1 I I 7
I c es.1x, I 1 71.4XI I 1100.ox1 I t ,2.,x1 I I e4.6XI • 1100.or.1 I I c so.01.1
------------ ·----------------------1----------1----------l----------l----------•----------I----------I----------I-----------
PERSONS WITH HO DA TA I O I O I O I O I O f 0 I f 0
I I O.OX) I I 0.07.1 I I O.OX) I I O.OXl I I 0.07.1 I I O.OXl I I I O.OXI
0
0
OD
b
. ,0
Table 2 (cont.)
l!ECOl1BIHANT HEPATITIS B VACCINE
STUDT 07'19
TRUTMENT
LOT WIDER CK444
DOSE 5 11CG
PATIENT CLASS TIIAUSSEttlCS
----------------------------------------------------------------------------------------------------------------------------
1----------------------------------------------------------------------------r
I DAYS POST VACCINATION I IMfl!EI!
CLINICAL
Cot1PUIHTS
1--------------------------------------------------------•-------------------•
WITH
ICONPLUNTS
••••••••••••••••••••••••••••••••••• l••••••••••l•••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••I••••••••••
I • I I • • I I
REACTION, LOC~l UHJECT. SITE) I 2 I Z I 2 I l I 1 I O I I J
I I 14.37.J I I llt.lll I I llt.37.J I ( 7.lll I ( 7.77.J I l O.Oll I I I 21.4:'.I
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sORENess I Z I Z I 2 I 1 I 1 I O I I 3
I I llt.37.J I I 14.lll I l 14.lll I ( 7.17.1 I l 7.77.J t·, 0.07.1 I I I 21 . 47.1
I I I I I I I I
ECCH'Yt10S1S I O I 1 I O I O 1 0 I O I I 1
I I D.07.) I ( 7.17.J I f 0.07.) I f 0.07.J I ( O.OXI I t 0.07.1 I I I 7.17.J
-----------------------------------l----------l----------l----------l----------1----------l----------l----------l-----------
s~sTEt1IC I l I 1 I 2 I 2 I l I O I I 2
I I 1.1zt I 1 1.1%1 I 1 14.37.1 I , 14.lll I , 1.1x1 I, o.oz1 • . I t 14.37.J
WHOLE BODY/GENERAL D D l I 1 0 I 0 I I l
o. oz, I• , • I
o.oz1 I , 7.lll I t 1.1:0 I t o.ox1 I , o.ox I I I I 7.17.I
I I I I I I I
HEADACHE D I D l 1 I 0 I 0 I l
D. 07.1 I c o.o;o I• 1 7 .17.1 I I • 7.17.1 I I D. DY. I I ( D.OY.I • • I I 7. lr. l
I I I I I I
INTEGIJHEHTARY SYSTEtt 0 •
I 1 I 2 I 1 I 1 I 0 I I 2
o.o:o I I 1.1;0 I l 11o.1z1 I , 1.1z1 I , 7,77.J I 1 o.oz1 I I I 14.lr.l
I I I I I I
RASH, HOS 0 I 1 I z I l I 1 I 0 I I 2
0 . 07. I I ( 7.1:'.I I I 14.37.1 I I 7. Ii'. I I < 7.77.1 I I o.oi, I I c 14.37.1
DIGESTIVE SYSTElf I 1 I D I 1 I D I O I O I I l
7.17.1 • c O.D7.1 • l 7.liO I < o.or.1 I I o.07.l I C O.Or.t I I I 7.17.>
I I I I I I I
DIARRHEA I 1 I O • l I D I O I O I I 1
It 7.17.I I l O.OZ) I l 7.17.1 I l o.ox, I C 0.07.) IC O.OY.I I I I 7,lX)
-----------------------------------•----------l----------l----------•----------l----------1----------1----------1-----------
PERSOltS WITH COttPLAIHTS I J I 3 • l I t I 2 I O I I 4
I l U.41.1 I l 21.47.1 I l 21.4XI I I 14.JXI I C 1S.41/.J I I o.o:o I I I 28.67.1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------1-----------
PERSONS WITH HO COttPUIHTS I 11 I 11 I 11 I It I 11 I 1 I I 1D
I ( 76.67.) I C 78.61/.I I I 76.6i0 I C es. 7)() I ( 114.67.1 I 1100.07.1 I I I 71.41/.I
0
0
~
\It
... 0
Table 2 (cont.)
PATIEHT COUNT CLINICAL Cot1PLAINTS
RECOt18IHAHT HEPAlITtS B VACCINE
STUDY 0799
lAEATHtNT
LOT t1Ut1BER CK44ft
oose 5 HCG
PATIENT CLASS: THALASSENICS
I TOTAL VACCIHEES ( 15 PATIENTS> - DOSE 2 I

l----------------------------------------------------------------------------1
CLINICAL
COttPLAlHTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I 1 I 4 I S I
NITH
ICOHPLAJMTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l•••••••••••••••••••••l•••••••••••••••••••••I••••••••••
-----------------------------------1----------•----------I----------I----------I----------I----------I----------I-----------
PERSOtls MITH HO DATA I o I o I o I o I 1 I o I I o
I c 0.07.1 I I 0.07.1 I c 0.01.1 I c 0.01.1 I, 7.17.1 I , o.oz1 I I 1 0 . 07.1
0
0
CD
""
-
I.II
Table 2 (cont.)
RECOt1BINANT HEPATITIS B VACCIHE
STUDY 0799
TRUTl1£HT •
LOT tU18ER CK44lf
OOSE 5 t1CG
PATIENT CUSS: THALASSEltICS
I TOTAL VACCIHEES l 15 PATIENTSI - OOSE 3 I

l----------------------------------------------------------------------------1
CLJHJCAL
COMPLAINTS
l----------------------------------------------------------------------------1
I O I l I t I 3 I '* I S I
WITH
IC011PLAINTS
••••••••••••••••••••••••••••••..•••l••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l••••••••••l•a••••••••
I I I I I I I I
RUCTION, LOCAL I INJECT. SITEI I l I 1 I l I l I l I D I I l
I c 33.3%> I I 33.3%1 • I 33.3%1 I c 33.3%1 I c 33.3%1 I r 0.0:11 I • c 33.JXI
-----------------------------------l----------l----------l----------l----------1----------1----------1----------•-----------
sOREHEss I 1 I 1 I 1 I 1 I 1 I o I I 1
I C 33.3?.J I I 33.3%> I I ll.3?.I I I 33.l%J I ( 33.3%1 I I 0.0%1 I I c 33.3%1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOtlS WITH C0!1PLA1HTS I l I 1 I l I 1 • l I D I I l
I c 33,3%1 I c n.1:1., I c 33.3%1 I , 33.3%1 I I n.3%J I r 0.0:1.1 I I 1 31.3;0
-----------------------------------•----------l----------1----------1----------1----------I----------I----------I-----------
PERSOHS WITH HO C0'1PUIHTS I 2 I t I t I 2 I 2 I D I I 2
I ( 66 , 7l'. I I I 66 • 7% J • I 66 • 7?. I I I 66 • 7% I I C 66. T,O • l 0. 0% I • • C 66 • 7% I
-----------------------------------•----------•----------l----------•----------l----------•----------1----------1-----------
PERSotlS WITH HO DATA I o I O I O I O I o I O I I O
I c o.oz, I I 0.0%1 I c 1.0%1 I c 0.0;1,1 I r o.or.1 I r o.or.1 I • c o.ox,
0
·::>
OD
IJI
N
.,
Table 3
PATIENT COUNT HAXlt1Ut1 TEHPERATURES
REC0tl3IHAHT HEPATITIS B VACCINE
STUDY 0799
TRUTHENT
LOT tu18EI! CK44•
DOSE 5 l1CC
PATIENT CLASS THAUSSEHJCS
I TOTAL VACCJNEES I 15 PATIEHTS J - DOSE l I

l---------------------------------------------------------------------------------------1
I OATS POST VACCIHATIOH I NUt18ER
MAX TEHPERATlmE
I DEG f, . ORAL I
l---------------------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I S I I
MITH
I 11AX UMP
•••••••••••••••••••••o•l••••••••••l••••••••••I•••••••••• •••••••••• ••••••••••!••••••••••
I
••••••••••l•••••••••• II••••••••••
NORMAL I It 4 It 4 ft I O I ft
28.67.) I 28.61.) I 28.61.) I 28.6i0 I 30.81.J I I O.OlO I I 28.67.l
I I
< 99 I It 4 7 s 6 I l I 2
za.6%J 1 2a.61.J I so.01.1 1 1s.11., , ti6.21., I noo.o;o I , 1ti.11.1
I I
99 - 99. 9 I 4 4 l ft 2 I o I 4
28.67.) I 28.67. ) ( 7.17.) I 28.67.) ( 15 . 47.) I I 0 . 07.1 I I 28. 61.1
I I
100 - 100.9 I 2 1 Z l l I O I 3
14.31.I ( 7.17.J I 14.37.1 I 7.lXI I 7. 77.1 I C 0 . 07.1 I I U.4i0
I I
103 - 103 . 9 I o 1 o o D I O I 1
I ( O.OiO I 7.UO f O.OlO C 0 . 01.l I 0.01. J I C O.OXI I I 7.lXI
------------------------l----------l----------1----------l----------l----------1----------1---------------------I-----------
TEHPERAT\JRE TAKEH I llt I 14 I 14 I 14 I 13 I 1 I I 14
I ( 93. 31. J I C 93. 3X ) I C 93. 37. I I I 93. 37. I I I 86. no I I 6 . 7X J I I I 93. JX I
------------------------l----------l----------l----------l----------
TEMPERAT\JRE NOT TAKEH I l I l I 1 I 1 I
l----------
2 I
l----------1
14 I
---------------------1-----------
I 1
I C 6. 77. I I l 6. 7l0 I I 6. 77. I I C 6 . 77.1 I C 13. 37.1 I C 93. 3X I I I I 6 . 7X l
0
.,.
C>
. I.II
~
Table 3 (cont. )
PATIENT COlMT HAXI11U11 TEMPERATURES
sn.or 0799
TREATMENT
LOT ~ER CK44ft
DOSE 5 HCG
PATIENT CLASS THALASSE"ICS
I TOTAL VACCINEES t 15 PATIENTSI - DOSE 2 I

t---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATJON f NUMBER
HAX TEHPERAJUl1E
tDEGF,0RAll
1
Io
---------------------------------------------------------------------------------------I
I l I 2 I 3 I lt I 5 I I
WI TH
I H,.l<TEttP
••••••••••••••••••••••••l••••••••••l••••••••••I•••••••••• •••••••••• •••••••••• •••••••••• •••••••••• l••••••••••I••••••••••
I I I I
NORMAL I 6 I 6 I 6 6 6 0 f 6
I 1 46.2;0 I 1 42.9Xt I I so.o;o 1 42.9% t , 1t&.2;0 1 1.0:r.1 I 1 42.9% )
I I I I
< 99 I ft I :, I 5 s s 1 I 3
I I Jo.ex, I 1 21.4;0 t c tt1.1;0 1 3s.1;0 1 :se.s:r.1 1100.0:r.1 I 1 21.tt;o
I I I I
99 - 99. 9 I 3 I :, I 1 3 l o I 3
I I ZJ.li( ) I t 21.tt:o I I e.li(J I 21.fti(J I 7.7:r.) I 0.0)0 I I 2l.4i()
I I I I
100 - 100. 9 I o I 2 I o D l o I 2
I I O. Oi(J I C lli.3i() I I o.o;o I 0.01., I I 7. 7l0 I 0.01. I I I I 14 . 3:1.1
------------------------1I----------1----------t----------
TEttPERATURE TAIIEH 13 I 14 I 12 It----------l----------t----------l---------------------l-----------
1ft I 13 I 1 I I 1ft
I I 86.7i0 f I 93.31.1 I I eo.Oi'.I I t n.1;O I I 86.7)() I I 6.?l!) I I I 93.3i0
------------------------1----------1
TEttPERATURE NOT TAKtH f Z I
----------1----------
1 I 3
t----------1----------t----------t---------------------
I 1 I 2 I 14 I
t-----------
I 1
I I 13.3i0 I I 6.7ZI I I Z0.0i'.I I I 6.7lo I I 13.3:1.I I C9J . 3i0 I I I f>.7iO
C>
0
OD
I.II
b
fl'
Table 3 (cont. )
PATIENT CO\JHT HAXlt1U111Ef1PERATURlS
l!ECotl8IHANT HEPATITIS 8 VACCINE
STUDY 0799
TRUTt1ENT
LOT NUl18ER CK444
DOSE S tltG
PATIENT CLASS THAUSSEt'IICS
( TOTAL VACCINEES C lS PATIENTS) - DOSE 3 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUt1BER
"AX TEMPERATURE
(DEG F, ORALI
(---------------------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I 5 I I
MITH
I t1l)( TEMP
••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••••••••••••••••••••••••
I I I I I
l•••••••••••••••••••e•••••••••••
I I
I••••••••••
I
NORl1AL I 1 I l I 1 I l I 1 I O I I 1
• l 33.lX) I l 33.lX) • I 33,3ZI • I 33.3XI • I 33.lX) I C D.OZI . I ( 33.3Zl
I I I I I I I •
< 99 I 2 I 2 I 2 I t I t I o I I 2
1 c 66. 1x, I 1 66. n:,
I , 66 . n:,
I , 66 • 110 I 1 66 • n:,
1 c o. o;o I · I , 66 • n 1
------------------------1----------•----------1----------•----------1----------•----------1
TEMPERATURE TAKEN I 3 I 3 I 3 • 3 • l I O I
---------------------1-----------
I l
IC 20.0ZI • I ZO.OZ) IC ZO.OXI I I 20,0ZI • I 20.0XI I C O.OZl • I C 20 . DXI
------------------------l----------l----------l----------•----------l----------l----------1
TEMPtRATURE HOT TAKEN I 12 I 12 I 12 • 12 I 12 I 15 I
---------------------1-----------
I 12
I ( eo.oz, I C eo.oz , I C 80.01. ) I C 80.0ZI I I ea.ox, I 1100,0ZI I I I 80 . 0ZI
0
0
CD
1.11
I.II
...
Table 4
RECOt18IHAHT HEPATITIS B VACCIHE
ST\JOY 0799
TREATNENT
LOT tlUNBER I CK441t
DOSE 2.5 t1CG
PATIENT CL.US: THALASSENICS
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I 16 PATIEHTSI - DOSE l I
l----------------------------------------------------------------------------1
l----------------------------------------------------------------------------1
CLINICAL
COMPLAINTS
.............................•..... I
,
I
O
..•....... I
I
1
,
.......... I 2
,
...••.....
I
I 3
,
..........
I
I 4
..........
I
I
, I
5
.......... I
I
, WITH
,
.......... ICOHPLAIHTS
......... . ,
I
REACTION, LOCAL CINJECT. SITEI I 2 I l I O I O I O I O I I 3
I l 20.0XI I I 6.37.1 I I 0.07.1 I < O.OZI I < O.OXI I < O.OXI I I I 18.&XI
-----------------------------------l----------l----------1----------1----------1----------l----------l----------l---·-------
SOREHESS I 2 I 1 I o I o I o I o I I 3
I 1 20.ox1 I 1 6.3XI I < o.ox1 I < o.ox1 I < o.o:o I c o.o:o I Ic 1e.ex1
-----------------------------------1----------l----------1----------l----------l----------l----------l----------l-----------
svsnN1c I. 1 I O I O I O I O I O I I l
I < 10.0%1 I ( O.OZI I I O.OXI I I o.o:o I < O.OlO I l 0.07.1 I I I 6.3Zl
------------------------------------------------------------------------------------------------------~
I I I I I I I.
RESP1RAT001' I l I O I o I o I o I o I I l
I 1 10.ox, I I o.o;o I c 0.0:r.1 I I o.ox1 I < o.ox, I c o.o:o I I 1 6.37.1
I I I I I I I
IIHINITIS I 1 I o I o I o I o I o I I 1
IC 10.0;0 I l 0.0%) Il o.o:n I l 0.07.) Il O.OZ) I C 0.01.I I I l 6. 37.l
I I I I I I I
PHARYNGITIS (SORE THROAT> I 1 I O I O I O I IO 1I O I
I t 10.0Y.) I l O.OXl It O.OXI I I O.OXJ I l O.OXJ I
I I 6.3Z) l O.OXJ I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSDNS WITH CotlPlAitlTS I 3 I 1 I O I O I O I O I I 4
I < 30.0XI I < 6.]XI I l O.OZI I l O.OiO I I 0.0)() I I 0.07.) I I ( ts.OZ)
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH HO COHPLAIHTS I 7 I 15 I lf• I H, I 16 I 6 I I 12
I ( 70.0XI I I 93.&XI I 1100.0XI I 1100.07.1 I 1100.0Z) I 1100.0ZI I I I 75.0?.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH NO DATA I O I O I O I O f O I O I I 0
I I o.or.1 I ( O.OXI IC O.OZ) I l O.OXI I I O.OY.I I ( O.OXI I If O.OXJ
0
0
a,
\J'1
C1'
--
Table 4 (cont. )
STUDY 0799
TREATt1tNT
LOT NUt18ER Ct<444
DOSE 2.5 tlC&
PAlUHT CUSS lHALASSE"lCS
I TOTAL VACtlHEES l 16 PATIEHTSI - DOSE 2 •

1----------------------------------------------------------------------------I
CLINICAL
tONPLAlHTS
1----------------------------------------------------------------------------I
I O • 1 I 2 I 3 I ,. I 5 I
WITH
IC011PLAINTS
·-·································•········••1••·················••1••······••1••······•·1••······••1••······••1••········
I I I I I I I I
REACTION, LOCAL UHJECT. SITU I 3 I O I O I O I O I a I I 3
I l 23.lXI I ( a.ox, I ( a.oz, I I O.OZI I ( O.OZI I ( a.ox, I If 18.8ZI
-----------------------------------1----------l----------l----------l---·------l----------l----------1----------l-----------
sOREHESS I 1 I a I a I o I o I o I I 3
I c 21.1x1 I c o.oz1 I I o.oz, I c o.oz, I i a.oz, I c a.ox, I If 1e.sx1
-----------------------------------l----------l----------l----------l----------l----------l----------l----------1-----------
svsnn1c I 2 I l I l I O I O I 0 I I 2
I ( 15. lt7. I I ( 6. 71.1 I I 6, 31.1 I ( a . OX I I I O. 01. I I I o. oz I I I c 12. 5Z l
I
ORGANS OF SPECIAL SENSE I 1 I O I O I O I O I o I • 1
I c 0.01.1 I c a.ox, I c o.o:o I c o.ox1 I c o.ox1 I
1. 1z1 I f 6.37.1
I I I I I
OTHER I 1 I O I O I 0 I 0 I 0 • • l
7.77.1 I I 0.0XI I I 0.0)0 If o.o:o I I o.o:o I I 0.07.I I I I 6.JZ)
I I I I I I I
PSYCHIATRIC/BEHAVIORAL I l I 1 I I I O I O I O I I l
1 7. 77.1 I 1 6.77.1 I c 6.JXI I c o.oz, I I o.o;o I f 0.011 I I c 6.37.1
I I I I I I I
IRRITABILITY I 1 I 1 I l I O I a I a I I 1
I I 7. 7X I I C 6. 7Z I I I 6. Ji( I I C O. Or. I I C 0. ox I I ( 0. Or. I I I I 6. 3X I
-----------------------------------1----------1----------I----------I----------I----------I----------I----------I-----------
PERSot~ WITH tOHPLAINTS I ,. I 1 I 1 I o I a I o I I ,.
I C 30.e:o I I 6.7X) • I 6.3i() I f 0.07.) I I 0.0Y.) I I a.o:o • • I 25.07.1
--------·····-·-··--------·-------·1·---------l----------l----------l----------l----------l----------1----------1-----------
PERSOOS WITH HO COffllLAIHTS I 9 I 14 I 15 I 16 I 15 I 3 I I 12
I I 69.2)0 I C 93.3XI I I 93.8)0 I uoo.o:o I 1100.07.1 I Cl00.0r.l I I ( 75,0r.l
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l----·------
PEIISONs MITH NO DATA I o I o I o I o I 1 I o I I o
I c 0.07.1 I I a.ox, I c o.o;o I c o.or.1 I c 6.37.1 I I o.o:o I I c a.ox,
0
0
.:,,
.. I.II
-..I
Table 4 (cont. )
PATIENT COUNT CLINICAL Cot1PLAIHTS
RECotfflIHAHT HEPATITIS B VACCINE
STUl>'I' 07'19
TREATHEHT
LOT I-M1BER CIC444
DOSE 2.s ncG
PATIENT CUSS TIIA lASSEHICS
• TOTAL VACCitlEES ( U PATIENTS I - DOSE l •

•---------------------
•
·------------------------------------------------------1
DA'l'S POST VACCIHATIOH I NUtt8Elt
CLINICAL •---------------------------------------------------------~------------------• WITH
COHPLAIHTS I o I 1 I z I 1 • 4 I s I •cOffl'LAINTS
···································•········••l••········•········••l••······••l••·················••l••··············••D••
-----------------------------------l----------l----------l----------l----------l----------l----------1----------1-----------
P£RSOHs WITH COttPUJNTS • 0 I O I O I O I O I O • • O
I I a.ox, I C o.o,o I C 0.01.1 I C o.o:o I C 0.07.) I I 0.07.1 I I f o.o;o
-----------------------------------1----------l----------t----------l----------l----------l----------1----------I-----------
PERsOHs Wint HO COMPLAINTS I 1 I Z • 2 I Z I Z • 1 I • 2
I 1100.01.1 I 1100.01.1 I 1100.07.1 I 1100.01.1 I 1100.01.1 I 1100.07.1 I I 1100.07.1
-----------------------------------1----------l----------l----------l----------l----------l----------1----------I-----------
PERsotts wnH HO DATA I o I a I o I o I o • o • • o
I I 0.0%1 I C 0.0%1 I ( 0.01.1 I ( 0.01.) I ( 0.07.1 I I 0.07.1 I I I O.OXI
0
0
0,
I.II
0,
.,,
Table 5
PATIENT COUt-lT HAXIt1Ut1 TEMPERATURES
RECot18INAHT HEPATITIS 8 VACCINE
!ITUOY 0799
TREATNEHT
LOT NI.Jt1BER CK444
DOSE 2.5 ttCG
PATIENT CUSSI Tl1AUSSEl1ICS
I TOTAL VACCINEE!I I 16 PATIEHTSI - DOSE 1 I

1---------------------------------------------------------------------------------------I
HAX TEMPERATURE
IOEG F, ORll I
l---------------------------------------------------------------------------------------1
I O I l I 2 I 3 I 4 I 5 I I
WITH
I HAX TEMP
••••••••••••••••••••••••l••••••••••l••••••••••I••••••••••
I
•••••••••• ••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I
tlORMAl I 1 1 I 1 1 1 0 I I l
10.0:0 1 6.3:-:1 I c 6.3XI , 6.31.1 1 6.37.1 1 I
0.07.J I 1 6.J;n
I I I
< 99 I 4 10 I 8 10 11 5 I I e
40.01.1 I 62.s:o I ( SO.OZ) I 62.SXI I 68.&XI I 83.JiO I I I 50.0)()
I
99 - 99. 9 I 4 4 I 6 4 4 1 I I 6
40.01.1 t 25.0ZI I I 37,5?.I I 25.07.J I 25.0ZI I 16.T/.1 I I l 37.S7.I
I I I
100 - 100.9 I l o .I 1 o o o I I o
10.07.1 I I I
0.07.) 6.3?.l I 0.01.) I 0.0;:1 I 0.07.) I I I 0.0;:1
I I I
101 - 101. 9 I o 1 I o 1 o o I I 1
I c 0.01., I 1 6.37.J I I o.o;o c 6.11.1 1 o.o;n I o.o::o I I 1 6.3::o
------------------------l----------l----------l----------t----------l----------l----------1---------------------1-----------
TENPERATURE TAKEN I 10 I 16 I 16 I 16 I 16 I 6 I I 16
I C ,2.s;:1 I Cl00.01.1 I ClOO.O?.) I c100.o;:1 I (100.0XI I C 37.Sll I I ,100.0;:1
------------------------l----------l----------l----------l----------l----------t----------1---------------------1-----------
lENPERATURE HOT TAKEN I 6 I O I O I O I o I 10 I I 0
I C 37.SXI I C O.OY.I I I O.OY.I I I O.OY.l I I O.OY.I I I 6Z.5Y.l I I I O.DXI
0
0
0,
I.II
-0
·=
Table 5 (cont. )
RECot1BIHAHT HEPATITIS B VACCINE
STUDY 0799
TREATMENT
LOT tu1BER CIC.444
DOSE 2.5 HCG
PATIENT CLASS THAUSSEHtC5

1---------------------------------------------------------------------------------------I
HAX TEHPERATURE
CDEG F, ORAL I
l---------------------------------------------------------------------------------------1
I O • 1 I Z I 3 I 4 I 5 I f
WITH
I NA>C lEHP
······················••1••······••1••········•········••1••········
I I I .................... I,.......... ,.......... I,..........
NORrtAl I 6 I 6 I 6 I 6 6 0 I I 6
46.27.) I I 40.07.1 ., C 37.SY.I I I 37.SY.l C 40.o:o I o,o;o I I I 37.s:o
I I I I I
< 99 I 4 I 6 I 6 I 6 6 3 I I s
30.81. J I ( 40.0XJ I ( 37 .SY.I I I 37 .s;o C 40.07.1 1100.0;0 I · I I 31. 37.1
I I I I I
99 - 99. 9 I 3 I 2 I 3 I 3 2 o I I 2
23.17.1 I C 13.37.1 I C Ul.81.1 I I 18.87.J C 13.37.1 I 0.0Y.I I I I lt,s;o
I I I I I
100 - 100.9 I ·o I 1 I 1 I 1 1 o I I :s
1c 0.01.1 I, 6.r1.1 11 6.:s;o I 1 6.3:o I• 6.r1.1 1 o.o:o I I 1 1a.ex1
------------------------l----------l----------1----------1----------1----------I----------I---------------------I-----------
TEHPERlTURE TAICEN I 13 I 15 I 16 I 16 I 15 I 3 I I 16
I I ai.JY.l I « 91,a:o I uoo.o:o I uoo.o:o I « 93.eio_ I , ia.e;o I I n.oo.o:o
------------------------l----------l----------1----------l----------l----------1----------1---------------------I-----------
TEMPERATURE NOT TAKEN I 3 I 1 I O I O I 1 I 13 I I O
1 c 1a.a1.1 I ( 6.1:0 I ( o.o;o I t o.o:o I 1 6.3:o I 1 &1.1Y.1 I I c o.o;o
0
0
OD
0-
0
-
Table 5 (cont . )
PATIEHT COUNT NAXIt1Ul1 TEl1PERATURES
REC0t18IHANT HEPATITIS 8 VACCINE
!ITIJOY 0799
TRUTNEHT
LOT NUteER CK'o44
DOSE Z. 5 t1C&
PATIENT CLASS THAUS!IEHJCS
I TOTAL VACCINEES ( 12 PATIENTS) - OOSE 3 I

1I---------------------------------------------------------------------------------------•
OAYS POST VACCINATION • .ut19ER
NAX TEMPERATURE
(DEG F, Off ALI
1I
---------------------------------------------------------------------------------------•
O I 1 I Z I 3 I 4 I 5 I •
WITH
• HAX TENP
Q•••••••••••••••••••••••l•••••••••••••••••••••••••••••••• •••••••••••l•••••••••• ••••••••••••••••••••••I•••••••••••••••••••••
• I I I I I I I
< 99 I 1 I o I l I o I 2 I 1 I • o
I (100.01.> • I 0 . 01., • I 50.01.l I I 0.01.1 I 1100.01. 1 I 1100.01.1 • • l 0.01.1
I I I I I I I •
99 - 99 . 9 I a I z I 1 • z I o I o I • z
I I 0.01.> I 1100.01.1 • , so . 01.1 • (100.01.1 I 1 0 .01.1 I 1 0.01.1 I I 1100.01.1
------------------------1----------1----------l----------l----------l----------l----------•---------------------
TEMPERATURE TAKEN I l I Z I 2 I 2 I 2 I l •
I-----------
I 2
If 8.37.> I I 16 . 71.l • 1 16.77. 1 I l 16.71.1 I I 16.7XI • 1 a.11.1 I I t 16.77. 1
------------------------ l----------
TEMP~ ATURE HOT TAKEH I 11
•----------l----------•----------
I 10 I 10 I 10
l----------•----------1---------------------1
• 10 I 11 I I
-----------
10
. I I 91 .71.) • ( 83.31.) • I 83.31.) • I 83.31.) • ( 83.3?.I • I 91.7?.) I • I 83.37. )
0
0
-
011
c,,.
....
Study 861
'\
00862
PROGRAP/l: Alum-Adsorbed Yeast Recombinant Hepatitis B vaccine,

Study 861.
PURPOSE: To assess antibody and c linica 1 responses to vaccine

in persons with hemophilia or homozygous siclcle cell
disease . who are negative for hepatitis B serologic
markers.

Lot #979/C-KS64 (10 mcg HBsAg/ml)
PRINCIPAL Joan Gill; M.D., Medical Director

INVESTIGATOR; Great Lakes Hemophilia Foundation
1701 w. Wisconsin Avenue
Milwaukee, WI 53233
SECONDARY Robert R. Montgomery, M.D.

INVESTIGATORS: Great Lakes Hemoph11ia Foundation
1701 W. Wisconsin Avenue
Milwaukee, WI 53233
Kathleen M. Marquardt. R.N.

Great Lakes Hemophilia Foundation
1701 w. Wisconsin Avenue
Milwaukee, WI 53233
Denise Lockhart. R.N.

Nurse Coordinator, Sickle Cell Clinic
Milwaukee Children's Hospital
1701 W. Wisconsin Avenue
Milwaukee, WI 53233
STUDY LOCATION: Great Lakes Hemophilia Foundation

Milwaukee Children's Hospital
1701 West Wisconsin Avenue
Milwaukee, WI 53233
24431/1
12/27/85
00863
Study 861
STUDY POPULATION: The study population will consist of 25-30

he1110philiacs of any age and either sex (pregnant women
excluded), who are negative for HBsAg. anti-HBc and
anti-HBs, have a normal ALT level and have not
previously received any hepat1tts B vaccine.
Under an addendum to the study, an additional
population of approximately 10 persons ( < 20 years of
age) with homozygous sickle cell disease, who are
undergoing chronic blood transfusion, and are negative
for hepatitis B serologic markers, will also be
included in the study.
PROCEDURE: Each participant receives an injection of vaccine at

0, 1, and 6 months. The vaccine is administered
subcutaneously to the hemophiliacs and intramuscularly
to the subjects with homozygous sickle cell disease.
Persons under 20 years of age are given a 0.5 ml (5
mcg HBsAg) injection of vaccine. while, those 20 years
of age and older receive a 1.0 ml ( 10 mcg HBsAg)
injection of vaccine. Vaccine recipients (or their
parents/guardians in the case of minors) will be asked
to record their temperature for 5 days after each
injection and to note any local or systemic complaints.
Blood specimens wi 11 be obtained prior to vaccination
and 1, 3, 6, and 8 months post-initial injection.
Sa!llples will be assayed for HBsAg, ant1-HBc, anti-HBs
and ALT at MSDRL. Samples with an ant1-H8s titer >25
mIU/ml w111 be further tested to determine the
relative proportions of anti-! and ant1-g_ activity.
Samples may be assayed for yeast antibody.
RESULTS: HEMOPHILIACS:
5 mcg (<20 years of age)

Lot #979/C-K564 at 0, 1, and 6 Months
10 mcg (~20 years of age)
Lot ~79/C-K564 at 0, 1, and 6 Months
24431/2
12/27/85
00864
Study 861
RESULTS: (Cont.) 1. Number vaccinated:
Dose Injection No.

Level _ ,_ _L _3_
5 mcg 9 9 0
10 mcg 2 2 0
Serologic data are available for 8 participants at
3 months who received 5 mcg injections and 2
participants who received 10 mcg injections. 7/8
month data are available for one participant from
each dose level.
At three months. all eight participants (100%) who
received 5 mcg injections seroconverted (S/N ~
2.1) and developed protective levels of anti-HBs
(mIU/ml ~ 10). The GMT for those responders was
143.2 mIU/ml.
Both participants who received 10 mcg 1nject1ons

seroconverted for anti-HBs (S/N ~2.1) at three
months. Neither developed protective levels of
anti-HBs (rAIU/ml ~ 10) at that time. The GMT for
those participants was 6.7 mIU/ml.
Refer to Tab le 1 for ant1-HBs responses and Gl4Ts
for other ti~e intervals.
3. Clinical complaints:
Clinical follow-up data for participants who
received 5 mcg injections are available for 10, 8,
and 5 vacc1nees after injection 1,, 2, and 3,
respectively. Among vaccinees who received 10 mcg
injections, clinical follow-up data are available
for 3, 2, and 1 participants after injection 1, . 2
and 3, respectively.
24431/3
12/27/85
00865
Study 861
RESULTS (CONT.): The overa 11 frequencies of complaints are

presented below.
Type of Dose Freauencv in I bv Iniection No.

Complaint Level 1 2 3
Injection 5 mcg 9 (1 /11) 13 (1 /8) 0 (0/5)

S1te 10 mcg 33 ( l /3) 50 (1 /2) 0 ( 0/1)
Systemic 5 mcg 9 (1/11) 13 (1 /8) 0 (0/5)

10 mcg 33 ( 1/3) 0 (0/2) 100 (l/1)
Refer to Tables 2 and 3 for listings of specific

c 11 n1ca l comp 1a1nts by 1nject1on number. Maximum
temperature data are provided 1n Tables 4 and 5.
HBV Markers (anti-HBC)
. b)(6)
One subject with hemophilia (case became
seropositive for ant1-HBc 2 months after the th1rd
injection of yeast recombinant hepatitis B vaccine.
At the time the subject was also seropos1t1ve for
anti-HBs with reported titers of 42769.8 S/N and
118121.4 mIU/ml. The vacc1nee was well; serum samples
were negative for HBsAg and ALT levels were normal.
Attempts will be made to obtain additional serum
samples.
Reactions Reported to the OOBRR
One patient (case rb)(G\ was hospitalized for a bleeding
telan~1ectasic site 1n the distal atrum of the stomach
(b) (6) after administration of the third injection of
vacc1ne. This 42 year old male with hemophilia had a
medical history significant for recurrent GI bleeding,
duodenal and antral gastric ulcer, and hemarthroses.
The patient was adminstered whole blood and
cryoprecipitate and was discharged after 5 days in
stable condition. The investigator stated the
patient's experience was not related to vaccination
with yeast recombinant hepatitis B vaccine.
24431/4
12/27/85
00866
Study 861
RESULTS (CONT.): PATIENTS WITH SICKLE CELL ANE~IA

1. Humber vaccinated:
Injection No.
_ l_ __2_ __3_
4 4 0
Serologic results are not yet available.
attributed to vaccination. Detailed data on
clinical complaints and temperatures following
vaccination are not yet available.
24431/5
12/27/85
Table 1
Antibody Responses ~ g Hemophiliacs Following Vaccination with

S n:g (Hamphi liacs < 20 years) or 10 mc:g (Henq>hll iacs ~ 20 years) Injections of
Yeast Recod>inant Hepatitis B Vaccine lot I 979/C-k564 at 0, 1, and 6 Months in Study "861
Sg lltenA>hl 1iacs < ~ Years of ~l 10 n:g lHemar>h i liacs > 20 Years of ~2

I with Anti-flls 6"T lmIU/111 ! 1,with Antl--HBs GPIT lmIU/11112
Time All Resoonders Al l Resoonders
(Nonths) S/N ~ 2. 1 raIU/111 ~ 10 Vaccinees SIN ~ 2.1 111IUl•l ~ 10 S/N~2.1 mlU/111 ~ 10 vacc\nees SIN ~ 2.1 11lU/11l ~ 10
---
19 (2111) 18 (2/11) 0.9 15.9 15.9 0 (0/3) 0 (0/3} 0.3
3 100 (8/8) 100 (8/8) 143.2 143.2 143.2 100 (2/2) 0 (0/2) 6. 1 6.1
6 100 (2/2) 100 (2/2) 223.J 223.7 223.7 0 (0/1) 0 (0/1) 1. 3
7/8 100 {1/1) 100 ( 1/1) 3878.3 3818. 3 3818.3 0 (0/1) 0 (0/1} 1.6
24431-1
0
12/27185 0
CJ>
..,
0-
Table 2
STIJOY 08E>l
TREATMENT
LOT tM18ER CK564
OOSE 5 11CG
PATIENT CLASS HEHOPHILIAC9
----------------------------------------------------------------------------------------------------------------------------
·
1----------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I HU1BER
CLINI CAL
CONPLAINTS
1----------------------------------------------------------------------------I
I o I l I 2 I 3 I 4 I 5 I
WITH
I COMPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••-••••••l••••••••••l••••••-••I••••••••••
I I I I I I I I
REACTIOtl, LOCAL UNJ[CT. SITE) I 1 I 1 I l I O I O I O I I I
I I '1.S:O I I 9.liO I I '1.1)0 I I o.o;o I I 0.0%) I I 0.0%) I I I 9.1)0
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sORENESs I 1 I 1 I 1 I o I o I o I I 1
I 1 9. 1x1 I 1 9.1x1 I 1 <i.1;0 I I o.o;o I I o.ox, I I o.o;o I I 1 9.1x1
I I I I I I I 1
SWELLING I l I o I 1 I o I o I o I I l
I I 9.lX) I I O.OXI I I 9.1:1.) I I O.OXI I I o.o;o I I 0.0)0 I I I 9.1%)
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
SYSTEHIC I 1 I 1 I l I 1 I 1 1 1 I I 1
I I 9.IXI I I 9.IXI I I 9.lXI I I 9 . 11.1 I I 9.lXI I I 9 .11.1 I I I 9.11.1
----------------------------------------------------------------------------------------------------------------------------
1 I I I I I I I
WIIOLE BODY/GENERAL I l I l I l I l I l I 1 I I l
I I 9 . lXI I I 9.11.1 I I 9.lX) I I 9 . lXI I I 9.lXI I I 9.lXI I I I 9.11.1
I I I I I 1 I I
SWE ATING I l I O I o I o I O I O I I l
I I 9.lXI I I O, OXI I I O.OXI I I O.OY.I I I D.OXI I I O.OY.I I I I 9,1%1
I I I I I I I I
FATIGIJE /WEAKNESS I 1 I 1 I l I l I l I l I I 1
( C 9 . lXI I t 9 . 1%1 I I 9.lXI I I 9. l XI I I 9 . 1%) I I 9.lXI I I I 9 . 1%1
-----------------------------------1----------l----------t----------l----------l----------1----------l----------1-----------
PERSOIIS MITH COIIPLAINTS I 2 I 2 I 2 I 1 I 1 I 1 I I 2
I C 18.2%) I I 18 . 2%1 I I 18.2XI I( 9. l XI I I 9.lXI I I 9 . lXI I I I 18 . 2%1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------1-----------
PERSOHS WITH NO CONPUINTS I 9 I 9 I 9 I 10 I 10 I 10 I I 9
I C 81.8%1 I C 81.8%) I I 81 . 8XI I I 90.9:t.l I I 90.'l:t.) I I 90.9)() I I ( 81.8:0
-----------------------------------1----------1----------1----------1----------1----------I----------I----------I-----------
PERSONS WITH NO DATA I O I O I O I O I O I O I I O
I C O.OXJ I C O. OXJ I I 0.0%1 I I 0.0%1 I I 0.0)() I I o.o:o I I I o.o;o
0
0
0:,
O'
OD
Table 2 (Contd)
RECONBINltlT HEPATIT I S 8 VACCINE
STUDY 0861
TREATl1ENT
LOT tM1BER CK564
DOSE 5 tlCG
PATIENT CLASS HEHOPHIU:ACS
I TOTAL VACCI HEES t lt PATlEHTSl - DOSE Z I

1----------------------------------------------------------------------------I
I DAY S POST VACCINATION • NU118ER
CLINICAL
Cot1PLAINTS
•----------------------------------------------------------------------------1
I O I l I 2 I 3 I ~ I 5 I
WITH
IC011PLAIHTS
••••••••••••••••••••••••••••••-•••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l•••••••••• l•••••••••••••a•••••••
• • I I I • I I
REACTION, LOCAL CINJECT. SITEI I l I O I D I D I O I D I I 1
I 1 1z.s1.1 I I 0.0%1 I I 0.01.1 I I 0.01.1 I , 0.0%1 I I o.0% 1 I I I 12.5%1
-----------------------------------1
SORENESS I----------1----------1----------1----------1----------1----------1----------1-----------
1 I O I O I D I D • 0 I I 1
I 1 12.s1.1 I r o.0%1 I I e.or.1 I l 0 . 0%1 I I o.o;o I • 0.0%1 I I c 12.5i0
-----------------------------------l----------l----------l----------l----------l----------l----------l----------l-----------
s 1sn111c I O I O I l I l I l I l I I l
I l O• 0% ) I l O. OY. I I l 12 • 5% I I( 12 • 5% I I C 12 • 51. I I C 12. 5% J I I I 12. 51.1
I I I
DIGESTI VE SYSTEH 0 0 1 l I l I l I I 1
0.0%1 0.0%) 12.5%1 12.s1.1 I r 12.SZI I r 12.5% 1 I I 1 12.s1.1
I I I I
DIARRHE A OI D I 11 11 11 11 I 1
I l 0 . 0%1 I c o.0%1 I I 12.s1.1 I I 12.s1.1 I r 12.5%1 I , 12.51.> I I 1 12 . s1. 1
-----------------------------------l----------l----------l----------l----------l----------1----------1----------1-----------
PERSONS WITH COt1PLAINTS I 1 I O I 1 I l I 1 I 1 I I 2
I I 12 . 51.I I c o.b%1 I I 12.5%1 I c 12.5%1 I r 12.5%1 I r 12.51.I I I c 25.01.1
-----------------------------------1----------1----------l----------l----------l----------l----------1----------I-----------
PERSOHS WITH HO COt1PLAINTS I 7 I a I 7 I 7 I 7 I 7 I I 6
I r a1.sx1 I 1100.0%1 I I e1 . 5%1 I c 87.5%1 I c &7.51.1 I r a1 . s1.1 I I 1 75.01.1
-----------------------------------1----------I----------I----------I----------I----------I----------I---------- I-----------
PERSOHS WITH 00 DAU I D I O I O I D I O I O I I 0
I I 0.0%1 I I o.o;o I I o.or.1 I l o.o;o I I o.o:o I I o.o;o I I c o.o:o
0
0
0,
c,.
-0
~
Table 2 (Contd)
PATIENT COUNT CLINICAL COt1PLAIHTS
RECott81HAHT HEPATITIS B VACCINE
STUDY 0861
TREATl1ENT
LOT HUl18ER CK56ft
OOSE 5 tfCG
PATIENT CLASS HEMOPHILIACS
I TOTAL VACCJNEES I 5 PATIENTS) - DOSE l I

l----------------------------------------------------------------------------1
CLINICAL
COflPLAIHTS
1----------------------------------------------------------------------------I
I O I 1 I 2 I 3 f lt I 5 I
MITH
IC011PLAJHTS
•••••••••••••••••••••••••••••••••••l•••••••••• l•••••••••• l••••••••••l••••••••••l•••••••••• l••••••••••l••••••••••I••••••••••
-----------------------------------l----------
PERSOt'5 WITH COt1PLAIHTS I O
l----------l----------l----------l----------l----------l----------1-----------
I O I O I O I O I O I I O
I I O. OZI I I O.OZ) I I O.OZI I I o . OZI I I O.OZI I I o . or.1 I I I o.or.1
-----------------------------------l----------
PERSOHS WITH NO COl1PlAINTS I 5
l----------l----------l----------l----------1----------1
I 5 I 5 I 5 I 5 I 5 I
----------1-----------
I 5
I ,~00.or.1 I 1100.or.1 I 1100 . or.1 I 1100.or.1 I 1100 . 021 I 1100 . or.1 I I 1100 . or.1
----------------- ------------------1----------I----------I----------I--- -------I----------I----------I----------I-----------
PERSONS WITH HO DATA I o I O I O I O I o. I O I I o
I I 0.01.1 I I 0.07.1 I I 0.07.) I I O,OZ) I C 0.07.) I I 0.01.) I I C 0.01.)
0
0
0,
--4
0
.,-
Table 3
PATIENT totffl CLINICAL COtlPLAIHTS
RECOt18111AtlT HEPATITIS 8 VACCINE
STUDY 0861
TRUTHENT
LOT NUIIBEA CK564
DOSE 10 HCG
PATIENT CLASS llEIIOPHILIACS
I TOTAL VACCIHEES t 3 PATlEHTSl - DOSE l I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I NUHSER
l----------------------------------------------------------------------------1
CLIHICAL
COMPLAINTS
,
................................... I•.........
I
O I 1
, I 2 I 3 I 4 I 5 I
..........•..........•..........•..........•..........•..........
I I • •
WITH
ICOt1PlAIHTS
..........
• I
,
I
REAcnot,, LOCAL IIHJECT. SITU I 1 I O I o I o I O I O I I 1
I I 33.3;1,) I f 0.0;1,J I I 0.0;1,J I I 0.0;1,) I I o.o;o I ( o.o;o I I ( 33.];1,J
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sOREIIEss I 1 I o I o I o I o ·I o I I 1
I 1 33_3;1,1 I , a.oio • , o.or.1 • c a.or., I , o.or.1 • , o.o;o • • c 33.lXJ
-----------------------------------•----------l----------1----------1----------1----------•----------•----------•-----------
SYSTEHIC I l I O I O I O I O I O I I 1
•• 33.3?.J I( a.or., I( 0.0;1,J I( o.or., I( 0.0?.I I( 0.0?.J I I I 33.3?.)
-------------------------------------------------------------------
1 I I I I I
WHOLE SOOY/GENERAL I 1 I O I o I O I O I O I I 1
I c 0.0;1,1 I f o.or.1 I c o.or.1 I I 0.01.1 I I 0.01.1 I
33.31.1 I 1 33.3?.I
I I I I I I I
SWEATING I 1 I o I o I o I o I o I I 1
I f 33.3?.I I f 0.0iO I I 0.0iO I I O.OY.I I I 0.0iO I I O.OY.I I I I 33,3?.I
-----------------------------------1----------l-------·--•----------l----------l----------1----------l----------l-----·-----
PERSOHS WITH CONPUIHTS I 2 I o I O I O I O I O I I 2
I , 66. 7Y., I f o. or., • t o. or.1 I c o. o:o I c o. ox I I , o. o;o I I 1 66. 7r.,
-----------------------------------1----------1----------1----------1----------I----------I----------I----------I-----------
PEASONS WITH HO COMPLAINTS I l I 3 I 3 I J I 'J I 3 I I 1
I I 33.lr.J I flOO.OXJ I 1100.0XI I ClOO.OXI I 1100.0XJ I 1100,0XJ I I I 33.lXI
-----------------------------------1----------1----------l----------1----------1----------l----------l----------•-----------
PERSOHS WITH NO DATA I D I 0 I 0 I D I 0 I o I I o
I I o.or.1 I I 0.0;1,J I C 0,0;1,J I( 0.0;1,J I I 0,0)() I I o.ox, I I I o.oxt
0
0
::»
....,
-
Table 3 (Contd)
PATIENT COUtlT CLINICAL COl1PU I NTS
RECIX181N.m T HEPATITIS 8 VACCIHE
STUbY 0861
TRE.lTttENT
LOT HUttBER CK564
DOSE 10 IICG
PATIENT CLASS: HEIIOPHILIACS
I TOTAL VACCIHEES I 3 PATJEHTSI - DOS£ 2 I

1---------------------------------------------------------------------------- I
I DAYS POST VACCINATION I HUMSER
CLINICAL
CONPLAIHTS
1-----------------------------------------------
I O I l I Z I J •
·---------------------------- 1 W
it • 5 I
ITH
ICOHPLAIHTS
••••••••••••••••••••••••••••••••••• l•••••••••• l•••••••••• l•••••••••• ••••••••••• l••••••••••l•••••••••• l•••••••••• I••••••••••
I I I I I I I I
REACTIO't, LOCAL (INJECT. SITE) I l I l I O I O I O I O I I l
I I 50.0)0 I C 50.0%) I I o.o;o I C 0 . 0%) I C o.o;o I I 0 . 07. ) I J C 50.07.1
-----------------------------------•----------1----------1----------1----------l---------- •----------l----------l -----------
soRENESS I l I 1 I o I o I O I o I I l
I c 5o . o;o I c 50.o:o I I o . o;o I c o.o;o I c o . o;o I c o.oz, I I , 50 . 01.1 .
----------------------------------- 1---------- I----------I----------I----------I----------I----------I----------I-----------
PERSotlS WITH COl1PLAIHTS I l I 1 I O I O I O I O I I 1
I c 50.o;o I c so.o;o I I o.o;o I c 0.0;:1 I c ,,. o;:1 I c 0.0%1 I I • so . oz,
-----------------------------------t---·------l----------l---------- t----------1---------- 1----------1--------· -1-----------
PERSONS W ITH NO COttPLAINTS I l I l I Z I Z • Z I Z I I l
I I 50.07.1 I I 50.0%) I uoo.o;o I (100.0%1 I 1100.07.) I fl00.07.) I I C 50.0i!)
----------------------------------- t---------- t---------- l----------l----------1----------1----------1---------- I-----------
PERSOHS W ITH NO DATA I O I O I O I O I O I O I I 0
I 1 0.0;:1 I c 0.0;:1 I 1 0.07.1 I c o.o;o I I o.ox 1 I c 0.0;: 1 I I • o.oY. 1
0
0
...
0,
•
Table 3 (Contd)
PATIENT COUNT CLINIC AL tottPLAI NTS
IIECOH8IIUHT HEPATITIS B VACCINE
SlUOY 01161
TRUTt1EITT
LOT 11Ut18ER CK5b4
DOSE 10 HCG
PATIENT CLASS HEHOl'lfIUACS
I TOTAL VACCINEES I l PATIENTSI - DOSE 3 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUtt8ER
1---------------------------------------------------------------------------- ••c0t1PLAJNTS
CLINICAL
·cOMPLAINTS
...................................,
I O I
,
1 I 2
, I :S • 4 • S I
-----------------------------------1----------l----------l----------l----------•----------l----------l----------
, ,WITH
•......... .......... .......... ,..........•..........•.......... .......... ..........
l-----------
slsTEMit I O • 1 • l I l I 1 I l I I l
I( o.ox, I ( 100.0XI I (100.0XI I 1100.0X) I (100.0X I I (100.0X) I I 1100.0X I
I
DIGESTIVE SYSTErt I O • l I l I l • 1 I l I I l
o.ox, I 1100.ox, • 1100.ox, • 1100 . ox, • 1100 . ox, I 1100.ox , I I 1100 .ox ,
I I I I I I I
GI BLEEDING I O I 1 I 1 I l I 1 I l • I l
I I O. DX I • 1100.0XI I 1100 . 0XI I 1100 . DXI I 1100.DXI I 1100.DXI • I 11D0.DXI
-----------------------------------1
PERSOHS WITH COttP U INTS I----------•----------
D • 1
l----------l----------l----------l----------•----------
I l I 1 I l I l •
I-----------
I 1
I I O.DXI • 1100.0XI I ClOO.OXI I 1100.0XI I 1100.0XI I 1100 . 0Xt I I 1100.0XI
-----------------------------------1I ----------l----------l----------•----------l----------
PERSOtts WITH NO COl1PLAINTS l • 0 I O • 0 I O
l----------•----------I-----------
I O • I O
I 1100.ox, • , o.ox, I I o.ox, • t o.o;o • 1 o.o;o I I o.ox , I I I o.o;o
-----------------------------------1----------•----------
PERSOHs WITH NO DATA I o I o II----------I----------I----------I----------I----------
o I o I o I o I
I-----------
I o
I I 0.07. 1 • I O.OXI I I O.OXI • I 0.07.I I I O.OXI I I 0.07. J • I I O.OXI
0
0
CD
....,
~
4'
Table 4
PATIENT COUNT HAXlt11JH TEtlPERATURES
RECOHBIHANT HEPATITIS B VACCINE
STU>Y 0861
TREATtlENT
LOT HUt1BER CK561rt
DOSE 5 NCG
PATIENT CLASS HEttOPHILIAC5
I TOTAL VACCIHEES I 12 PATIEHTSJ - DOSE 1 I

1•---------------------------------------------------------------------------------------I
OATS POST VACCINATION I HlR1BER
HAX TEHPER ATURE
I DE6 F , ORAL)
l---------------------------------------------------------------------------------------1
I D · • l I t • l I 4 I 5 I I
MITH
• HAX TEt1P
••••••••••••••••••••••••••••••••••••••••••••••• ••••••••••••••••••••••••••••••••l••••••••••l•••n•••••I•••••••••••~•••••••••
I I I • I • • •
< 99 • e • 6 I 7 • 7 I 7 I 7 I I 6
• uoo.o;o I I 75 . 0iO I ( 87.5?.I I ( 87.57.) I ( 87.57.1 I I 87.57.1 • I I 75.07.1
• I I I I I I I
99 - 99.9 I o I 2 I l I l I l I l I I 2
I I o.o;o I , 25.07.J I 1 1 2.5:1.1 I 1 12.51.1 I 1 1 2.51. 1 I 1 12.sx, • · I r 25.01.1
------------------------1I ----------1----------l----------
rEHPERATURE TAKEH a I 8 I 8
l----------l----------l----------l---------------------
I a I a I a I
l-----------
I e
I I 66.77.) I I 66.TI.I I ( 66.77.1 • I 66.77.) I I 66.77.1 I I 66.71.1 I I I 66.77.1
------------------------
nHPERATURE HOT TA'KEH
l----------l----------l----------l----------l----------l----------1
I " I ,. I 4 I ,. I ,. I " I
---------------------1-----------
I "
I I 33.37.1 I I 33.3%1 I I 33.3%1 I I 33.37.1 I I 33.31.1 I I 33.37.1 I I I 33.37.1
0
0
0)
....,
·-
~
•
Table 4 (Contd)
PATIENT COUNT HAXIt1UH 1£HPERATURES
RECOt181NAN1 HEPATITIS 8 VACCitlE
STUDY I 0861
TAEATHEHT
LOT NUl18ER I CK56lt
DOSE 5 HCG
PATIENT CLASS: HEttOPH ILIACS
I TOTAL VACCJNfES I 12 PATJEHTSI - DOSE 2 I

l---------------------------------------------------------------------------------------1
HAX TEMPmATURE
IDE& f , ORALI
l---------------------------------------------------------------------------------------1
I O I l I Z I 3 I It I 5 I I I HAMITH
X TEMP
••••••••••••••••••••••••l•-•••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 I 4 I It I l I J I It I 4 I I 2
I I eo . or. 1 I 1100 .0Y. I I l 60 . 07.1 I I 75.07.l I I 80,07.1 I I 80 . 07.1 I I l 40,07.1
I I I I I I I I
99 - 99.9 I 1 I o I 2 I 1 I 1 I 1 I I 3
I I 20,07. 1 I I 0.07. 1 I I 40 . 07. 1 I I 25.07. 1 I I 20.01.1 I I 20.01.1 I I I 60.07.1
------------------------1----------1----------I---------- I----------I----------I---------- I---------------------I-----------
TEHPERATUA E TAKEN I 5 I 4 I 5 I 4 I 5 I 5 I I 5
I C 41.7Y.t I t 33.37.1 I c 41.77.1 I I 3l.3Y. t I I ltl.77.1 I c ttl.77.1 I I I 41.77.1
------------------------1----------1----------I----------I----------I----------I---------- I--------------------- I-----------
TEHPERATURE NOT TAKEN I 7 I a I 7 I S I 7 I 7 I I 7
I C 58.31. 1 I c 66.71. 1 I l 58 . 31.1 I I 66.77.1 I t 58.37.1 I C 58.lY.I I I I 58.37. 1
0
C
...,
OIi
!JI
,#
Table 4 (Contd)
PATIENT COUNT HAXIt1U1 TEHPERAT\mES
RECOH8IHAHT HEPATITI S 8 VACCINE
STUDY 086 1
TRUTHENT
LOT NUttBER I CKS64
DOSE 5 NCG
PATlENT CLAss: HENOPHILJACS
• TOTAL Vl CtlNEES ( 5 Pl TIEHTSI - DOSE 3 •

1I ---------------------------------------------------------------------------------------•
DAYS POST Vl CCIHATlOH I HUl18ER
nAX TEt1PERATURE •--------------------------------------------------------------------- ------------------• WITH
I DE6 F , ORALI • D I l I 2 I J I 4 I 5 • • • HAX TEHP
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••• l•••••••••• I•••••••••••••••..••••••••••••••••••••••••••
I • I I I I I I
< 'i9 I 1 • l I l I l I l I l • I l
I 1100.0X I I 1100.0XJ I (100.0XJ • flOO.OXI I 1100.0Xl I ClOO.OX I I I 1100.0ZI
------------------------1----------1----------1----------1----------1----------1----------1---------------------1-----------
TEHPERATURE TAKEN • 1 I l I l I l • 1 • 1 • I l
• ( U. oz J I f 20. oz I I l to. oz I I ( 20. 01.) I I 20. OX ) I ( 20 . 01.) I • ( 20. 01. )
------------------------•----------
Tl ttPERATURE NOT TAKEN I 4
1I ----------1----------1
4 I 4 I
----------•----------1----------1
4 I 4 • 4 •
---------------------1• -----------
4
I , ao.o;o I I ao.o;o I , ao.ox1 I , ao.o;o • 1 eo . ox1 I , ao.ox1 • I I eo.ox1
0
0
_,
(J)
0-
,
Table S
PATIENT COUNT HAXIt1Ut'I TEt1PERATURES
RCC0t18IHAHT HEPATITIS 8 VACCilfE
STUDY 01161
TREATH£HT
LOT tM18ER CK564
DOSE UHCG
PATIENT CU SS HEHOPHilIACS
I TOTAL YACCINEES I J PATI ENTS) - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I NUHBER
HAX TEMPERATURE
IOE6 F, ORALI
1---------------------------------------------------------------------------------------I
I I I l I Z I 3 I ft I 5 I I I t1AXWITH
TE?1P
••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
< 99 I z I 2 I z I z I z I 1 I I z
I (100.0XI I 1100.01. 1 I ( 100.0X) I 1100.01.) I 1100.0XI I (100.0X ) I I (100.01. )
------------------------I----------
TEt1P£RATURE TAKEN I Z I
I----------I----------
2 I 2
I----------I----------
I 2 I 2
I----------
I 1
I--------------------- II-----------
I 2
I c 66.T/.l I c 66.71.1 I c 66.7i0 I c 66 . 7%1 I I 66.71.J I c 3J.3l0 I I c 66.7:0
------------------------l----------l----------1
n 11PERATURE HOT TAKEN I 1 I 1 I
----------l----------
1 I l
l----------1
I 1 I
----------1
Z I
---------------------l-----------
I l
I C 31.31. I I C 3J. J 1.J I C U.JX J I f 33. 37.1 I I U.JXI I f 66.T/. J I I ( 33.J:O
0
0
011
.....
.....
41
Table 5 (Contd)
PATIENT CCJUHT "AXI~ TEHPERAT\IRES
RECDt181HAHT HEPATITIS 8 VACCINE
STUOY I 081,l
TREATNEHT
LOT HUMBER CK56ft
[JOSE 10 HCG
PATIENT CLASS: HEl10PHILIACS
I TOTAL VACCIHEES t 3 PATIENTSI - DOSE 2 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCINATION • NUt18ER
" AX TE"PERATURE
(DEG F, «mALI
1---------------------------------------------------------------------------------------•
I 0 I 1 I Z I 3 I It I 5 I I I "AXWITH
TEHP
••••••••••••••••••••••••l•••••..•••••••••••••• l••••••••••l••••••••••l••••••••••l•••••••••••••••••••••l••••••-••I••••••••••
I I I I I I I I
< 99 I 1 I 2 I 2 I 2 I z I 2 I I 2
I uoo.o;o I 1100.0;0 I noo.o:o I n oo.o:o I 1100.01.1 I u oo.o:o I I uoo.01.1
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TE11PERATURE TAKEH I 1 I 2 I 2 I 2 I 2 I 2 I I 2
I ( 13.37.l I I 66. T/. l I ( 66. T/.1 I C 66. T/.J I C 66. Tl.t I C 66. Tl.I I I I 66. Tl. I
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TEl1PERATURE HOT TAKEN I 2 I 1 I 1 I 1 I l I 1 I I l
I C 66.T/.t I ( .J3.V.I I C 13.37.1 I I 33.37.1 I I 33.3)0 I f 33.3:1.1 I I I 33 .3:1. t
0
0
OIi
.-
"
CD
NONRESPONDERS/
HY PORES PONDERS
008H
SUMMARY - NONRESPONDERS. HYPORESPONDERS AND TRANSIENT RESPONDERS
Non responders
A total of 81 persons, all of whom failed to develop antibody after rece1v1ng

three injections of plasma-derived hepatitis B vaccine, have received one or
more injections of yeast recombinant vaccine in six studies. This population
includes both healthy adults and patients with chronic renal insufficiency who
are receiving dialysis treatment (dialysis patients) . Healthy adults receive
three 10 mcg doses and dialysis patients receive three 20 rncg or 40 mcg doses
of yeast recombinant vaccine at 0, l, and 6 months.
Fifty-five healthy adults have received one or more 10 mcg doses of yeast
recombinant vaccine. Twenty-four persons have completed the three injection
regimen. At 7-9 months, 79% (11/14) seroconverted (S/N ~2.1) and 50% (7/14)
developed protective levels of antibody (mIU/ml ~10), Geometric mean titers
among responders with a titer of S/N ~10 or mIU/ml ~10 were 39.3 S/N and 245.1
mIU/ml in each of the two studies where such data are available.
Twenty-sh: dialysis patients have received an initial injection of vaccine.

Twenty-one of these received a 40 mcg dose and five received a 20 mcg dose.
Six participants have received three injections of vaccine. At 2-3 months,
25% (1/4) and 35% (6/17) have titers of S/N ~2.1 after two 20 or 40 mcg doses
of vaccine. respectively. Protective levels of antibody developed in 251 (20
mcg dose) and 18% (40 mcg dose). Geometric mean titers among responders with
an antibody level of ~IU/ml ~10 were 53.0 mIU/ml (20 mcg dose) and 43.2 mIU/ml
(40 mcg dose). · At 7-8 months the single individual measured after three 20
mcg doses and one of three persons monitored after three 40 mcg doses have
protective levels of antibody (mIU/ml ~10). These two responders had titers
of 136.9 mlU/ml (20 rncg dose) and 49.4 mIU/ml (40 mcg dose).
Two hemodfalysis patients withdrew from a study due to clinical complaints

which were considered possibly related to vaccine. A 32-year old subject
developed a swollen, stiff and sore left arm after adainistration of vaccine.
The symptoms persisted for one week and then subsided. A 72-year old male
subject developed generalized ach1ness and a headache three days after
administration of the first injection of vaccine. Forty-eight hours after
onset of these symptoms, he developed a flu-like syndrome with a temperature
of 1oo•F. He did not receive any further vaccine injections.
Hyporesponders and Transient Responders
Two hyporesponders and three transient responders to plasma-derived hepatitis

B vaccine have received a single 10 mcg dose of yeast recombinant vaccine. No
serious or alarming adverse reactions attributable to vaccine have been
reported.
3171 I/1
1 /21 /86
00880
Hyporesponders and Transient Responders (Cont.)

At one month post-vaccination, one hyporesponder displayed a marked boost in
HBs antibody. A protective level of antibody has been maintained over 6
months of follow-up in this individual. The other individual has not
responded to the vaccine. One month after vaccination, 100% (2/2) of
transient responders have protective levels of antibody with a geometric mean
titer of 67.9 mIU/ml.
31711/2
1/21/86
00881
NONRESPONDERS. HYPORESPONOERS AND TRANSIENT RESPONDERS
Study 794 - Bethesda, MD - Dr. H. Alter

The study population consists of seronegative nonresponders to plasma-derived
vaccine and health care personnel who have not previously received any
hepatitis B vaccine. Health care personnel receive either 5 mcg of 10 mcg
injections of vaccine and nonresponders receive 10 mcg injections. All
participants are administered vaccine lot C-K444 at 0, 1, and 6 months.
Eleven nonresponders have received two 10 mcg injections of vaccine and eight
of these have received the third dose. At 7/8 months, 88% (7/8) of the
participants seroconverted (S/N ~2.1) and 63% (5/8) developed protective
levels of anti-HBs (S/N ~10). The GMT at that time for all vaccinees was 25.0
S/N and 95.9 for responders (S/N ~10).
No serious or alarming adverse reactions attributable to vaccine have been
reported. The study continues in progress. Refer to the sunmary on health
care personnel/healthy adults for data regarding other subjects vaccinated in
this study.
Study 816 - Philadelphia. PA - Dr. S. Plotkin and Or. S. Starr

The study population consists of three groups of adults negative for hepatitis
B serologic markers: hemodialysis patients, health care personnel, and
hemodialys1s patients who were nonresponders to plasma-derived vaccine.
Nonresponders receive 20 mcg or 40 mcg injections of vaccine lot C-K444 at O,
1, and 6 months.
Five nonresponders have received two 20 mcg injections of vaccine and three of
these have rtce1ved the th1 rd injection. Serology data at 7/8 months is
available for one vacc1nee only. This subject seroconverted (S/N ~2.1) and
developed protective levels of anti-HBs (mIU/ml ~10) with a titer of 136.9
mIU/ml.
Four nonresponders have received t wo 40 mcg injections of vaccine. Three of
these have received the third injection. Seven/eight 1110nth serology data are
available for three vaccine recipients. One (331 ) of the subjects
seroconverted (S/N ~2.1) and developed protective levels of anti-HBs (mIU/ml)
at that tinie. The GMT for all vaccinees was 2.1 mIU/ml and 49.4 for
responders (mIU/•1 ~10).
No serious or alarming reactions attributable to vacc1ne have been reported.
The study continues in progress. Refer to the sunmaries on health care
personnel/healthy adults and dialysis patients for data regarding other
Study 817 - est Point , PA - Or. R. Bishop

Preinmune healthy adults and nonresponders to plasnia-derived vaccine are
enrolled in Study 817. Preinnnune adults receive a single 10 mcg injection of
3160I/1
00882
Study 817 - West Point, PA - Or. R. Bishop (Cont.)

vaccine. Nonresponders receive 10 mcg injections of vaccine lot C-K444 at o,
1 , and & months.
Four nonresponders have received two 10 mcg injections of vaccine and three of
these have received the third injection. Serology data are available for two
of the vaccinees at 7/8 months. Neither participant seroconverted for
anti-HBs at that time.
reported. The study continues in progress. Refer to the su11111ary on preimmune
adults for data regarding other subjects vaccinated in this study.
Study 854 - Boston, MA - Dr. J. Oienstag

The population of Study 854 cons hts of four groups: chronic carriers of
HBsAg., and healthy hypo responders, non responders, and transient responders to
plasma-derived hepatitis B vaccine. Hyporesponders and transient ·responders
receive a single 10 mcg injection of vaccine lot C-K564. Nonresponders
receive 10 mcg injections of the same vaccine lot at 0, 1, and 6 months.
Two hyporesponders have received a 10 mcg injection of vaccine. One of the
vaccinees displayed a raarked boost in anti-HBs titer one month after receiving
vaccine. The other participant has not responded.
Three transient responders have received a 10 mcg injection of vaccine. At
one month, two out of the three (67%) transient responders who were
seronegative for anti-HBs prior to vaccination, seroconverted for ant1-H8s.
The GMT for the two responders was 67.9 mIU/ml.
Fourteen nonresponders have received one 10 mcg injection of vaccine and
thirteen of these have been administered the second and th1 rd injections. · At
6 months, 58% (7/12) of the subjects seroconverted for anti-HBs (S/N ~2.1) and
251 (3/12) developed protective levels of ant1-HBs (mlU/ml ~10). The GMT for
all vaccinees at 6 months was 3.2 mIU/ml and 45.8 for responders (mIU/ml ~10).
reported. The study continues in progress. Refer to the sunmary on chronic
carriers for data regarding other subjects vaccinated in this study.
Study 874 - Pasadena, CA - Dr. M. Tong

Healthy adults who were nonresponders or hyporesponders to plasma-derived
hepatitis B vaccine are enrolled in the study. All participants receive 10
mcg injections of vaccine lot C-K563 at 0, 1, and 6 months.
Twenty-six non responders and hyporesponders have received two 10 mcg
injections of vaccine. None have received the third injection. At one 1110nth,
36% (9/25) of the vacc1nees seroconverted for anti-HBs (S/N ~2.1). Further
serologic data are not currently available.
31601/2
00883
Study 874 - Pasadena, CA - Dr.~- Tong (Cont.)

No serious or alarming adverse events · attributable to vaccine have been
Study 875 - Duluth, MN - Dr. T. Johnson

The study population consists of adult hemodialysis patients ~ho were
nonresponders to plasma-derived hepatitis B vaccine. Participants received 40
mcg injections of either yeast recombinant vaccine lot C-K937 or
plasma-derived vaccine lot 2277K at 0, l, and 6 months.
Seventeen nonresponders have received one 40 mcg injection of yeast
recOllb1nant vaccine and fifteen of these have been administered the second
injection. ~one have yet received the third injection. Two month serology
data are available for 13 redpients of yeast recombinant vaccine.
Thirty-eight percent (5/13) seroconverted for ant1-HBs (S/N ~2.l) and 151
(2/13) developed protective levels of anti-HBs (11IU/ml ~10). The GMT for
responders was 70.7 (mIU/ml ~10).
Eighteen nonresponders have received one 40 rncg injection of plasma-derived
vaccine. Seventeen of these have received the second injection and none have
received the third. At 2 months, 40% (7/15) of the plasma-derived vaccine
recipients seroconverted (S/N ~2.1) and developed protective levels of
anti-HBs (mIU/ml ~10). The GMT for responders was 131.6 (mIU/ml .~10).
Two subjects experienced adverse experiences which were considered possibly
related to vaccine. A 32-year old male hemodialysis pati_ent received a 20 111cg
intramuscular injection of vaccine into each deltoid (total dose 40 mcg). The
patient's left am subsequently became swollen, stiff and sore. These
symptoms persisted for one week and then subsided. The patient did not
receive any further vaccine injections. A 72-year old male hemodialysts
patient developed generalized achiness and a headache three days after
administration of the first injection of vaccine. Forty-eight hours after
onset of these symptoms, he developed a flu-like syndrome with a temperature
of lOO•f. The patient did not receive any further vaccine injections. -
31601/3
1/21/86
Study 794
00884
PROGRAM: Yeast Recombinant Hepatit1s B vacc1ne, Study 794

vaccine among:
1. Hea 1th care personnel immunized w1th plasma
der1 ved vaccine who were nonresponders ( ant1-HBs
negative).
VACCINE: Yeast Recombinant Hepatitis 8 Vaccine:

Lot '972/C-K444 (10 mcg/HBsAg ml)
PRIMARY Harvey J. Alter, M.D.

INVESTIGATOR: Chief, Innunology Section
Bethesda, Maryland
SECONDARY David Henderson, M.D.

INV ES TI GA TORS: James Schmitt, M.D.
Ms. Deloris Koziol
Ms. Beverly Elder
STUDY LOCATION: Clinical Center Blood Bank

National Institute of Health

are negative for HBsAG, anti-HBc and ant1-HBs, have a
nomal ALT level and have not previously received any
hepatitis B vaccine. It also includes 11
nonresponders to plasma-derived vaccine.
32251/1
l /20/86
00885
Study 794
PROCEDURE: Health care workers receive either 5 mcg or 10 mcg

doses of vaccine at 0, 1 and 6 months. Nonresponders
receive 10 mcg doses at 0, l and 6 months. A11
injections are intramuscular. Participants are asked
to record their temperature for 5 days after each
injection and note any local or systemic reactions.
Blood specimens are obtained prior to vaccination, and
monthly for 7 months and at 9, 12 and 24 months post
inith,1 injection. All sa...,les are assayed for
ant i-HBs, ant 1-HBc, and HBsAg and ALT by Dr. Alter.
Sa11p1es with anti-HBs titers ?:,25 mIU/111 may be tested
for anti-! and ant1-g_ activity at SDRL.
RESULTS: NONRESPONDERS TO PLASMA VACCINE

10 mcg Lot 972/C-K444 at 0, land 6 months
Injection No.
Dose Level _l_ _2_ ..l...
10 mcg 11 11 8
2. serologic Results:
participants at 7/8 months. Seroconversion was
88% ( 7/8) when the cutoff was S/N ~2 .1. When the
cutoff was S/N ?:,10, seroconverston was 63% (5/8).
The GMT for all vaccinees was 25.0. Table 1 shows
anti-HBs responses through 12 months of follow-up.
32251/2
1 /17/86
00886
Study 794

and 8 vaccinees fol lowing 1nject1ons one, two and
three, respectively. Listings of specific
complaints and maximum temperatures reported
during the five days of follow-up after each
injection are provided in Tables 2 and 3.
Dose f. in 'I, by lnKtion Ng.

Type of C(!!plaint Level _1_ 2 _3_
Injection Siu 10 IIC9 9(1/11) 0(0/10) 25(2/8)
Systemic 10 llC9 18(2/11) 10(1110) 0(0/8)

reactions attributable to vaccinat\on.
32251/3
1/20/86
Table 1
AHTIBODY RESPONSES FOLLOl41HG VACCINATION WITH RECOHBINAHT HEPATITIS B VACCINE
STUDY 07'1't
POPULATION HONRESPOHO~S ( H)
DOSE 10 NCG
LOT CK444
REGIHEN O, 1, ANO 6 HONTHS
I ~ WITH AHTI-HBS I 611T IS/Ml I

Il---------------------------------------l-----------------------------------------------------1
I I l!ESPONOf:l!S I
TINE
ll10HTHSl Il---------------------------------------1-----------------l-----------------------------------1
SIN>= 2.1 I SIN>= 10 I All VACCIHEES I S/N >= 2.1 I S/H >= 10 I
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••ww•••••••w•••••••••••~
I
1 NOHTH I 45)! (S/111 I 18Z (2/11 I 3.1 11.1 52.6 I
I
2 HONTHS I ssx 16/lll I 18:'. (2/111 4.7 15.8 114.2 I
I I
3 MONTHS I 781. 17/9) I 33r. 13/91 8.0 14.1 60.3 I
I I I
(, HOHTHS I 60)! 13/Sl I 60:'. 13/51 12.3 61.5 61.5 I
I I I
7/8 t!OtlTHS I 88¼ (7/81 I 63r. (S/81 25.0 n.o 95.9 I
I I
9 HOHTHS I eor. (4/51 I 60Z (3/51 lZ.9 23.8 39.3 I
I I I
1Z t10HTIIS I 60r. (:Y51 I 40Z (2/51 &.2 31.3 55.9 I
I
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
0
0
~
011
.....,
Table 2
PATIENT COlMT CLINICAL COt1PLAINTS
RECOt'eIHAHT HEPATITJS 8 VACCINE
STUDY . • 117"-
TREATH£HT
LOT tM18ER CK44,.
DOSE 1 10 t1t6
PATIENT CUSS: flOHRESPOtfflERS (HJ
I TOTAL VACCINEES I 11 PATIEHTSI - OOSE 1 I

1I ----------------------------------------------------------------------------I
DAYS POST VACCINATION I HUffllER
CLINICAL
COHPUINTS
l----------------------------------------------------------------------------1
I 0 • 1 • Z • J • 4 • S •
WITH
•c0f1PUINTS
e•••••••••••••••••••••••••••..•••••••••••••••I••..••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
AUCTION, LOCAL UHJECT. SITU •• 1 •I O •I O •I O •I O II O II •I 1
I I 9.17.J I I o.o:o I I o.o:o I I o.ox, • I o.o:o • I O.OiO I I I 9,liO
-----------------------------------
!OIIENns
1----------l----------
I 1 I o I
l----------
o •
l----------
o I
l----------
o I
l----------l----------
o I
l-----------
I 1
• r 9.17.J 1 I 0 .07.J I I 0.07.J I I 0,07.J • I 0.07.I. I 0.07.1 I I I 9.17.I
-----------------------------------1----------•----------•-
SYSTEHIC I 0 I l I
·--------l----------1----------1----------
1 I O • 0 I O
l----------•-----------
• • Z
•, o.ox, I , ,.1x1 I , , .1x, • 1 o.ox, I , 0.01.1 • r 0.01.1 I Ir 1a.21.1
------------------------------------
AESPIRATORT 1
I (
' 0
0.07.J
I
I I
O
o.o;o •
•
I
1
,.1:0 • I
I O I O •
0.07.J • ( . 0.01.1 • I
0
o,o;o I
I I
• (
l
9.liO
I
UPPER RESPIRATO!n INFECT.• HOS I 0 I• 0
•
• 1 •
I
0
•
• 0
•
• 0 •
I
I• l
I I 0,0XI I I 0,07.I I I 9.17.1 I I 0 .0X I I I 0.07.1. I 0.07.J. • I 9.11.J
I I I I I I • I
MUSCULOS!C.ELETAL I o I 1 • 0 • 0 • 0 I O I • l
• I o. ox, I I 9.17.1 I I o.or., I I 0. 01.1 • I 0 ,01.J • I o .o;o • I 1 9.17.J
ARTHRALGIA, t10HOARTICULAR •• 0 •• 1 II O I• D •• 0 I• O •• I• 1
• I 0 .01., • I 9.17.J • ( o.o;o I I 0.01.J • ( 0,01.I • ( 0.OlO I • ( 9. 17. 1
-----------------------------------•----------l----------1
PERSONS MITH COf1PLAIHTS I 1 I 1 I
----------1
1 I
----------1----------•----------l----------•-----------
O I O • O • • J
I I 9.11.1 I I 9.17.1 • I 9,1)0 I I 0.OXI I ( 0.07.1 • I 0. 07. J I I ( 1!7.31.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS NJTH NO COl1PLAINTS I 10 I 10 I 10 I 11 I 11 f 11 I I 8
I c 90.97.J I c 90,97.J I c 90.9i0 I noo.ox, I noo.oiO I 1100.0:0 I I I 72.77.J
-----------------------------------1I ----------•----------•----------•----------
PEASONS MITH NO DATA 0 I o I 0 I 0
l----------•----------•----------•-----------
I 0 I 0 I I o
• I 0.0XJ • C o.o;o • C , .ox, I I t .Oi!I I I 0.01.) • I 0. 01.I I • I. 0.0iO
0
0
0,
0,
0,
Table 2 (cont.)
PATIENT COUNT CLINICAL CONPLAIHTS
REC0t18IHAHT HEPATITIS B VACCINE
STUDT 07~
TREATMENT
LOT HUMBER CK444
DOSE 10 t1CG
PATIENT CLAS!I: NOtfRESPOHD!RS (HJ
I TOTAL VACCIHEES ( 11 PATIENTS) - DOSE 2 I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATI0!-1 I •NUl1BER
CLINICAL 1----------------------------------------------------------------------------• WITH
Cot1PlllNTS I O I
, 1 I
,2 I 3
, • , • 5 • ICOttPUINTS
.............................................. .......... .......... ..........•..........•..........•..........•..........
-----------------------------------1----------1----------•----------I----------•----------•---------- ----------•-----------
srsTE11IC • 0 I 1 I D I O • 0 I O • 1
I ( D.07.1 I ( 10.0ZI I ( 0.07.I I ( 0.07.1 I ( 0.0XJ I ( o.o:o I ( 10.0;0
WffOLE IIOOTIGENEHL • 0 I 1 I O I O I O • 0 • 1
0.0ZI I ( 10.0XI • ( o.ox, I ( 0.07.) • ( o.ox, • ( o.ox, I ( 10.0XJ
I I I • I •
CHILLS I O I 1 I O I o I o • o • l
c o.ox, I c 10.0,0 I c o.o;o • c o.ox, I c o.ox, I c o.o;o I c 10.0,:1
I I I I • I
DIGESTIVE STSTEH I O • 1 I 11 • II I O • 0 I 1
o.o;o • ( 10.0XI • ( o.ox, I ( o.ox, I ( II.OZ) I ( 0.0XI • ( 111.0;0
NAUSEA I 0 •I 1 II 0 •I 0 •I 0 •I 0 •I 1
I , o.ox, I c 10.ox, I I o.ox, I c 0.01., I c o.o::o • c o.ox, I c 10.0,:1
-----------------------------------1----------•----------l----------l----------l----------l----------l----------•-----------
PERSONS Miffl ~Of'IPLAIHTS I O I 1 I o I O • o I O I I 1
I ( a.ox, I ( 10.ox, I ( o.o::o I ( 0.01.1 • ( o.o;o • I 0.0XI • • C 10.01.I
-----------------------------------1----------I----------I----------I----------I----------I---------- I----------I-----------
PtRsom WITH HO COMPLAINTS I 10 I , I 10 I 10 I 10 I , I • ,
I 1100.ox, I , ,o.oz, I uoo.01.1 I 1100.ox, I 1100.ox1 I 1100.ox, I I c 90.ox1
-----------------------------------1----------l----------l----------l----------•----------•----------•----------I-----------
PtRsoos WITH HO DATA I O • 0 • 0 I O • 0 • 0 • I 0
• I o.o;o I { 0.07.1 • { 0.01.1 I I 0.01.1 • ( 0.07.) I C o.o::o I • I 0.0ZI
0
0
011
a,
-0
Table 2 {cont.)
PATIENT COUNT CLINICAL CUl1PLAINTS
RECOMBJNANT HEPATIT~S 8 VACCIN£
STWT 0 794
TREAfflEHT
LOT IU'IBER I CKft'i4
DOSE 10 ffl:6
PATIENT CLASS: NOtlRESPOtlDERS CIO
------------------------------------------------------------------------------~---------------------------------------------
I TOTAL VACCIHEES l 8 PATI ENTS I - DOSE 3 I
1I----------------------------------------------------------------------------
I• N\JfBER
1• ----------------------------------------------------------------------------I
CLINICAL
COt1PLAIHTS 0 I
••
1 I
II
2 I
••
3 • 4 • 5 I
......................................................... ....................................................... ..........
•I
WITH
,
•cOHPLAIHTS
RE ACTION, LOCAL IINJECT. SITEI 2 1 l o •I O •I O •I II 2

I C ZS.0lO • l 12.57.J • ( 12.s:o I C o.o:o • ( 0.07.J • I o.o:o I I ( 2s.o;o
-----------------------------------
SORENESS
1I ----------l----------
2 • 1
l----------l----------l----------
• 1 I O I O I•----------•----------
O I II-----------
2
I • 2s.o;., I • 12.s;o I < 12.s:o I • o.o:o • • o.o;o I I o.o;o I I c zs.o:o
-----------------------------------1
PERstim MITH COHPLA INTS I
----------
2
I----------
• 1
I----------I----------I----------
• 1 • O I O
I----------
• 0
I---------- I-----------
• • 2
• • zs . o;. , • • 12.s1., I c 12.s?.1 I f o.o;o I c 0.0;.1 • • , .or. 1 I • c zs.o:o
-----------------------------------
PERSONS Wiffl NO COt1PUINT9
•----------1
• 6 •
----------1----------1
7 • 7 •
----------1----------1----------
8 I 8 I 8
•---.
•
______ I,__________
6
_
I c 79 .0Y. J I • 87. !JY.l I c e1.sr. 1 I 1100.01.1 • noo.or., • 1100.0?.1 I I < 75 .o:o
-----------------------------------1
PERSONS MI TH NO DATA I ----------l----------
O I O Il----------•----------l----------•----------l----------•-----------
O I O • 0 • O I I O
• ( 0.07. J I I 0,07.) I l 0 ,07.J I C o.or., • C 0.07.J I l o.or. , • I I o.or.,
0
0
OD
"'
0
Table 3
PATIENT COUNT NlXlt1U'I TENPERAT\JRES
RECot18lHANT HEPATITJS 8 VACCINE
STUJT : 0794
TREATHEHT
LOT t-AJneER CK4ltlt
OOSE 10 t1C6
PATIENT CUSS NONRESPOtlJEAS IHI
I TOTAL VACCINEES I 11 PATIENTS) - OOSE l I

1---------------------------------------------------------------------------------------I
I OATS POST Vl CCIHl TION I HlnlEA
NlX TEffl'ERAlVIIE
IDE6f,ORlLI
1
I --------------------------------------------------------------------------------------I
II I 1 I 2 I 3 I It I 5 I I WITH
IHAXTEHP
•••••••••••••••••••••..••••••••••••l•-•••n•••l••••••••••l•..••••••••••••••••••••..••••••• l••••••••••l••••••••••l••••••••n•
NORML
•I I 1
9.11.)
I
I I
l
9.un •I 1 l I l I l I l I
9.11.1 I I 10.0Y.I I I 11.liO I I 11.lY.I I
I
I I
l
9.lY.I
I I I I I I I I
< 99 I 8 I 8 I 8 I 8 I 6 I 7 I I 7
I 1 12.11.1 I 1 12.1:0 I 1 12 . 11., I I ao.01.1 I 1 66.77.1 I I 11.a;o I I 1 63.6iO
I I I I I I I I
99 - 99.9 I l I z I z I 0 I z I l I I 2
9.11., I , 1e.z:o I I ut.27.1 I c 0.01.1 I c 22.21.1 I c 11.11.1 I I I 18 .21.I
I I I I I
100 - 100.9 I •
0.07.1
I
I C
0
0.01.1
I
I C •
o.01.J
I
I
1
C 10.01.J
I 0
I C o.or.1
I
I 1
0
0.01.,
I
I
I
I I
0
o.o;o
102 - 102.9 I 1 I o I o I o I o I o I I 1
I I 9.11.J I C 0.01.1 I C 0.01.1 I I 0.01.1 I c 0.01.1 I I 0.01.1 I I I 9,11.1
------------------------ l----------l----------l----------l----------l----------l----------1---------------------1-----------
TENPERATURE TAKEN I 11 I 11 I 11 I 10 I 9 I 9 I I 11
I 1100.01.1 I noo.or., I Cl00.07.l I C ,o.,r., I I 81.81.1 I I 81,87.l I I noo.or.1
------------------------1----------1----------l----------t----------l----------l----------l---------------------l-----------
TENPERATURE HOT TAKEN I t I O I O I l I 2 I 2 I I 0
I I 9.07.J I I 0.01.:1 I c 0.01., I I 9.17.1 I c 18.27.1 I I 18.27.J I I c 0.01.1
0
0
OD
....-c
Table 3 (ront.)
PATIENT COtMT nAXIl1Utt TEflPERAT\JRES
RECOt1BlHANT HEPATITJS B VACCIHE
STUOY 0794
TRU'fflENT
lOT NUIIBER r CK444
IIOSE IO t1C6
PATUNT CLASS: NONRESPONllER!I (HI
I TOTAL VACC:INEES I 11 PATIENTS) - DOSE Z I

Il---------------------------------------------------------------------------------------1
DAYS POST VACCINATION I HUHIIER
MX Ttl1PERATWE
I DES F, ORAL l
1---------------------------------------------------------------------------------------I
I O I l I Z I 3 I 4 I S I I
Wint
I t1A)( TEHP
-•••••••••••••••••••••••••••••..••••••••••••••••••••••.. ••••••••••••••••••••••••••••••••••••••~•••••l••••••••••I••••••••••
Hm!l1AL I 1 I 1 I 1 I 1 1 I l I I 1
I I 11.liO I ( 10,0lO I l 10,0lO I I 11,ll'.) I• I 14,31.1 I l 14.31.1 I I , 10.or.1
I I I I I I I I
< 99 I 7 I 7 I e I 7 I 5 I s I I 7
77.91.) I I 70.01.) I I eo.or., I I 77.er., I C 71.41.) I ( 71.4,o I I I 10.0;0
I I I I I I I
99 - 99.9 I 0 I z I 1 I 1 I 1 I 1 I I 1
o.or., I ( 20.0Y.I I ( 10.or., I ( 11.11., I ( 14.31.1 I ( 1•.31.l I I f 10.01.l
100 - 100. 9 I 1 I o I o I o I o I o I I l
I c 11.ir.1 I I o.or., I r o.oio I c o.or., I t o.or., I I o.o;o I I c 10.0;0
------------------------1----------1----------1----------1----------1----------1----------1---------------------1-----------
TEt11'tRAl\lRE TAKEN I 9 I 10 I 10 I 9 I 7 I 7 I I 10
I I 81.8)0 I C 90.9)0 I I 90.9)0 I ( 81.a:o I l 63.6:1.I I ( 6].6i0 I I C 90.9i0
------------------------1----------1----------1----------1----------1----------1----------1---------------------1-----------
TEHl'tRATtJRE HOT TAKEN I Z f 1 I 1 I Z I 4 I 4 I I 1
I I 18.21.I I C 9.lY.l I l 9.llO I I 18.ZY.J I ( 36.4Y.J I ( 36.4i0 I I l 9.lY.I
0
0
CJ)
,0
"'
Table 3 (oont.)
PATIENT COUNT tlAXIMUn TEl'IPERATUl!ES
RECOttBINANT HEPATITJS 8 VACCINE
STUDY l 07~
TIIEATHEHT
LOT Nllt'BER CK444
DOSE 10 11CG
PATIENT ClASSt HONRESPOHDERS IH t
• TOTAL VACCIHEES ( 8 PATIENTS) - DOSE 3 I

•---------------------------------------------------------------------------------------
• DAYS POST VACCINATION •• NUt19ER
nAX TEMPERATURE
IDE& F,ORALJ
•---------------------------------------------------------------------------------------1
• 0 • l • 2 I 3 I 4 I 5 • I WITH
.t1AXTEHP
.................................................................... ,..................... l••······••I••········•··········
I • I • I • . I I
NORMAL • JI 41 SI
,1 SI SI I l
I , 31.s;o t I so.o;o I • so.ox, • • 62.s:o I I u.s,o I • 62.sx, I • 1 n.sx,
I I I I I I I I
< 99 I s I 4 I , • J I 3 I J • I s
• ( 62.s:o I ( 50. 0Y. ) I I so.o:o I f 37.57.) I I 37.SiO I ( 37.SiO I I I 62.SlO
------------------------•----------•----------l----------•----------l----------1----------1
TEHPERATURE TAKEN • a • a I a I a I a I a I
---------------------•-----------
I a
I noo.o;o • uoo.o;o I uoo.o;o • noo.o;o I uoo.o:o • uoo.o;o I • noo.o;o
------------------------•----------•----------1----------•----------•----------•----------•---------------------•-----------
TEHPERAT\JRE HOT TAKEN • 0 I O I O I O • 0 I O I I O
I I 1 ,07.1 I I 0.07.) I I 0.07.t I ( 0.07.) I ( 0.07.) I I O.OY.) I I I 0.07.)
0
0
OD
,G
v,I
Study 816
ooflqil

Study 816

serologic markers.
2. health c&re personnel negative for hepatitis B
serologic markers.
(anti-HBs negative).

PRIMARY Stanley Plotkin, M.0./Stuart Starr, M.D.

34 Street and Civic Center Boulevard

Allentown, Pennsylvania 18104
Dialysis, Inc.
1230 Bunnont Road
Downingtown, Pennsylvania 19335
25391/1
l /21 /86
ooeqs
Study 816

dialysis patients {including previous nonresponders
to plasma-derived vaccine), and 20-25 health care
personnel, of either sex (excluding pregnant women).
who are negative for HBsAg, anti-HBc and ant1-HBs,
and have a nonnal ALT level. D1a1ys1s patients
(excluding nonresponders to plasma-derived vaccine)
received any hepatitis 8 vaccine.

Dialysis patients receive 1.0 ml (20 mcg HBsAg) or 2
x 1.0 ml (40 mcg HBsAg) intramuscular 1nject1ons of
vaccine at O, l, and 6 months. Health care
personnel receive 0.5 ml (10 mcg HBsAg)
intramuscular injections of vaccine according to the
participant approximately two weeks before the
first injection of vaccine. Post-vaccination blood
samples are obtained at 1, 3, 6, 8, 12 and 24
months.
anti-HBc, and ALT. Samples may be tested for yeast.
antibody. In addition, saq,les with an ant1-H8s
titer? 25 mIU/ml niay be tested to detennine anti-!
and anti-~ subtype specificity.
25391/2
1 /21 /86
Study 816
RESULTS: NONRESPONDERS (DIALYSIS PATIENTS)

Dose Injection Nu111ber

im£.9l
20 s 5 3
40 4 4 3
Serologic data at 7/8 months are available for
four dialysis patients who were nonresponders to
the plasma-derived vaccine.
At 7/8 and 12 months, anti -Hes responses are as
follows:
6"T (aIIJ/llll l
Tille ~ POsitiva &nti-MBs All - rs
(fblths) (mcg) S/N ~2. 1 IIIIIU/111 ~10 vaccinees SIil ~2.1 mIU/1111 ~1(
-
7/8 20 100(1/1) 100(1/1) 136.9 136.9 136.9
40 33(1/3) 33(1/3) 2.1 49.4 49.4
12 20 50(1/2) 50( 1/2) 3.4 38.S 38.5

40 67(2/3) 33( 1/3) 3.0 9.3 22.3
Anti-HBs responses at 1 through 12 months are

Clinical follow-up data are available for 3 (20
mcg dose) and 4 (40 mcg dose) dialysis patients who
25391/3
1/21 /86
ooecn
Study 816
RESULTS (CONT.): were nonresponders to the plasma-derived vaccine

following the first injection of vaccine: for 4
dialysis patients following· the second 20 or 40
mcg dose and for 3 dialysis patients following the
third 20 or 40 IIIC9 dose of vaccine.
Clinical complaints and maximum temperatures
reported following each injection are provided in
Tables 2-5. In SUlll'flary:
Clinical Dose % Frequency by Injection Number
Complaint 1mill 1 2 3
Inject ion 20 0 (0/3) 0 (0/4) 0 (0/3)
Site 40 0 (0/4) 0 (0/4) 0 (0/3)
Systemic 20 0 (0/3) 0 (0/4) 0 (0/3)
40 0 (0/4) 0 (0/4) 0 (0/3)
Ho serious or alarming adverse reactions

(15) (6)
1. A 53-year old female subject, case no. had a
history of hypertension, diabetes mell1tus,
cirrhosis, severe renal osteodystrophy and
end-stage renal disease (Jx/week he110d1alys1s).
Approximately five months after receiving a second
20 mcg dose of recombinant hepatitis B vaccine lot
974/C-K446, she died due to congestive heart
failure, renal failure, and severe
arteriosclerosis. The investigator does not
consider the death to be related to vaccination.
2. A 63-year old male dialysis patient, case no. (o) o)
with £SRO and severe peripheral vascular d1seu1;,
was hospitalized for a left femoral-popliteal
bypass and lumbar sympathectomy approximately 2
months after administration of a third injection
of recombinant hepatitis B . vaccine lot
g74/C-K446. His hosp1 ta l course was coq> 11 cated
by postoperative blood loss, hypotens1on and
hyperkalem1a. He subsequently experienced a
respiratory arrest requ1r1ng resuscitative
measures. Post resuscitation, the patient was
comatose and decerebrate. His condition further
deteriorated and he died {b) (6) days after admission
to the hospital.
25391/4
1/21/86
Tab1e 1
Antibody Responses Among lniti•11y Seronegative Jt>nrespondel"S to P1agna-Oerilled Hepatitis B Vaccine

(Dialysis Patients) Fo11011ing Vaccination with 20 or 40 111eg Doses of Yeast Recaminant
Hepat\tis 8 vaccine Lot 914/C-K446 at 0, l, and 6 flonths in Study 816
0 n:a 40mca
GftT lnlIU/1111 GnT C111IU/ial )
Tilll!
(Months)
7, '1litll Anti-Has
5/N > 2.1 11tIU/ia1 ~ 10
All
Vaccinees S/N ~
-
- rs
2. 1 111IU/llll ~
\ with Anti-tlls A11 -
10 S/N~2.1 inIU/111 ~ 10 Vaccinees S/N~2.1 IIIU/1111
rs
~ 10
1 0(0/4) 0(0/4) 0.3 -- --- 0(0/3) 0(0/3) 0.3 --- ---

3 25(1/4) 25(1/4) 1.1 53.0 53.0 25(1/4) 25(1/4) 0.8 16 .1 16.1
6 0(0/Z) 0(0/2) 0.3 -- --- 33(1/3) 0(0/3) 0.9 9.5 ---

7/8 100(1/1) 100(1/1) 136.9 136.9 136.9 33(1/3) 33(1/3) 2.1 49.4 49.4
12 50(1/2) 50(1/2) 3.4 38.5 38.5 61(2/3) 33(1/3) 3.0 9.3 22.3
25391-S/cfs 0
12/16/85 0
09
-D
~
Table 2
PATIENT COUfT CLINICl l t0t1Pll INfS
REtot1BIHINT HEPlTl~IS B VACCINE
STUDT 0816
1REITl1EHT
LOT H\Jl18ER CK't46
DOSE 20 '1CG
Pl lIEHT CLASS: NONIIESPONUERS co ,
I TOTAL VICCI N!:ES f 5 PATIENTS, - DOSE 1 f

1----------------------------------------------------------------------------
I DAYS POST VACCINATION •• NUHeER
CLINICAL
C0nPLI INTS
1----------------------------------------------------------------------------•
I O I 1 I 2 I 3 • 4 I 5 I
WITH
ltotfPLAIITTS
.................................... ,.......... l••······•• l••······•• l••······•• I••······-···········•····· ···-···········
-------------------------------- ·--•----------l----------t----------l----------
PERS<Jm Milli Cotff'lllHTS I O I O I O I O
l----------1----------
• 0 I O
1----------1I -----------
I 0
I c o.oz , • c o.oz, I c 1.ozt I c o.ozt • c o.ozt I c o.ozt • I c o.oz1
-----------------------------------1----------•----------l----------l----------l----------1
PERSom 111TH NO COt'IPllINTS I 3 • 3 • 3 • 3 I 3 I
----------I----------
3 I
I-----------
I 3
I uoo.oz, I uoo.oz , I n oo.o;o I noo.o:o I noo .oz, • u oo .ozt I • n oo.oz,
-----------------------------------•----------
Pt:RSONS 111TH NO Di l l I 2
t----------1----------1----------1
I 2 I 2 • 2 I
----------
2
I----------I----------
I 2 I
I-----------
I 2
I ( 40 . 0Z t I ( 40.07.1 I ( 40.0Zt I ( 40.0Zt I I ~0.07. t I ( 40 .0Zt • • f 40. 0ZI
0
0
QI
-0
~
Table 2 (oont.)
PATIENT CO\MT CLI NICAL COt1PLAINT9
RECOffl!lNANT HEPATil'.lS 8 VACCIHE
STUDY : 0816
lREATnENT
lOT NU 18(11 : Clt4ft6
DOSE : 20 t1CG
PATIENT CLASS: NOURESPONUERS 10 )
-- --------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I S PATIENTS) - DOSE 2 I
1-
I ·--------------------------------------------------------------------------1
DAYS POST VACCINATION I tM!BtR
1---------------------------------------------------------------------------I
CLINICAL
COMPLAINTS
................................... I
, O
.......... I
, 1
..........,• 2
,
..........
-----------------------------------1----------I----------I----------
• 3 • 4 • 5
..........•..........•..........
I----------I----------
,I
MITH
•cOtlPLAINTS
..........•..........
I----------I----------I-----------
PERSONS MITif COMPLAINTS I O I O • 0 • D I O • O I • O
• c o.oz, • c o.07.l • c o.o:o I I o.o:o I , o.or., I , o.o;,o I I c o.oz1
-----------------------------------1
,ERSONS NITH NO COMPLAINTS I----------l----------•----------l----------l----------•----------l----------l-----------
4 I 4 I 4 I 4 I 4 I 4 I I 4
I cioo.ox, I c100.ox1 I c100.ox1 I 1100.07.1 I 1100.07.1 I 1100.07.1 I I 1100.or.1
-----------------------------------1
, ERSONS NITH NO DATA I ----------
1 l----------l----------l----------l----------l----------l----------l-----------
I 1 • l I 1 I l • l I I l
I c 20.07.I I c t0.07.1 I c 20.07.J • I 20.07.I I c 20.07.J I I 20.07.1 I I I 20.07.I
0
0
-0
0
0
Table 2 (cont.)
PATI!NT COUNT CLINICALCottPLAIKTS
R£COl18IHAKT HEPATI ! IS 8 VACCIIIE
Sl\JDY 0516
TRE ATtttHT
LOT NUt18ER CK'+'46
DOSE I eo MCG
PATIENT ClAss: HONRESf'ONOERS ( 01
I TOTALVACCIH£ES I J PATIEHTSI - DOS£ J I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I Nl.118ER
CLINICAL
CCl1PLAINTS l----------------------------------------------------------------------------1
I O I 1 I Z I J I - I 5 I WITH
IC011PLAINTS
·································••l••······••l••·······•l••······•· l••···········..··••Hl••······••l••······••I••········
-----------------------------------1----------l----------t----------l----------l----------1----------l----------l-----------
l'ERSONS WJ TH Cot1PUIHTS I O I O I O I o I o I o I I o
I I 0.07.1 I f o.o;o I f 0.01.I I I 0.01.1 I I 0.07.I I I 0 . 01.1 I I I 0 . 01.1
-----------------------------------l----------l----------1----------1----------1----------I----------I----------I-----------
PERSONS WITH tlO COffl'LAINTS I 3 I 3 I 3 I 3 I 3 I 3 I I 3
I u oo.o:o I 1100.01.1 I (100.0)0 I 1100.01.1 I 1100.01., I 1100.01.1 I I UOO,Cl:1.1
--------·--------------------------1----------1----------I----------I----------I----------I----------I----------I-----------
PERs~ Wtllf NO D ATA I o I a I a I o I o I e I I e
I I 0 . 0:1.J I I 0.01.1 I I 0.0:1.1 I I 0.01.1 I I 0.0:1.J I I 0.0:1.1 I I C 0.01.1
0
0
-0
-
0
Table 3
PATIENT COUNT "AXI,_,,., TEHPERAT\JRES
RECOMeJHANT HEPATIT}S B VACCJH!
STUOT 0816
Tif£ATHUIT
LOT NUMBER 0:446
DOSE ZO t1CG
PATIENT CUSS NOllRESPOM>ERS (DJ
• TOTAl VACCIH£ES I 5 PATJEHTSJ - DOSE 1 I

1--------------------------------·
I ------------------------------------------------------1
DAYS POST VlCCIHlTION I NUl'fflER
•---------------------------------------------------------------------------------------1
NAX TEttPERAT\JRE
CDEG F • OR Al J •
•
0 I l
•
I t
•
• J
•
• 4 I 5 I I
, ,
WITH
I NA>< TEtfP
.......................................................................................... .......... ..........•..........
• I I I
"°""Al • l I l I l I l I l I l I I l
• C ]].37.) I C 50.07.) • I ]].3)0 • C 33.3l0 II 50.0lO II 50.0:I!) I I ( 33.3%)
I I • • I I I I
< ~9 • z I 1 I t I z I 1 I 1 I I z
• I 66.7l0 I I 50.0lO I C 66,77.) I I 66.77.) I C 50.0%) I ( 50.0Y.I I I I 66.7)0
------------------------•----------•----------l----------•----------l----------l----------•---------------------I-----------
TENP£RATIJRE TAKEN • 1 I z • 1 I 1 I r I r I I 3
• I 60.0X) • ( 40.0Y.J • I 60.0?.I • I 60.0lO • I 4'0.0lO I I ltO.OlO I • I 60.0lO
---------------- .-------l----------l----------•----------•----------l----------1----------1---------------------I-----------
TEHPERATIJRE HOT TAktN J Z I 3 • £ • Z • 3 I 3 I I Z
• r 1to.o,:, I, 60.oi, I, 1to.ox1 I, Ito.ox, I , 60.ox, I , 60.ax1 I I c 1to.ox1
:>
C
.0
0
N
Table 3 (cont. )
PATI ENT COUNT "AXINUn TEffl'ERATIJRES
RECOt18INAHT HEPATIJIS 8 VACCINE
STIJDY 0916
TREATI1EHT
LOT HUMBER Ck446
DOSE 20 MCG
PATIENT ClASS: HOHRESPOHDERS ( D )
I TOTAL YACCINEES f 5 PATIENTS ) - DOSE 2 I

1---------------------------------------------------------------------------------------
I DAYS POST VACCINATION II tl\JlfflER
NAX TENPERATIJRE
(DEG F,ORAL I
l---------------------•-----------------------------------------------------------------1
I O I l I ! I 3 I 4 I 5 I I WITM
I NAXTENP
--•••••••••••••••••••••l••••••••••l••••••••••
I I
l••••••-••l••••••-••l••••••••••
I I I
l••••••"••l••••••••••l••n••••••I••••••••••
I I I
N!lltt1AL I t I z I z I z I z I z I I :z
I • s o . 01.1 I r 66.r.1.1 I• H.r.1.1 I f 66.T/. I Ir 66.r.t. , I• 66.T/.I I I , s o .o;o
I I I I I I I I
< 99 I 2 I 1 I 1 I 1 I 1 I 1 I I z
I t so.o:o I I n.1:0 I I 33.3?.I I I 33.JY.I I I 33 .3?.I I c :n.3;0 I I c so.o;o
------------------------l----------l----------l----------l----------l----------1----------1
TENPERATIJRE TAKEN I 4 I 3 I 3 I 3 I 3 I 3 I
---------------------I-----------
I 4
I I 80.0?.) I I 60.01.1 I I 6 0.0lO I I 60.0Y. I I I 60. 0Y. I I ( 60.0lO I I I 80.0Y.I
------------------------1
n:ttPERATURt HOT TAKEN I
----------1----------l----------l----------l----------l----------l---------------------1-·---------
l I t I I! f t I Z I I! f I 1
I I to.oio I f 40.01., I c 4 0 . 0Y.I I I 40.01.1 I r 40 .01.1 I c 4 0.01.1 I I , u.o:o
0
0
-0
0
\JOI
Table 3 (cont.)
PATIEffT COUHT HAXIHUt1 TEHPERAT\JRES
REC0118INANT HEPATI1I5 9 VACCIHE
STUDY De16
TRt:ATt1£NT
LOT HUMBt:R CKqq6
DOSt: 2:D 1'1CG
PATIENT ClASS NONRUPONOERS lO l
I TUTAL VACCINEES I J PATIENTSI - DOSE J •

•---------------------------------------------------------------------------------------•
I DAYS POST VACCINATION I NUt1MR
HAX TEMPERATURE
(DEG F', CRALi
l---------------------------------------------------------------------------------------1
I O • 1 I t I 3 • 4 I 5 I I
MITH
I "AX TEMP
••••••••••••••••••••••••••-••••••••-••••••l••••••
I I- I
..••••••••••••••••
I I
..••••••l•'""'••••••l••••••••••
I I
I•••••••••••••••••••••
I
NORNAl I Z I t I Z I Z I Z I t I I t
• c100.01.1 I l l OO.OY.I I 1100.01.1 I 1100.07.1 I 1100.01.1 I 1100.01.1 • I 1100.ox t
------------------------l----------l----------l----------l----------l----------1----------1
taff'ERATURE TAKEN I Z I l I 2 I I! I t I t I
--------------------- Il-----------
I!
I I 66.7Y.I I I 66 ; 7Y.I I I 66 . T/.J I I 66.7Y.l I I 66.77.l I I 66.77.1 I I I 66.7Y.I
------------------------l----------1
TEt1PERA~ E HOT -TAKEN I 1 I
----------l----------
1 I 1
l----------l----------l----------l---------------------1
I 1 I l I 1 I I
-----------
1
I I 3].37.1 I ( Jl.37.) I ( 3 3 . 37. I I I 33.JY.I I I 33 .31.1 I I 33.3)0 I • I 33.l:f.l
0
0
-0
0
&;:
Table 4
PATIENT COUNT CLINICAL COHPLAINT9
RECOHBINANt HEPATITIS B VACCINE
STUOY 0816
TRUTt1ENT
LOT NUt18ER CK4't6
DOSE ftO t1CG
PATIENT CLASS NOflRESPOtCJERS (0 t
I TOTAL VACCIHEES r 4 PATIENTS, - DOSE l I

ll----------------------------------------------------------------------------
DAYS POST VACCINATIOH
1I t-U1BER
l----------------------------------------------------------------------------1
CLINICAL
COffl'LAINTS
..................................., I o • 1
, I 2 • J
, I 4 , I 5 , I WITH
l cOMPLAINTS
..........•.......... ..........•.......... .......... .......... ..........•..........
-----------------------------------•---------- •----------1----------l----------1----------1----------1---------- I-----------
PERSONS WITH CONPU INTS • 0 I O • 0 I O I O I O I I 0
I ( O.OY.I • C o.o;o I ' O.OY.I I ( o.o;o • ( o.oY., I I o.oY., I I I O.OY. I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------
PERSOHS MITH HO Cot1PI.AltmS • 4 I 4 • 4 • 4 • 4 I 4 I
I-----------
I 4
I uoo.oY.1 I uoo.o;o I uoo.ox, • noo.ox, I uoo.ox, I 1100.ox 1 I • u oo.ox,
-------- ·--------------------------1I ----------l----------l----------
PERSONS MI TH HO DATA O • 0 I O
l----------•----------
• 0 I O
l----------
• 0
l---------- I•-----------
• 0
• ( O. 07. J • I O. 07. , I ( 0. 07. , I f O. o;o I I O. o;o I ( 0. 07. , • I I O. OY. I
0
0
~
0
JI
Table 4 (cont.)
RECOM91HANT HEPATI~IS B VACCINE
ST\JUT 0816
TRUTI1EHT I
LOT NUf18ER CK446
DOSE 40 ttCG
PATIENT CLASSI HOHRESPOHDER!I IDI
I TOTAL VACCIHEES C ~ PATIENTS! - 005£ 2 I

1----------------------------------------------------------------------------I
l----------------------------------------------------------------------------1
CLINICAL
COt1PLAINTS
,
I O f
, 1 f
, 2 I
, 3 I
,
4 f
,
5 f
, , WITH
ICOHPLAINTS
................................... •......... .......... .......... .......... .......... .••....... .......... ..........
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH COl'tPLAtNTS I 0 I 0 I 0 I O I 0 f 0 I I 0
I c o. o:r., I c •. o;o I I o • o:r.1 I c o. or. 1 I I o. ox I f I o. o,n I I c o. o:r. ,
-----------------------------------1----------l----------l----------l----------l----------l----------1----------I-----------
PERSOtlS WITII tlO CONPLAINTS I 4 I 4 I 4 I 4 I 4 I 4 I I 4
I (100.07.) I fl00.07.I I r100.o:r.1 I 1100.07.1 I r100.o:r.1 I (100.07.1 I I 1100.0Y.I
-----------------------------------1-------
PERSOMS WITH HO DATA I
---l----------l----------l----------1----------1----------1----------I-----------
O I O I 0 1 0 I O I O I 1 0
I ( 0.07.l I ( 0.01.1 I I 0.07.) I ( 0.07.1 I ( o.o;o I t o.o:o I I I D.07.)
0
0
4
0
O"
Table 4 (cont. )
PATIENT C~ ClI HICAl CONPlAIHTS
RECOt1BINAHT HEPATITI S B VACCINE
SlUIJY 0816
TREATttENT
lOT HUt18ER CK446
DOSE 40 t1CG
PATI ENT CLASS HOHRESPOMJERS 10 )
----------------------------------------------------------------------------------------------------------------------------
I TI>TAL VACCINEES ( 3 PATIENTS) - DOSE J I
1f ----------------------------------------------------------------------------
II tMtBER
CLI NICAL
Cllffl'lAINTS
1----------------------------------------------------------------------------I
I O I 1 I 2 I J I 4 I 5 I NITH
lt011PLAIHTS
•••••••••••••••••••••••••••••••-••t••••••••••t••••••••••l•••••••••••"••••••••l••••••••••l•••••••••• I•••••••••••••••••••••
-----------------------------------1• ----------l----------•----------
PERSOHS NITII Cot1PLAIMTS I I O I 0 II----------I----------I----------
0 I 0 I o I
I----------I-----------
I o
I < o.o;o I c o.o?., I c o.o?.J I • o.o?., • c o.oz, I ( o.o?. J I I c o.ox ,
-----------------------------------•----------
PERSOHS NITM NO COt1PLAINTS I J
l----------l----------1
I J I 3 I
----------1----------1----------I----------I-----------
J I S I J f I J
I 1100.oz, I uoo.oz, I uoo.oz, I noo.o:o I 1100.0?.J I noo.ox, I I uoo .01. ,
-----------------------------------1
PERSONS WITH HO DATA I
----------1----------1
O I O I
----------1----------1
O I O I
----------1
O •
----------1----------1-----------
0 I I 0
f I 0. 0?.) I C 0. o;o • C O. 07.1 I C O. 07.) • I O. 07. J I ( I . 0?. ) I I l O. 01. J
0
0
.0
0
---4
Table 5
PATIENT tOIJHT " AXIHl.l1 TE"PER AT\IRES
RECOH8lNAMT HEPATI~I S B VACCINE
STUDY 0816
TREATMENT
LOT NIJl18ER CK446
DOSE 40 HCG
PATIENT Cl.A!l!I NONRESPONDER!I ID)
I TOTAL VACCI NE£!! I 4 PATIENTS) - DOSE l •

1I ---------------------------------------------------------------------------------------I
OAY!I POST VACCINATION I t1Ut18 £R
NAX TEHPERA~E
I DE(; F, OHLI
•---------------------------------------------------------------------------------------1
I O I l I Z I l I 4 I 5 I I • HAMITff
X TEHP
••••••••••••••••••••••••l••••••••••l••••••• ..• •••••••••••••••••••••• l••••••••••l•••••••••• l••••••••••I•••••••••••••••••••••
I I I I I I I I
NOOrtAL I 1 I l I 1 I 1 I 1 I 1 I I l
I 1 2s , or., I 1 2s.or.1 I, 2s.01.1 I c 2s.01. 1 I , zs.ox1 I , 25.01.1 I • , 25,011
I I I I I I I I
< 99 I l I z I 1 I 3 I z I l I I 1
I I 75.0:0 I I 50.01.I I I 25.0Y.) • I 75 . 0X J I I 50.01.1 I I 75.01.) I I I 25 .01.1
I I I I I • I I
99 - 99.9 I o I 1 I z • o I 1 I o I • 2
I I O. or. l I I ZS, 01.) I I 50, or.) I I O, OY. I I I 25, ox I I I O. ox ) I I I 50. ox I
------------------------1----------•----------1----------1
TErtPERATURE TllltEH I . 4 I 4 I 4 I----------1----------•----------1---------------------•-----------
4 • 4 l 4 I I 4
• 1100. 0Y.) I 1100.0X) I 1100.0Y.) I 1100.0)0 I 1100,0XI • 1100.0XI I • 1100 . 01.1
------------------------ l----------l---------- l----------l---------- l---------- l----------1---------------------1-----------
TEHPER ATURI! NOT TAKEN • 0 • 0 • 0 I O I O I O I I 0
I I O, 01. J I I O. or. I I 1 0. o;o I I O, 01. J I I O. 01. J I I O. DiO I I I O. 01. I
0
0
.lJ
0
a,
Table 5 (cont. )
PATIENT COUNT ffAXI..._.., TEffl'ERATURES
RECD'18IHANT HEPATilIS 8 VACCINE
STUDY 0816
TlfEATMEHT
LOT NUMBER CK446
DOSE 40 t1CG
PATIENT CUSS t«»llESPONDERS fDJ
• TOTAL VAttIHEES f 4 PATIENTS) - DOSE Z I

1---------------------------------------------------------------------------------------I
• DAYS POST VACCINATION I NUmER
nAX TEffl'ERATURE
fDEGF,ORALJ
•--------------------------------------------------------------------------------------1
• 0 I 1 It • 3 • 4 • 5 • I
WITH
IHA><TEttP
o•o••••••••••o••••••••••••••o•••••••••••••••••••a..•••••••••••••••l••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
HORrtU •• 1 •• l •• 1 II l •I 1 •• l II •I 1
I , zs.o;o I , zs.oz1 I , zs.o;o I I zs.o;o I , zs.oz1 • , zs.o;o I I I u.o;o
I I I I I I I I
< •• • z I t -I z I z I t I 2 I I I
I 1 50.07.1 I c so.or.I I f 50.07.I I I so.o?.I I I 50.07.1 I I so.oz, I I I zs.oY.J
I I • I I I I I
99 - c,9,9 I 1 I 1 I 1 • l I 1 I 1 I I z
I ( 25.0)0 I ( 25.0Y.I I ( ts.0-,:1 • I ts.o:.n I I t!S.07.1 I I zs.oi, I I I 50.0-,0
------------------------1----------1----------l----------•----------l----------l----------•---------------------•-----------
TEHPERATURE TAKEN • 4 I 4 I 4 I 4' • 4 • 4 I • 4
I noo.01.1 I noo.o;r.1 I noo.ox, I noo.or.1 I noo.ox1 I uoo.o,o • I noo.or.1
------------------------l----------l----------•----------l----------l----------l----------1---------------------1-----------
TEHPERATURt NOT TA~EN I O I O I O I O I O I O I I 0
I , 0.01.1 I , a.ox, I c 0.07.J I c o.or., I , o.or., • , o.o;o I I , o.or.1
0
0
.0
0
.0
Table 5 (cont.)
PATIENT COUNT nAXI~ TEnP£RATUlES
RECOt18INANT HEPATI~IS B VACCINE
ST\IDY I 0816
TR l:AfflEHT
LOT HUMBER I CK4%
DOSE I ltO nee
PATU HT CLASS: NOtllUSPOMJERS CDI
----------------------------------------------------------------------------------------------------------------------------
I TOTAL VACCINEES I J PATIENTS) - DOSE J •
l---------------------------------------------------------------------------------------1
HAX TEHPERATUIIE •-------------------------- - ---- --------------------------------------------------------1 WITH
IDE6 F, ORALI • 0 I l I 2 • 3 • 4 • 5 • • I HAX TEHP
a•••••••••••••••••••••••••••••••..•l•~•••••••••••••••••••••••••••••• l•••••••••• I••••••••••••••••••••••••••••••-•••••••••••
I I • I I I I •
< 99 I 2 I 2 I 2 • J • J • J • I 2
I 1 66 . na 1 1 66.71.t I • 66.T/.J I uoo.oY. 1 • 1100.oY.1 • uoo.o;o I 11 66.n J
• I I • • I I I
99 - 99 . 9 • l I l I l • o • o .I o I I l
I I U.37. J I ( 33 . 37. t I I U.JY.I I I o .o:o • I 0 .Ol!I I I O.0Y.J I I I 33 .liO
------------------------1----------1----------
TEHPERATURE TAKEN • 3 I J
•----------
• 3
l----------l----------•----------•---------------------
• 3 • 3 • 3 •
•-----------
• 3
I 1100.01., I n oo.oio I 1100 .0:r.1 I 1100.0;0 I uoo.o;o I 1100.oY. J I I noo.oio
------------------------•----------1----------•----------•----------1----------1
TEffllERATURE MOT TAKEN I O I O I O • 0 • 0 I ----------1---------------------1-----------
O I I 0
• , o .o;o I c 0 .01. 1 I c o .ox J I , o .or., I c o.oY. 1 • ,. o .o:r. , I I I o.o:r. t
0
0
-
-0
0
00911

doses of yeast recombinant vaccine among:
1. healthy adults immunized previously with
plasma-derived vaccine who were nonresponders
(anti-HBs negative)
2. preinmune healthy adults
VACCINE: Hepatitis B Vaccine (Recombinant) - Alum Adsorbed:

Lot #972/C-K444 (10 mcg/ml)
PRIMARY Robert P. Bishop, M.D.

INVESTIGATOR: Director, Health Services
Merck &Co., Inc.
SECONDARY Edgardo P. Avancena, M.D.

INVESTIGATOR(S): Joseph C. Rogers, M.D.
Joseph P. Ro111ano, M.O.
Merck & Co., Inc.
West Point, PA & Rahway, NJ
STUDY LOCATION: Merck & Co., Inc.

Merck & Co., Inc.
Rahway, NJ 07065
2471 I/1
1/19/86
00912
Study 817
STUDY POPULATION: The study population will cons1st of 40-50 healthy

adults of either sex (excluding pregnant females), who
are employees of Merck & Co., Inc. Half of the
population will consist of persons wUh pre-existing
hepatitis B antibody which may be either naturally
acquired or plasma vaccine induced. The other half
will consist of persons who have been vaccinated with
plasma vaccine but failed to develop detectable
antibody to hepatitis B. All participants must be
negative for anti-HBc and HBsAg, and have a non11al ALT
leve 1.
PROCEDURE: Study participants are allocated to one of two
regimens as shown below. All injections are
intramuscular.
Time of
Group Dose Vaccination
1. Prei1m1une 5 1.0 ml (10 mcg) 0
2. Nonresponders 4 1.0 ml (10 IIICg) 0, 1 & 6 mos.

for five days after each injection and also to record
any local or systemic complaints they may have during
this period.
participant approximately 2 weeks before the first
vaccination. Post-vaccination blood sa111>les are
obtained at l, 2, 3, 6, 8, 12 and 24 months. The
samples are assayed for HBsAg, anti-HBc, anti-HBs,
yeast antibody and ALT. Those with antf-HBs titers
> 25 mIU/ml may be tested for the proportions of
anti-! and anti-g activity.
24711-2
1 /19/86
00913
Study 817
RESULTS: NONRESPONOERS TO PLAS~ VACCINE:

10 mcg Lot '972/C-K444 at 0, 1, and 6 months
Injection No .
.J_ _2_ _3_
4 4 3
Sero logic data are avi lab le for two study
participants at 7/8 months.
At seven months neither of the two vaccinees
tested had seroconverted. Table l shows
seroconversion rates and GMT's for up to 7/8
months of follow-up.
3. Clinical Co~pla1nts:
Clinical follow-up data are available for four
participants fol lowing the first two injections
and for three after the th1 rd injection.
reported during · the five days of follow-up
following each injection are provided in Table
2.
Frequency · in \ by Injection No.

Type of CC.,laint _L_ _2_ ..J_
Inj«~ion Site 25(1/4) 0 (0/4) 0 (0/3)
Systemic 25(1/4) 0 (0/4) 0 (0/3)
There were no serious or alarming adverse reactions

2471 I/4
1 /19/86
Table l
ANTIBODY l!ESPOHSES FOLLOWING VACCINATIOtl MITH RECOtlBIHAHT HEPATITIS 8 VACCIME
STUDY 0817
POPULATION NOURESPOHOEl!S IHI
DOSE 10 t1CG
LOT CK444
l!EGittEN 0, 1, AHO 6 ttOHTHS
I Y. WITH AHTI•HBS I GMT ltfIU/l'ILI I

l---------------------------------------1-----------------------------------------------------I
I I I RESPONDERS I
TittE
lt10HTHSI
1---------------------------------------l-----------------1-----------------------------------I
I SIN>= 2.1 I MIU/Ml>= 10 I All VACCINEES I S/N >= 2.1 I MIU/NL>= 10 I
···········-·········· ..···········································•*••···········································
PRE VAC 0Y. 10/41 I 0Y. 10/4) 0.4
I
1 MONTH O?. (0/31 I OY. C0/31 o. 3
I
2 MOlffHS 0:t. (0/1) I 01. 10/1) 0. 3
I
3 110HTHS 01. 10/2) I 01. (0/21 0. 3
I
6 l'IONTHS O?. 10/11 I ox (0/1 I 1. 9
I
7/8 MONTHS 01. 10/2) I 01. (0/21 0.7
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
0
0
-
-.0
-
. i:,
Table 2
PATIENT COUNT CLIHICAL COl1PLAIHTS
RECOHBIHAHT HEPATITIS B VACCINE
STOOY 0817
TRUTHEHT
LOT N\11!8£1! CK444
DOSE 10 MCG
PATIENT CLASS NOIIIIESPONDIERS IHI
I TOTAL VACCitlEES l ,_ PATIENTS I - DOSE 1 I

l----------------------------------------------------------------------------1
• DAYS POST VACCINATION • t1Ut181:R
CLI NICAL
COMPL AINTS
•----------------------------------------------------------------------------1
• 0 • l • 2 • 3 I 4 I 5 I WITH
ICDHPlAIHTS
•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••I••••••••••
I I • I I I I I
REACTION, lOC U UNJIECT . SITE I I l I 0 I I I 0 I 0 I 0 • • l
I l 25.0XI • l 0.07.1 I l 0.IXI I l 0.0XI • l 0.0XI • l 0 .0?.I • I ! 25 . 0XI
-----------------------------------
SORENESS
•----------•----------•----------•----------•----------1----------1----------1-----------
• l • 0 I I • 0 I O I O I I l
I , 25. 01.1 I I o. 01.1 I I o. ox I I l o. 01.1 I l o. ox, I I o. o;: , I I 1 25.01.1
-----------------------------------1----------I----------
SYSTEHIC I O I O
I----------I----------I----------
I l I O I O
I----------I-
I O I ---------1-----------
I l
I I O.OXI I I 0,0;:1 • ! 25.07.I I I 0.07.1 • ! O.OXI I I O.OX> I I ! 25.07.1
--------------------------------------------------------
1 • • I I
t1USCULOSKELETAL • O • 0 • l I O I O • 0 I • 1
o.ox> Il I t a.ox, I r a.ax, • t o.ar.1 I
o.ox, • 1 zs.ox, • 1 25.or.,
I I • I I I I
SHOULDER PAIN I o I o I l • o I O I O I I I
I I a.o;o • ( 0.0;:1 I I 25.07.) I I 0 . 0½1 I I 0 . 07.) I I O.DX) I I I 25.0XI
-----------------------------------1
PERSDNS WITH COMPLAINTS I----------l----------•----------•----------•----------l----------•----------I-----------
l I O I 1 • 0 I O I O I • 2
I 1 2s.ox1 I I a.ox, I 1 2s .ox, • 1 o.ox1 I I o.ax, • 1 o.ox1 I I I so.ox1
-----------------------------------•----------l----------1----------I----------I----------I----------I----------I-----------
PERsor1s WITH HO cor1P U INTS I 3 I 4 I 1 I 4 I 4 I 4 I I z
I I 75.07.1 I 1100.0i:l I I 75.DXI I 1100.0XI I 1100.0XI I 1100.0XJ I I I 50.0%1
-----------------------------------1----------1----------I----------I----------I----------I----------I----------I-----------
PERSOHS WITH HO ouA I a I o I o I o I o I o I I o
I I O.OXl I I O.OXl I I O.OXI I I O.OXI I t 0.07.1 I I 0.07.1 I I I O.OXI
0
0
-
,0
-
1.11
Table 2 (cont.)
RECOt1BIHAHT HEPATITIS 8 VACCINE
STUDY 0817
TREATt1ENT
LOT IMl8ER CK444
OOSE 10 t1CG
PATIENT CUSS NOtlRESPONDERS IH)

l----------------------------------------------------------------------------1
I DAYS POST VACCIHATIOH I HU11BtR
CLINJCl l 1-----------------------------------------·---------------- ------------------I WITH
COMPLAINTS I O I l I 2 I 3 I 4 I 5 I IC011Pll IHTS
•••••••••••••••••••••••••••••••••••l•••••••••• l••••••••••l••••••••••l•••••••••• l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSoHs WITH COl1PUIHTS I O I O I O I O I O I O I I 0
I I 0, O?. I I I O. 0% I I I O. 0lO I I 0. O?. I I I O. O?. I I I O. O?. I I I I 0. OX I
------- --- -- ------------------- - ---1---- ------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH NO tOMPLl IHTS I 4 I 4 I 4 I 4 I 4 I 4 I I 4
I 1100.or.1 I 1100.or.1 I 1100.or.1 I 1100.or.1 I 1100.or.1 ~ 1100 . or.1 I I 1100.01.1
-----------------------------------1----------l----------t----------l----------l----------l----------l----------l------·----
PERSONS WITH NO OI TA I O I O I O I O I O I O I I 0
I l O.OY.I I I O.OY.I I I O. OY.I I I O.OY.I I I O.OY.I I I O.OXI I I C 0.01/.l
0 ,
O '
-0 .
....a- '
-
Table 2 (cont . )
RECDHIIIHANT HEPATITIS 8 VACCI NE
STUOY 0817
TREATH£NT
LOT HUMBER l CK,,~
DOS[ 10 t1CG
PATJ£HT CLASS: HOtlRESPON>f RS IH I
• TOTAL YACCINEES I 3 PATIENTSI - DOSE 3 I

1I ----------------------------------------------------------------------------I
DAYS POST VACCitlATION I NUt18ER
•----------------------------------------------------------------------------1
CLINICAL
COt1PLAINTS I O I
,1 • 2 I 3 I
, 4 I S I
, WITH
ICOttPLAIHTS
...................................•.......... ..........•.......... ..........•...•...... .......... .......... ..........
-----------------------------------•---------- l----------•----------l----------•----------1----------1---- -----1I -----------
, ,
PERSotlS WITH CCt1PlAINTS • 0 I O I O I O • O • O I o
• I O. o;o I I O. 0% I • I O. ox I I I O. ox I • I O. O?. I I I O. G?. I I I I O. ext
-----------------------------------1----------l----------l----------l----------•----------I----------I----------I-----------
PERSOHs WITH NO CotfPLAIHTS I 2 I 2 I 2 I 2 I 2 I ! ' I I !
I (100.0?. I I ( 100.0?.t I 1100.0%1 I (100.0XI I 1100. 0Z t I ( 100 . 0Z I I I 1100 . 0Z I
-----------------------------------•----------l----------l----------
PERSOtfS WITH HO DATA I o I o I o I
l----------l----------1----------1
o I O I O I
----------1I -----------
o
I I o.oio I I o.o;o I 1 0.01.1 I I o.o:o I 1 0.01.1 I c o. o:o I I I o.o;o
-·
0
-0
....., .
·-
Table 3
PATIENT COUNT HAXI111Jtt TEHPERATURES
STUDY 0817
TRE ATHENT
LOT IU15ER I Cl<444
DOSE 10 t1CG
PATU HT CLASS : HOIIRESPOMI ERS (H I
I TOTAL VACCIHEES t 4 PATIENTS) - DOSE 1 I

1---------------------------------------------------------------------------------------I
HAX TEMPER ATURE
lOE6 f , GR ALi
l---------------------------------------------------------------------------------------1
I O I 1 I 2 I 3 I 4 I 5 • •
WITH
• HAX lEHP
••••••••••••••••••••••••l•••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••I•••••••••••••••••••••
I I I I I I I •
< 99 I 4 I 4 I 4 I 4 I 4 • 4 I I 4
I 1100.01.) f (100.01.1 f (100.07.I I 1100.0Y.l I 1100.07.1 I 1100.07.) I I 1100 . 0ZI
------------------------l----------l----------l----------l----------l----------t----------1---------------------1-----------
TEMPERATURE TAl<EH I 4 I 4 I 4 I 4 I 4 I 4 I I 4
I 1100.07.l I 1100.01.1 I 1100.07.1 I 1100.0ZI I t l 00.07.1 I 1100.07.l I I 1100 . 01.1
------------------------1----------1--------·
TE11PERATURE HOT TAKEN I O I O •
-l----------l----------•----------1----------I---------------------I-----------
0 I O I O • O I I 0
I t o.o:o I I o.o;o • c 0.01.1 I 1 0.01.1 • 1 o.oz, I , o.o;o I I , o.o;o
0
O ·
-·
..0
--
OD
Table 3 {cont.)
PATltNT COUHT t1AXll't.Jt1 Ttt1PERAT\JRES
RECOl181NANT HEPATITIS B VACCIIIE
STUDY 0817
TREATMENT
LOT HU181:R CK444
DOS! 10 11CG
PATIEHT CLASS HOHRESPONIERS lHI
• TOTAL VACCINEES C 4 PATIEHTSI - DOSE 2 I

1---------------------------------------------------------------------------------------I
I DAYS POST VACCIHATIOH I NUffflER
HAX Ttt1PERATUR£
l0t6 F, ORAL)
1---------------------------------------------------------------------------------------I
I O I 1 I 2 I 3 I 4 I S I I I ttAXWITH
UHP
••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••o••••••
• I I I I I I I
HOl!t1AL I 1 I 1 I 1 I l I l I 1 I I 1
I l 25.0XI I l 25.0XI I l 25.0XI I l 25.0XI I l 25.0XI I l 25.0XI I I l 25.0XI
I I I I I I I I
< 99 I. J I J I J I J I l I J I I 3
I 1 1s.ox1 I , 1s.ox1 I 1 1s.ox1 I 1 1s.ox1 I c 1s.o:o I r 1s.ox1 I I 1 75.o;o
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TE11PEAATURE TAKEN I 4 I 4 I 4 I 4 I 4 I 4 I I 4
I noo.o,o I 1100.07.1 I 1100.07.1 I (100.0)0 I (100.0XI I (100.0~I I I (100.0XI
------------------------l----------l----------t----------l----------l----------l----------l---------------------l-----------
TE11PERATURE NOT TAKEN I O I O I O I O I O f O f I 0
I I o.ox1 I I o.o;o I I o.ox1 I I o.ox• I , o.o;o I I o.ox1 I I c o.ox,
0
0
...
,D
- ,D
Table 3 (cont.)
PATJEHT COUNT HAXltf.WI TE11PERATURES
RECONBIHAHT HEPATITIS B VACCINE
STUDY 01'17
TRU THEHT
LOT NU1BER CK444
DOS£ 1 0 t1C6
PATIENT CLASS HONRESPOtl>ERS (HJ
I TOTAL VACCIHEES C l PATIEHTSI - DOSE 3 I

1I ---------------------------------------------------------------------------------------
DAYS POST VACCINATIOH II tut1BER
NAXTEHPERATURE l---------------------------------------------------------------------------------------1 MITH
CDEGF,ORALI • 0 • 1 • ! I l I 4 • 5 I • I NAXTEMP
••••••••••••••••••••••••••••••••••••••n•••••••••••••••••••••••••••••••••••••••••••••••••• •••••••••••••••••••••••••••••••••
• I • • I I I I
< 99 • z I z • z I z • z I z I • z
• uoo.o;o I noo.o;o • noo.ox , • 1100.01.1 I noo.o;o • noo .oio I I 1100.0:0
------------------------•----------1----------1----------1
TEMPERATURE TAKEN I Z I 2 I 2 I----------•----------
2 I 2 It----------t---------------------•-----------
2 I I 2
I l 66. Tl.I I l 66 . 71.1 I C 66. Tl.I I I 66. 71.1 I l 66. 71.1 I l 66. Tl.I I · I l 66. 71.1
------------------------l----------•----------l----------•----------l----------l----------1---------------------1
TEHPERATURE HOT TAKEH • 1 I l I 1 • 1 • 1 I 1 I I
-----------
1
I ( 31.31.1 I t 33.37.1 I ( 33.37. 1 • I 33.JlO I ( 33.]7.I I ( 3].37.1 I I f 33 . JZ I
0
0
-0
rv
-
0
----------
Study 854
PROGRAM: Alum;.Adsorbed Yeast Recombinant Hepatitis 8 Vaccine,
Study 854.

recombinant hepatitis B vaccine 1n the following adult
populations:
1. Chronic carr1ers of HBsAg
2. Healthy Hyporesponders to Plasma-Derived vaccine.
3. Healthy Nonresponders to Plasma-Derived Vaccine.
4. Healthy Transient Responders to Plasma-Derived
Vaccine.

Lot #979/C-KS64 (10 mcg HBsAg/ml)
PRINCIPAL Jules D1enstag, M.O.

Massachusetts Gen. Hosp.
Boston, MA 02114

Mass. General Hosp.
Fruit Street
Boston, MA 02114
Gastrointestinal Un1t
Mass. General Hosp.
Boston, MA 02114

Fruit Street
Boston, MA 02114
DATE INITIATED: October 14, 1984
31261/1
1 /5/86
Study 854
STUDY POPULATIONS: The study populat1on will consist of adults of either

sex (excluding pregnant women) who can be classified
into one of the following groups:
Number of
Group Subjects Qualifications
Carriers 10-15 Chronic carrier of HBsAg for at
least one year, with no signs or
syniptoms of chronic liver
disease, and a stable ALT level
less than 3 times the upper limit
of nomal.
Hypo responders 15-20 Healthy adults who have had only
a low level anti-H8s response
(positive titer obtained in at
least 2 successive bleedings) to
a complete 3 injection regi,aen
of plasma derived hepatitis B
vaccine. [maximum antibody
titer 8-36 when measured in
(b) (4) RIA units, 2.l-9.9 when
measured in tems of S/N ratio,
or <10 mIU/ml]
Non responders 15-20 Healthy adults who had a single

post-vaccination blood sample
with an ant1-HBs titer in the
range S/N e 2.1-9.9 followed by
additional samples all with SIN
less than 2.1 as well as persons
whose post-vaccination blood
samples all had anti-HBs titers
of S/N less than 2.1 after
receiving a three injection
series of plasu-derived
hepatitis 8 vaccine.
Transient 10-15 Healthy adults who had at
Responders least one blood sample with
an anti-HBs titer of S/N >10
following a 3 injection series
vaccine but have subsequently
lost antibody (S/N <2. 1).
31261/2
l /6/86
Study 854
PROCEDURE: Prior to vaccination, each participant will be

screened for HBsAg, ant1-HBc, anti-HBs and ALT level.
A serum pregnancy test will also be performed for all
women of ch1ldbear1ng age. Vaccine is administered
intramuscularly according to the following schedule.
Vaccination Regimen
Carriers 1.0 ml (10 mcg HBsAg) at time 0, 1,
2, 3, 4 and 5 months.
Hyporesponders 1.0 ml (10 mcg HBsAg) at time O
Non responders 1.0 111 (10 mcg HBsAg) at time O, 1

and 6 months.
Transient 1.0 ml (10 mcg HBsAg) at time 0.
Responders
l_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ~
The vaccine rec1pients are asked to record their

note any local or systemic complaints. Unexpected or
serious reactions will be reported to the study
physician inmediately.
Follow-up blood samples will be obtained from carriers
monthly for 6 months and at 9 and 12 months; from
hyporesponders and transient responders at 1, 3, 6, 9,
12 and 24 months and; from nonresponders at 1, 2, 3,
6, 9 months, and at 12 and 24 months from those who
have seroconverted by 9 months. Samples are assayed
for HBsAg, anti-HBC, anti-H8s, and ALT by Dr.
Dienstag. Samples may also be assayed at MSDRL for
yeast antibody and for the proportions of anti-HBs
specific for the! and g determinants of HBsAg.
RESULTS: HYPORESPONOERS:
10 mcg Lot #979/C-K564 at time 0.
1. Number vacc1nated: 2
31261/3
1/6/86
00924
Study 854
RESULTS: (Cont.) 2. Serolog1c Results:

One of the vaccine recipients displayed a marked
boost in ant1-H8s titer one month after receiving
one injection of vaccine (10 mcg HBsAg). The
other vacc 1ne recipient has not responded. The
anti-HBs titers for these two subjects are
presented below.
Pre-vacd nation •-Anti-Mas Titer (mlU/1111) ··-

lr'...11se IJ anti~s Titer 1 fllollth 3 fllonths 6 Months
'6) (6)
6.2 186.8 123.0 39.0
- 2.4 1.5 · o. 1 0.2
Clinical follow-up data are available for both
vacc1nees. One participant had an injection site
complaint and one participant had a systemic
complaint. Refer to Table 2 for a listing of
specific clinical complaints. Temperature data
are provided 1n Table 3.
There were no serious or a tanning reactions
NONRESPONDERS
10 mcg Lot #979/C-K564 at 0, l, and 6 months.
Injection No.
_ 1_ _2_ _ 3_
14 13 13
312&1/4
1/6/86
00925
Study 854
RESULTS (CONT.): 2. Serolog1c Results:

Sero logic data are available for 12 participants at
six months. Fifty-eight percent (7/12) of the
subjects seroconverted (SIN ~2.1) for anti-HBs.
Twenty-five percent (3/12) of the vaccinees
developed protective levels of anti-HBs (mIU/ml ~10)
at that time. The GMT at 6 months for all vacc1nees
was 3.2 mIU/ml and 45.8 for responders (mIU/ml ~10).
Refer to Table 1 for ant1-HBs responses and GMTs for
3. Clinical C011plaints:
Clinical fol low-up data are available for at least
thirteen part1c1pants after each injection. The
below.
Type of ----Frequency in% by InJection-----

Co111Plaint 1 2 3
Injection 21 (3/14) B ( 1 /13) 15 ( 2/13.)

Site
ystemic 14 (2/14) 8 ( 1 /13) 0 (0/13)
Refer to Table 4 for listings of specific complaints

by injection number. Maximum temperature data are
provided in Table 5.
attributable to _vaccine.
TRANSIENT RESPONDERS
10 mcg Lot #979/C-K564 at time 0
1. Number Vaccinated: 3
At one month, two of the transient responders who
were seronegative for anti-HBs prior to vaccination,
31261/5
1/6/86
Study 854
RESULTS (CONT.): seroconverted for ant i-HBs. The G\IIIT for the two
responders was 67 .9 mIU/1111. The anti-HBs titers
for the three subjects are presented below.
Pre-vacci nat Ion Anh-Hlls Titer (11IU/m1)

ca~ D o111t i-Mls Titer 1 flonth
b) (6)
0.2 14.8
0 311. 7
0.4
Cl1n1cal follow-up data are ava11able for all the

part1c1pants. No vaccinee had an injection site
complaint. One subject had a systemic complaint
( Tab 1e 6) . The maximum reported temperature was
99.9•F (Table 7).

PUBLICATIONS: Butterly L, Watkins E, Hinkle CA, Dienstag JL.

Response to recombinant yeast hepatitis B vaccine in
nonresponders to plasma-derived hepatitis B vaccine.
31261/6
l/6/86
Table I
ANTIBODY RESPONSES FOLLOWING VACCINATION WITH ~ECOt18IN~HT HEPATITIS B VACCINE
STUDY 0854
POPULATIOH NotlFIE!PONOEl!S I H I
DOSE 10 NCG
LOT CKS64
REGINm 0, 1, Atl'.l 6 MOUTHS
I X WITH AHTI-HBS I GMT IMIU/MLI I

l---------------------------------------l-----------------------------------------------------1
I I I RESPDtlDERS I
TIME
INONTHSI
l---------------------------------------1-----------------I-----------------------------------I
I S/H >= 2.1 I NIU/ML>= 10 I ALL VACCINEES I S/N >= 2.1 I NIU/Ml>: 10 I
···-···································································-·········*·•·············-················
I I I I I I
l NOHTH I 38% (5/131 I 15Y. (Z/131 I 3.3 I 17.Z I 76.S I
I I I I I I
2 MONTHS I 6T/. 18/121 I 587. 171121 I 18.S I 38.9 I 59.S I
I I I I I I
3NONTHS I 64Y. (7/11) I 'tSX (5/11) I 10.9 I 35.8 I 86.2 I
I I I I I I
6 MONTHS I 58X 17/121 I :?SY. 13/12) I 3.2 I 7.7 I 45.8 I
I I I I I I
9 tlOHTHS f 100?. ( 4/4) f SOY. I Z/4 I I 36. 0 I 36. 0 I 245 .1 I
I I I I I I
·····························································~·····················································
0
0
-.0
....
N
Table 2
PATIENT COUNT CLINICAL COtlPLAINTS

STUOY 0854
TREATHENT
LOT tMfflER CK564
DOSE 10 t1CG
PATIENT CLASS HYPORESPONDERS
I TOTAL VACCIHEES I 2 PATIENTS) • DOSE l •

l----------------------------------------------------------------------------1
CLINICAL
COl1PLAINTS
1----------------------------------------------------------------------------I
I I I 1 I 2 I J I 4' • 5 I
WITH
ICotlPLAIHTS
•••••••••••••••••••••••••••••••••••••••••••••• l•••••••••• l•••••••••••••••••••••I•••••••••• •••••••••••••••••••••••••••••••••
REACTION , LOCAL IIHJECT. SITE I •• l II O •I O •I O •I O •• 0 •I •I l
• ( 50.07.1 I I 0.07.) • ( 0 .0?.I • ( 0 . 07.1 I f 0.07.1 I I 0.01. 1 I • I SD . OX )
-----------------------------------•----------l----------l----------l----------•----------1----------1----------1-----------
soRrnEss • 1 I o I o I o I o I o • I 1
I I so.ox, I f 0.07.1 I I O.OXI I I 0.07.1 If O.OXI • I O.OXI I I I 50 . 0%)
-----------------------------------1----------•----------l----------
sysTEMIC I 1 I 1 I o I
l----------1
o I
----------1----------
o I o ,I
l----------l-----------
I 1
I I SO.DX I I I 50.DXI I I 0.0%1 I I D.DXI I I O. OXI I I D. OXl I I I SO.OX)
I I I I I r
WHOLE BOOY/GEIIERAL I I I l I O I O O I D I 1
I I 0.07.1 I I 50.D?.l I I o.ox, I I 0. 07.1 f D. OXI I I O.OX I I I ,a.ox,
I I I • I I
FATIGUE/WEAKNESS • 0 I 1 I D I D O I I I 1
I ( O. DXI I I 50.0XI I I 0.0:1.1 I I 0 . 0?.) I O. OXI I I 0. 0?.I I i 50.0%1
I I I I I I
RESPIRATORY I l I O I O I O D I o I l
I I 50 . 07.1 I I 0.07.1 I I a.ox, I I 0.07.1 f 0.01.I I I 0.07.1 I
I SD . OX) /
I I I I I I
RHINllI'S I l I O I D I O O I D I l
I I so.o:o I I o.o:o I c o. o;o I , o.o:o , o.ox1 I , o.ox, I I so.ox ,
- ----------------------------------l----------1----------1- - --------l----------l----------l----------l-------·--I-----------
P£RSotlS WITH Cot1PUJNTS I 2 I l I O I O I D I D I I 2
I 1100.D?.1 I I S0.0%1 I I D.07.1 I I 0.07.1 I I D.0%1 I I 0. 0%1 I I 1100 . DXI
-----------------------------------1----------I----------I----------I----------I
PERSONS WITH HO CONPLAIHTS I D I l I 2 I 2 I
----------I----------I----------I-----------
2 I 2 I I D
I I 0.07.1 I I S0.07.1 I 1100.07.1 I 1100.07.1 I 1100 . 07.1 I 1100.or.1 I I I D.OY.I
-----------------------------------1----------l----------l
PERSOHs WITH HO DATA I o I o I
----------l----------l----------l----------l----------l-------
a I o I o I o I I o
----
I I O.OY.I I I O.OY.I I I O.DXJ I I 0.07.1 I I o.DY.I I I 0.07. 1 I I I o.o;o
0
0
.l:J
I\J
or:
,
Table 3
PATIENT COUNT NAXIl1Ul'1 TENPEAATURES
RECottBlNANT HEPATITIS B VACCitlE
STUDY 08S4
TAEATHENT
LOT tM1BEA CK564
DOSE 10 HCG
PATIENT CLASS HYPORESPOHDER9

I•---------------------------------------------------------------------------------------1
DAYS POST VACCIHATlOH I Nll18EA
IUX TEHPEAATURE
fDEG F, OAALI
•---------------------------------------------------------------------------------------1
• 0 I 1 • 2 • 3 • 4 I 5 • • •
WITH
HAX TEHP
························•··········•··········
• I •··········•··········
I • ···········•···········································
• • • •
< 99 • 2 I z • z I z • 2 I 2 • • 2
• 1100.ox, • 1100.ox, I c100.ox, I 1100.ox, • 1100.07.1 I c100.ox, • I 1100.01.1
------------------------1----------
TEHPERATUAE TAKEN • Z
l-----·----l----------l----------•----------l----------•---------------------l--------·---
• 2 I 2 I 2 I 2 • 2 • I 2
• 1100.07.1 • 1100.01. , I c100.07.1 • 1100.01.t • 1100.07.J • ClOO.OY.J I I 1100.~1.1
------------------------•----------
TEHPEAATURE NOT TAKEN I O I
l----------l----------
o I O
l----------l----------
• 0 I O I
1----------1---------------------
O I
I-----------
• 0
I I 0.01.1 I I o.ox, I c 0.07.1 I I 0.01.1 I I 0,07.1 I c 0.07.1 I I t ~.07.1
0
0
-D
N
·•
"'
Table 4
PATIENT CO\MT CLINICAL Cot1Pl l IHTS

RECOIIBINANT HEPATITIS B VACCitlE
STUDY 0854
TREATMENT
LOT NUMBER CK56'+
DOSE 10 MCG
PATifUT CLASS NOtlRESPOtl>fRS I HJ
------------------------------------------------------------------------------------------------------------------
I TOTAL VACCJHEES ( 14 PATIENTS) - DOSE l I
.---------
l----------------------------------------------------------------------------1
I DAYS POST VACCIHATIC>I I Hllt18ER
CLINIC AL
C0MP LA IJITS
l-~--------------------------------------------------------------------------
I O I 1 I 2 I 3 I 4 I S I 1 MITH
ICOt1PLA I NTS
aaa••••••••••••••••••••••••••••••••l••••••••••l•••••••••• l•••••••••• l•••••••••• l••••••••••l•••••••••• l••••••••••I ••••••••••
I I I I I I I I
RU CTION, LOCAL IINJECT. SITEJ I 1 I 2 I 2 I O I O I o I I 3
I I 7.Uo I 1 14.3%1 I r 14.3%1 I I 0.0%1 I l o.o:o I l o.ox 1 I I c 2l . 4Y. J
-----------------------------------
IHFLA11t1A TIOH
l----------l----------1----------l----------1----------
I o I l I o I o I o I
I----------I----------
o I
I-----------
I 1
I r 0.0:1.1 I c 1 .1:1.1 I 1 11.0:0 I I o.o:o I t o.o:o I c 0.0%1 I I 1 7 .1x1
I I I I I I I I
SORENESS I 1 I 2 I 2 I o I o I o I I l
I ( 7 . 1:I.I I l 14.]1.) I ( 14.31.1 I I 0.0%1 I I D.01.1 I l 0.0%1 I I l 21.4X I
-----------------------------------t----------
s 1snt11c I D
l----------
I O
l----------l----------l----------l----------l----------l-----------
I O I 1 I O I l I I 2
I r o . O%J I l o . O?.J I l 0.0%1 I 1 7.1%J I I 0.01.1 I r 1.11. 1 I I I 14.31.1
--------------------------------------------------------------------
1
---------- -----------------------------------------
I
---
WltOLE BODY/GENERAL I D O O 1 0 I I 1
I I 0 . DlO C 0.01.J l o.o;o I 7.1%) I 11.o;o I 0.0%) I I 7.11.1
I I
FATI GUE/WEAKNESS I D O D 1 0 0 I 1
1c o.o:r., c o.Dt t c o.ox1 c 1.1:t.1 r o.o;o I o . ox , I r 1.1:t.t
I I
HEADACttE I D O O 1 0 0 I l
I C D.OXI l 0 .07.) I 1 .0%1 I 7.11.) ( o.o;o I o.o;o I l 1.1:0
I I
DIGESTIVE SYSTEM I 0 D 0 D 0 1 I 1
I l O. ox I c O. 01. J C O. 07.1 I O. 0% I l O. 01. I I 7 .1;0 I I 7. li! I
I l
HAUSE A I D II O O O 1 I t
·I l 0.0% 1 l 0.07.I I l 0.01.1 I 1 .01.1 l 0.01.1 I 7 . 11.1 I l 7.li!I
-----------------------------------l----------
P!RS~ WITH COMPLAINTS I 1
l----------l----------l----------l----------1----------1----------1-----------
I Z I 2 I 1 I O I 1 I I 5
I C 7.UO I l 14.31.) I ( 14.li!) I I 1.1:0 I C o.oxt I I 7.1:1.1 I I l 3§ . 7:1.)
----------------------------------- Il----------l----------t----------l----------l----------l----------1----------1-----------
PEAS0t1s wn11 HO c0t1PLAIHTS n I 12 I 12 I n I 14 I u I I 9
I ( 92.9%) I ( 85.7%) IC 85.7r.l I I 92.91.) I uoo.o;o I < 92.9% ) I I I 64 . ]%1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH NO DATA I Cl I O I O I O I O I I ., I 0
I 1 0.0:t.1 I r 0 . 0:1.1 I c 0 . 0:1.1 I 1 0.0%1 I c a.0%1 I I o.ax, I I 1 0.0:t.1 0
0
~
UI
0
"
Table 4 (cont)
PATIENT COU'IT CLINICAL COMPLAINTS

RECOl18INANT HEPATITIS B VACCIUE
STUDY 0854
TRE ATttENT
LOT NVl1BER CK564
DOSE 10 t1CG
PATIEHT CUSS tlOIIRESPOHDERS I H)
I TOTAL VACCitlEES I 13 PATIENTS) - DOSE 2 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION • NUt18ER
CLINICAL
COt1PLAttUS
l----------------------------------------------------------------------------
• 0 • l I 2 I 3 I 4 I 5 I
1 WITH
ICOt1PUINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l•••••••••• l••••••••••••••••••••• l••••••••••I•••••••••••••••••••••
I I I I • I • •
REACTION, LOCAL IINJECT . SITE I I O I l I l I O I O I O I I l
I I 0.0%) I I 7 . T/.) I I 7.7%) I I 0.0%) I I 0.0% ) I I 0 . 0%) I I t 7.7%)
-------------------------------
so11EHESS
· -- Il----------
O
l----------1
I l I
----------1
l I
----------l----------l----------
O I O I O
l----------1-----------
I I l
I , o.o;o I , 7.n, I 1 1.1:1.1 I I o.ox, I I o.o:o I , o.ox, • 11 1.n,
-----------------------------------1----------1----------l-------·--1----------1----------l----------
sysuttic I O I O I O I O I l I O I
l----------l-----------
I 1
I I 0.0%1 I I D.0%) I I 0.0%1 I I 0.0%1 I I 7 . 7%1 I I o.ox1 I I t 7 . 7% 1
----------------------------------------------------------------------------------------------------------------------------
1 I I I I I I I
IUSPIRATORY I O I O I O I O I 1 I O I I 1
I I o.o:o I I 0.0%) I I 0.0%1 I I o.o:o I I 7.7%) I I 0.0%) I I t 7.7%1
I I I I I I I I
PHARYNGITIS ISORE THROATI I O I O I O I D I 1 I O I I 1
I I o.0%1 I I 0.0%1 I I o.O%l I I 0.07.l I t 7.7% l I I o.ox, I I t 7.7%t
I I I I I I • •
UPPER AESPIIUTORY INFECT., NOS I O • o I O I 0 I l I 0 I I l
I I o. ox, I I o. ox, I I o. ox, I , o. o;o I t 7. n I I , o. ox 1 • I 1 7. n 1
-----------------------------------1----------I--------•.
PERSONS Wlm CotlPLAINTS I O I l
l----------l----------1----------1----------1
• l I O I 1 I D I
---------- II-----------
t
I I 0.07.l I ( 7.no . I 1.1;0 I I 0.0%1 It 7.no I I o.o:o I I l 15.4%1
-----------------------------------1----------l----------•----------l----------•----------•----------
PERsONs WITH NO c0'1PLAINTS I n I u I 12 I 13 I 12 I n
l----------•-----------
I I u
I 1100.0;0 I I 9Z.3iO I I 9Z . 3Xl I 1100.0;:1 I I 9Z.3%t I 1100.0;: 1 I I I 84.6iO
---------------- -------------------1------ ----I----------I----------I----------I----------I---------- I ---------- I -----------
PEAsotis WITH NO DATA I o I o I o I o I o I o I I o
I c o. o;: I I « 1 . ox I • I o. oz l I t o. 01.1 I l o. o;: I I I o. oz I I I l o. o:o
0
0
-0
\.,of
.,
Table 4 (cont)
REC0t18INANT HEPATITIS 8 VACCINE
STUDY 0854
lRU111ENT
LDT t1Ull8U Cl<564
DOSE 10 IICG
PATIENT CLASS tlOIIIIESPONDERS I H)
----------------------------------------------------------------------------------------------------------------------------
I lOlAL VACClHEES I 13 PATIEITTSI - DOSE 3 I
1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I tlUNBER
CLINICAL
COMPLAINTS
l----------------------------------------------------------------------------1
I O I 1 I Z I 3 I 4 I 5 I
WllH
ICDl1PLAIHTS
a••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION. LOCAL (INJECT. SITE I I 1 I Z I 1 I l I O I O I I 2
I l 7.77.J I I lS.41.1 I l 1.11.1 I l 7.7i0 I l 0.01.J I l 0.0:1.1 I I l 15.41.t
-----------------------------------l----------l----------l----------l----------l----------1----------1----------1-----------
soRENESs I O I l I l I O I O I O I I l
I ( 0. 0?.) I ( 7. 7l I I ( 7. 7?. t I ( 0. OY. I I ( 0. O?. I I ( 0. GY. J I I ( 7. 7?. I
I I I I I I I I
OTIIER I l I 1 I O I 1 I O I • I I 1
I c 7. 7?. J I 1 7. 7Y., I c o. 01. 1 I , 7. 1:1. 1 I , o. 01. 1 I I
I 1 1. 11., o • o;o I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOtlS WllM CotlPUIHTS I 1 I Z I 1 I l I a I O I I Z
I 1 1.11.1 I , 15.4:t.l I c 1.1:0 I c 1.1:t.1 I c 0.01., I t o.o;o I I 1 1s.4:1.1
-----------------------------------1----------1----------I----------I----------I----------I----------I----------I-----------
PERsotlsWITH NO Cot1PLAINTS I 12 I 11 I 12 I 12 I ll I 13 I I ll
I , 9Z.l:t.l I c 8'4,6:t.t I t 92.11.1 I l 92.JY.I I uoo.o;o I noo.0:1.1 I I c 8•L6%1
-----------------------------------t----------1----------1----------1----------l----------l----------l----------1-----------
Pnsous MITH HO DATA I O I O I O I O I 0 I 0 I I G
I I O. OY. I I I O. OY. I I l O. OY. I I l O• OY. I I I O. DY. I I l O• OY. I I I l O. 0:1. I
0
0
.0
""
N
.,
Table 5
PATIENT COUNT HAXI11Ut1 TEMPERATURES
RECOf18IHAHT HEPATITIS B YACCIHE
ST\IOY : 0854
TII U TNENT
l Ol HUt19ER CK561t
DOSI!'. 10 ttCG
PATIENT CLASS: NOHRESPONDERS IN )
I lOTAl VACCIHEES I 14 PATIEHTSJ - DOSE 1 I

Il---------------------------------------------------------------------------------------
DAYS POST YACCIHATIOH 1I HUt18ER
MAX TEMPERATURE
COE& F, OII ALI I
l---------------------------------------------------------------------------------------1
O I 1 I t I l I 4 I S I I
MITH
I NAX TEHP
~••••••••••••••••••••••• Il••••••••••l••••••••••l••••••••••
I I
l•••••••••• Il•••••••••• Il•••••••••• I•••••••••••l•••••••••• •I••••••••••
I
< 99 I 13 I 11 I 11 I u I 14 I 14 I • 9
I C 92.<J:O I C 78.E,Z) I C &4.6i0 I C92.9:0 I 1100.0:0 I UDO.OZ) I I C64.3¼1
I I I I I I I I
99 - 99.9 I 1 I 3 I 2 I 1 I o I o I I s
IC IC7.lX) I(
21 .4ZI IC 1S.4ZI I O. OZI I t O. DX) I
7 . lZ) I I ( 35.7¼)
------------------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TE11PERATURE TAKEN I 14 I 14 I 13 I 14 I 14 I 14 I I 14
I 1100.oz, I noo .o;o I ( 92.9Z I I (100.0Z) I (100.0XI I UDO.OZ) I I CIOO.OZI
------------------------l----·-----I----------I----------I----------I----------I----------I---------------------I-----------
TEt1PERATURl NOT TAKEN I o I D I 1 I D I o I D I . I O
If O.DZJ I ( O. OXI I I 7. l ZI I ( D.OXI I I O.DXI I I O.OZI I I ( O.DZI
0
0
.t)
l>I
l>I
e
Table 5 (cont)
PATIENT CIXMT HAXIHUn TEHPERATURES
STUOY 0854
TRUTt1EHT
LOT tM1BER CK564
DOSE 10 11CG
PATIENT cus,·: NOl~ESPOHIJERS IHI
I TOTAL VACCINEES I ll PATIENTS! - DOSE 2 I

1---------------------------------------------------------------------------------------I
I DAl'S POST VACCINATION I NU18ER
Hl X TEHPERATURE
IDEG F ,ORALI
l-------------------------------•-------------------------------------------------------1
I O I I • 2 I 3 • ~ IS • I
WITH
.HAXTEHP
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••••••••••••• l••••••••••l•••••••••••••••-•••• l•••••••••• I••••••••••
< '19
I
• • I• 12 I• 11 I• a •I 9
•I 10
•I II 6
I I e1.aY.1 I 1100.0;0 I • 91.no I 1 66. no I c 75.01.1 I I a:s.1Y.1 f I , so.07.1
I I I I I I I I
99 - 99.'I I t I o I 1 I 4 I l I 2 I I 6
I C 18.2;0 I C 0 . DlO I I 8 . 3i0 I I l3 . 3i0 I ( 25.0iO I I 16.77.) I I C SO.DZ)
------------------------l----------•----------t----------l----------l----------l----------1
TEHPERATURE TAKEN I 11 I 12 I 12 • 12 I 12 I 12 I
--------- .-----------1-----------
' I 12
I C 8ft. 6,0 I C 92. llO I I 92 • 3i0 I I 92. 31.1 I I 92. 31. I I I 92 • lY. I I I I 92 • 3Y. I
------------------------1----------1----------t----------l----------l----------l----------l--------~
TENPUATURE NOT TAKEN I Z I l I l I l I l I l I
-----------1•-----------
l
I I 15. 4Z J I I 7. 7i0 • I 7. T.1.1 I ( 7. 7Z I I I 7. 71.1 I I 7. 7Z I I I I 7. no
0
0
.()
vol
.c,
•
Table 5 (cont)
PATIEHT COUHl "AXIHU1 TEnPERAlURES
RECOt18INAHT HEPATITIS 8 VACCINE
STUDY 085ft
TREAffltNT
LOT M.JttBER CKS6't
DOSE 10 HCG
PATIEHT CLASS HONRESPOHDERS CH I
----------·--------------------------------------------------------------------------------------------
I TOTAL VACCIHEES I 13 PATIEHTSI - DOSE 3
- -- -I -
1---------------------------------------------------------------------------------------
I DAlS POST VACCIHAT10t4 I• HU18ER
11AX TEnPERATURE
I DEG F, ORAL I
l---------------------------------------------------------------------------------------1
I O I 1 I 2 I 3 I It I 5 I I
WITH
I HA)( TEHP
••••••••••••••••••••-••l••••••••••l••••••••••••••••••••••••••••••••l•••..••••••••••••••••l•••••••••••••••••••••I••••••••••
• I I I I I I I
< 99 I 10 I 12 I 11 I 12 I 12 I 11 I I •
I I 76. 91. t I ( 92 . 3l0 • ( 91. 7Y. t I l 92. liO I l 92 . llO I I 91. 7Y.) I I C 69. 2)0
I I I I • I I I
99 - 99.9 I Z I 1 I 1 I 1 I 1 I l I I 3
I I 1s.1t;o I I 7.7l0 I I 11 . 31.t 11 7.7,0 I l 7.7r.l IC 11.l,0 I IC 23.liO
I I I I I I I I
100 - 100.9 I 1 I o I o I o I o I o I I 1
I 1 7.7,o I c o.o;o I< o.o;o l c o.oz1 l c o.o:o • c a.oz, • I , 1.1;0
------------------------ Il----------l----------l----------l----------
TEHPERATURE TAKEN ll I 13 • 12 I 13
•----------
I 13
l----------1---------------------1-----------
I 12 I I 11
I 1100.0;0 I c100 .Dl!, I , 92. Jl! I I uoo.ol!I l non .Dl! 1 I , ,2 .1;n • I 1100 . oY. l
------------------------ Il----------1
TEHPERATURE HOT TAKEN O I
----------
O I
l----------
l
l----------1----------1----------1---------------------I-----------
I O I O I 1 I I O
11 o.ol! t I c o.ol!l • , 7.77.t l c o.o;o • c o.o;o I c 7.7i:t I I, o.oio
0
0
..0
1.,,1
\JI
~
Table 6 (cont)
PATIENT COUNT CLINIC AL COl1PLAINTS

REC0118IHAtfT HEPATITIS B VACCINE
STUDY 11854
TRUTt1EMT
LOT HUMBER · cK5&4
OOSE 10 t1CG
PATIENT CLASS TRAl~S U:NT RESPOMlERS
I TOTAL VACClNEES I 3 PATifHTS) - DOSE l I

1----------------------------------------------------------------------------I
I . OAYS POST VACCINATION I HUtfflER
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------I
I O • 1 I 2 I 3 I It I 5 •
MITH
ICOMPLA IHTS
••••••••••••••••••••••••••••••••••••••••••••••l•••••••••• l••••••••••l•••••••••• l••••••••••l•••••••••••••••••••••I••••••••••
-----------------------------------1----------•----------l----------•----------l----------t----------l----------l-----------
sYSTEHIC I o I o I 1 I o I o I a I I 1
• C o . o;o I I 0.07.1 I C 33 . 37.1 • C 0.07.1 I C o.o;o I ( 0.07. 1 • • ( 33.37.1
I
t'IUSCULOSKELETAL I O I O I l • 0 I O I O I I 1
0 . 07.1 I I 0.07.l I I 33.37.l I I 0.07.1 I C 0.07.I I I 1.07.l • I C 33.17.>
I I I I I I I
HIP PAIN • a I o I 1 I o I o I a I I 1
I c 0.01.1 • c 0.01.1 I c 11.1;:1 I c o.o;o I c 0.0;:1 • c I c 11.11. 1 0.01.1 •
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONs wnH conPLAINTS • o I o I 1 • e I o I o I I 1
I ( 0.07.1 I I 0.117.l I ( 33.]7.l I ( 0.07.I I ( 0.07.1 I C 0.0)0 I I C 3].]1/. J
-----------------------------------1
PEASOHS WITII NO COMPLAINTS I
----------
l
t----------l----------l----------l----------l----------1----------I-----------
I 3 I 2 I J I 3 I 3 I I t
I c100.07. 1 I c100.07.1 I c 66.77.1 I 1100.07.1 I 1100.01.1 I 1100.0;:1 I • r 66.r1.1
-----------------------------------1----------l----------l----------l----------1----------•----------I----------I-----------
PEASous WITH NO DATA I o I o I o I o I o I o I I o
I c o . o;o I , o. 0:1.1 I I o . o;: 1 I I o . o:o I I o. 07.1 I I o. o;o • • c o . 07. 1
0
0
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~
0-
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Table 7
PATIENT C0UNT HAXIlfJH TEHPERATURES
REC018INAHT HEPATITIS 8 VACCINE
STUDY D8S4
TRE ATt1ENT
LOT NU!l!ER Cl(S64
DOSE 10 MCG
PATI ENT CLASS TRANSIENT RESPONDERS
f TOTAL VACCIHEES I 3 PATIENTS! - DOSE l I

1I ---------------------------------------------------------------------------------------I
HAX TEHPERATURE
CDE6F,ORALI
l---------------------------------------------------------------------------------------1
f O I 1 I Z I l I 't I 5 I I
MITH
l 11AXTEl1P
••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l•••--•••••l••••••-•• l••••••••••l•••~•a••••
I I I I I I I I
< 99 I z I 1 I 1 I z I 1 I 1 I I z
I I 66.T/. t f 1100 . 0;0 f 11 00.D1. ) I 1100.01., I 1100.01.) I 1100.01., I ·I I 1>6 . 7"/. I
I I I I I I I I
99 - ,, •9 I 1 I o I o l o I o I o I I 1
I c n . 1;O t 1 0.01., I • o.o;o I c o.oio I I o.o;o I c o.o;o 1· I c n. 1:1.1
------------------------ Il----------
TE11PERAT\JRE TAKEN 1
l----------
I l
l----------
I l
l----------
I Z I
t----------1----------1
l I l I
---------------------I-----------
I l
I noo.o:o I 1100.0lO I (100.0lO I t 66.7)0 I uoo.or. , I 1100.0;0 I ! 1100.0:0
------------------------ Il----------
TEHPERATURE HOT TAKEN O I
l----------
O I
l----------l----------l----------l----------1---------------------1-----------
O I l I O I O I I O
I I O.OlO I I o.o;o IC 0.01.l I ( 33.3:O I I o.o:o I I 0.0Y.) I I C o.o:o
Q
0
.0
...,
l,j
...
244 R~S?ONS~ TO IU:CO!"'~INANT Y~ST H::?ATIT!S B VACC!Nt: IN
NONR..:S?O~"OE~S TO PL,'1.SMA-D£RIV.:O HEPATITIS B VACCINE
L B~tte=lv, E Watkins, C~ Hinkle and JL Dienstaa.
Cast=oin:estinal Unit, Massachusetts General Kospitel,
Jloston, MA.
P=eli::>.inary reports suggested that recOJnbinant yeast
hepatitis B vaccine (R-HBvac) kiqht be 1110re il:llllunogenic
Ulan the t=iply inactivated plasma-derived hepatitis B
vaccine [?-1!!3vac) (Hepatoloqy 1984; 4: 1077) • Therefore,
to test this hypothesis, ve ac!Ainistered three 10 ~9 doses
of R-1!:!lvac (Merck Sharp, Dohme Research L&b0ratoriesl at
ti.me 0, l, and 6 1110nths to 14 normal adults vho had failed
to resyond to one or 1110re courses (3-6 doses) of P-H:Bvac.
The frequency II positive/I vaccinated] (~) and geometric
meen titer (mIU/mll of anti-HBs responses were as follows:
Month l 2 3 6
anti-!UU+ 5/13 (39) 8/141 (S 71 7/14 (50) 7/lJ (541)
GMT! SO 17 ! 7 J9 ! 10 36 ! 23 8 :! 7
For c0111parison, the same data are charted belov for 65

seronegative health vorkers, never previously vaccinated, ·
after receiving R-Hllvac:
Month 1 2 3 6
anti-HBs+ 26/65 (38) SJ/62 (86) 61/65 (94) 60/62 (97)
GMT ! SD 7 ! 4 JB ! 4 so! 4 72 ! 4
The me&n ! SO &ges of the 8 initial nonresponders vho

ultiMl.tely did respond and the 6 vho did not vere ind1s-
tinguisb&ble, 38 ! 8 and 411 ! 15. The response to R-HBvac
in almost 60\ of nonresponders to P-HBvac appeared
prom.isin~. especially vpen compared vith a ~o, rate of
low-level, poorly sustained &nti-KSS responses in P-KBva.c
nonresponders given a second course of P-HBvac
[Hepatoloqy 198414:1077); however, the level of
&n~ibody fell substantially by six aonths, vhen 11«&sured
just prior to the booster injection. Additional follow-up
vill be necessary to detet111ine whether the antil>ody
response to R-KBvae in nonresponders to P-ijBvac increases
and is sustained after booster ~i&ation.
Butterly L, Watkins E, Hinkle CH, Dienstag JL. Response to recombi-

nant hepatitis B vaccine in nonresponders to plasma-derived
hepatitis B vaccine. Hepatology 1985; 5:1007 (abstract),
\
Study 874
Study 874.
recombinant hepatitis 8 vaccine in healthy adults who
failed to develop antibody (nonresponders) or
developed only low levels of antibody (hyporesponders)
in response to three or four injections of
plasma-derived hepatitis B vaccine.
VACCUIE: Yeast Recombinant Hepatitis B Vaccine

Lot 978/C-K 563 (10 mcg HBsAg/ml)
PRINCIPAL Myron Tong, M.D., Ph.O.

INVESTIGATOR : Department of Medical Education
Huntington Memorial Hospital
100 Congress Street
P.O. Box 7013
Pasadena , CA 91105 - 7013
SECONDARY Deborah Roskamp, R.N.

INVESTIGATORS: Liver Center
100 Congress Street
P.O. Box 7013
Pasadena, CA 91105 - 7013
STUDY LOCATION: Liver Center

100 Congress Street
P.O. Box 7013
Pasadena, CA 91105 - 7013
DATE INITIATED: September 1985.

DATE COMPLETED: In progress .
STUDY POPULATION: Participants in the study will be healthy adults of

either sex (pregnant women excluded) who failed to
develop antibody (S/N <2.1) or had very minimal
antibody development (S/N 2.1-9.9) after receiving
three or four injections of plasma-derived hepatitis B
vaccine. Approximately 40 persons will be enrolled.
31291/1
l /6/86
Study 874
PROCEDURE: Each partidpant wi 11 receive a 1 ml injection of vaccine

1n the deltoid muscle at 0, 1, and 6 months. Study
participants will be asked to take and record their body
temperature for five days after each inject ion of vaccine
and to record any local or sys-temic complaints. They will
also be asked to notify the study investigator 1nuned1ately
if an unexpected or serious reaction occurs.
Blood specimens wi 11 be obtained prior to vaccination and

at 1, 2, 3, 6, and 8 months postvaccination. Additional
samples will be obtained at 12 and 24 months from those who
have seroconverted by eight 1110nths.
All blood samples will be assayed for HBsAg, anti-HBc,
ant1-HBs, and ALT. Testing will be perfomed at Huntington
Memorial Hospital and the Medical Laboratory Network. Some
samples 111ay be assayed for yeast antibody and anti-HBs
subtype specificity at "SORL.
RESULTS: NONRESPONOERS/HYPORESPONDERS TO PLASMA-DERIVED VACCINE

10 mcg lot #978/C-K563 at O, 1, and 6 months
Iniection No.
_ 1_ _ 2_ _3_
26 26 0
At one month, 36% (9/25) of the vaccinees
seroconverted for ant1-HBs (S/N ~2. l). Further
serologic data are not available.
3. Clinical Complaints
A sununary of . frequencies of clinical complaints is not
yet available. However, no serious or alarming
adverse events attributable to vaccine have been
reported. Vaccination and follow-up continues in
progress.
31291/2
1 /6/86
Study 875
PROGRAM: Alum-Adsorbed Yeast Recombinant Hepatitis B vaccine,
Study 875
PURPOSE: To evaluate antibody and clinical responses to

licensed hepatitis B vaccine (Heptavax-8) and yeast
recombinant hepatitis B vaccine in renal dialysis
patients who have already failed to develop antibody
after receiving three injections of HEPTAVAX-B.
VACC IN£: Yeast Recombinant Hepatitis 8 Vaccine

Licensed Vaccine (Heptavax-B)
Lot #2277K (20 rncg HBsAg/ml)
PRINCIPAL Theodore L. Johnson, M.D.

INVESTIGATORS: The Duluth Clinic, ltd.
400 E. Third Street
Duluth, MN 55805
Richard N. Hellman, ~.D.
The Duluth Clinic, Ltd.
400 £. Third Street
Duluth, MN 55805
Mark R. Eckman, M.D.
The Duluth Clinic, ltd.
400 East Third Street
Duluth, MN 55805
SECONDARY Pamela Elde, R.H.
INVESTIGATORS: Miller-Dwan Medical Center
502 East Second Street
Duluth, MN 55805
Gayle Gilmore, ·R.N.
Miller-Dwan Medical Center
Duluth, MN 55805
STUDY LOCATION: Miller-Dwan Medical Center
Duluth, MN 55805
2407 I/1
12/31 /85
Study 875
DATE INITIATED: June, 1985
DATE CO~PLETED: In progress.
STUDY POPULATION: Adult patients who are receiving dialysis treatments

for end stage renal disease and have failed to develop
anti-HBs following administration of p1asma-derived
hepatitis B vaccine (HEPTAVAX-8) are el1gible for the
study. Prospective subjects must not be pregnant,
must be negative for HBsAg, ant1-H8c, and ant1-HBs,
and Must have a normal ALT. Approximately 40 patients
will be enrolled 1n the study.
PROCEDURE: Prior to administration of the 1st injection of

vaccine. participants will have a blood specimen
obtained and tested for HBsAg, ant1-HBc, ant1-HBs and
ALT.
Participants will be assigned to one of the following
groups:
Group Vaccine
Plasma vaccine (HEPTAVAX-8)
2 Yeast Recombinant vaccine
Participants will also be distributed between the

groups with respect to sex and 10 year age strata
(i.e .• 30-39, 40-49, etc.).
Each subject wi 11 receive 2 - 1.0 111 (40 mcg HBsAg)

intra11uscular injections of HEPTAVAX-8 (Group 1) or
the yeast recombinant vaccine (Group 2) at 0, 1, and 6
months. Vaccinees w111 be asked to take and record
their temperatures for 5 days after each injection and
record any local or systemic complaints that they have.
Follow-up blood samples will be obtained at 1, 2. 3, 6
and 8 months following the first injection of
vaccine. All samples will be tested for HBsAg.
anti-HBc, anti-HBs, and ALT. Assays for ALT will be
done in Duluth, Minnesota. All other assays will be
24071/2
12/31/85
Study 875
PROCEDURE: (Cont.) done by the Merck Sharp and Dohme Research

Laboratories (~SDRL).
RESULTS: DIALYSIS PATIENTS (Nonresponders to HEPTAVAX-8):
40 mcg Lot 993/C-K937 (Yeast Recombinant) at 0, 1, and
6 months
40 mcg Lot 2277K (Licensed) at 0, l, and 6 months
Injection No.
Vaccine _l_ ~ _3_
Yeast Recombinant 17 15 0
Plasma-Der1 ved 18 17 0
Two 110nth serologic data are ava11able for 13
participants who received yeast recombinant
hepatitis B vaccine. Seroconversion for anti-HBs
(S/N ~2.1) at two months was 38% (5/13). Fifteen
percent ( 2/13) of these vacc 1 nees developed
protective levels of anti-HBs (mIU/ml ~10) at
that time.
The GMT at two months for all subjects who
received yeast recombinant vaccine subjects was
1.4 mIU/ml and 70.7 mIU/ml for responders with a
titer of mIU/ml ~10.
Two 110nths serologic data are available for 15
subjects who received plasma-derived hepat1t1s B
vaccine. Forty-seven percent (7/15) of the
participants seroconverted (S/N ~2.1) and
developed protective levels of anti-HBs (mlU/ml
~10) at two months.
The Gf!IT at two months for all vaccinees ~as 5.1
mIU/m 1 and 131 . 6 mIU/ml for responders w1 th a
titer of mIU/ml ~10 ..
24071/3
12/31 /85
Study 875
RESULTS (CONT.): Refer to Table 1 for ant1-HBs responses and GMTs

through two months of follow-up.
Two participants who received yeast recombinant
hepatitis-8 vaccine and one participant who
received plasma-derived vaccine were found to have
low positive anti-HBs titers prior to
vaccination. All three participants had a >4-fold
rise in their anti-HBs titers one month after
their first injection of vaccine.
Clini-cal follow-up data are available for at least
15 participants from each vaccine group after the
first and second injections. The overall
frequencies of complaints are presented below:
Type of Frequency in \ by Injection No.

_9!,>1&int __1_ _l__ 3
Yeast RKa,t,foanl Injection Site 12(2/17) 0(0/15)

Syst.anic 29(5/17) 13(2/1S)
Ptasma-Oer\ved Injection Site 13(2/16) 0(0/15)

Systaic 31(S/16) 7(1/15)
Refer to Table 2 and 3 for listings of specific

temperature data are provided in Tables 4 and 5.
ALT Elevations:
Two participants had elevated ALT levels (1 .5 to 2.0
tiraes the upper limit of normal) prior to
vaccination. They remained elevated at one and two
110nths post the initial vaccine injection. Neither
patient was seropositive for HBsAg or anti-HBc.
One subject developed an elevated ALT level (1.5 times
the upper 11m1t of norma 1) one month post the second
injection of plasma-derived hepatitis-a vaccine. He
was seronegative for ant1-H8c, HBsAg and antt-HBs at
that time. Additional serum sa~ples are pending.
24071/4
12/31 /85
OOQ45
Study 875
RESULTS (CONT.): Reactions Reported to the OoBRR:

Three participants withdrew from the study due to
clinical complaints following one injection of vaccine.
l. A 32-year old male who received two 20 mcg
injections of yeast recombinant vaccine (one
injection into each deltoid) developed a swollen,
sore and stiff left arm after administration of
the vaccine. The swelling and soreness persisted
for one week and then subsided. No treatment was
necessary. The subject recovered.
2. A 70-year old male reported becoming 1 111 1 after
receiving two 20 mcg injections of Heptavax-8 (one
injection into each deltoid). The participant was
hospitalized. The study investigator considered
the illness unrelated to vaccine.
3. A 72-year old male developed generalized achiness
and a headache three days after administration of
his first injections of yeast recombinant
vaccine. Forty-eight hours after onset of those
symptoms, he developed a flu-like syndrome with a
temperature of 1oo•F.
There have been two deaths among the study
participants unrelated to vaccine administration.
1. A 53-year old female hemodialysis patient with an
18 month history of widely metastasized
adenocarcinoma of the breast in addition to
chronic obstructive pulmonary disease,
hypertension, and uremic pericarditis, died 6n6l
days after administration of the second injections
of Heptavax-B. Death was due to respiratory
failure. The study investigator did not consider
the death vaccine related.
2. D 6) days after administration ef the second
injections of yeast recombinant vaccine, a 66-year
old female dialysis patient was hospitalized for
an infarcted bowel. Exploratory surgery was
performed and the (b) (6) the patient
expired.
24071/5
12/31 /85
Table 1
Antibody Respon~ Arlong Dialysis Patients Follo:,ing Vacch'li.t ion 1111th

40 mcg ln~tlons of Yeast RecanbiMnt Hepatitis 8 Vaccine
lot 1993/C-1(931 or Pla51111-D!rlved Hepatitis 8 Vaccine
lot 12211K at o. I, and 6 llonths In Study 875
40 mcg (Yeast Recaminantl 40 IIIC!I (PlaSIM-Oerivedl

tl!T C..IlV!!] I GIIIJ {111ItV111I l
Till!! \ t1ith Anti-Kls All Aes11oode" \ with Anti...Jes All Aesoonden
{Flonths) SIN~ 2.1 IIIIU/111 ~ 10 vaccinees SIN~ 2.1 IIIIU/1111 ~ 10 SIN ~ 2.1 lllllV•l ~ 10 vacclnees S/M ~ 2 .1 IIIU/111 ~ 10
--
7.7(1/13) 0(0/13) 0. 4 1.0 ---- 50(7/14) 36(5/14) 3.4 31. 4 103.5
2 38(5/13) 15(2/13) 1.4 12.0 10.1 47(7115) 41(7/15) 5. 1 131.6 131.6
2<1011/6
12/31/85
0
0
.0
""0-
Table 2
RECOt1BINANT HEPATITIS 8 VACCINE
STUDY 0875
TREATNENT
LOT NUt18ER CK017
DOSE 40 MCG
PATIENT CLASS HOtlRESPOHOERS (0)
I TOTAL VACCINEES ( 17 PATIENTS) - DOSE l I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I HUMl!ER
CLINICAL
COHPLAINTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I l I 4 I 5 I
WITH
I COMPLAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l•-•••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION, LOCAL IINJECT. SITEJ I 2 I 1 I o I o I o I 1 I I 2
I , 11.er.1 I , s.97.1 I I o.or.1 I , o.or.1 I , o.or., I , S.9Y.I I I , 11.81.,
-----------------------------------l----------l----------l----------l----------1----------t----------l----------1-----------
s011eNEss I 1 I 1 I O I O I O I 1 I I 2
I I S.97.1 I I 5.9r.J I I o.or.1 I l o.oY.1 I t 0.01.1 I t 5.9Y.) I I t 11.8?.)
I I I I I I I I
STlFFNESS/TlGHTNESS I 1 I l I O I O I O I 1 I I l
I I · 5. 9Y., I l 5. 9Y. I I l o. ox> I t o. o;o I t o. or.> I t 5. 97.1 I I I 5. 97. >
----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sYSTEttIC I 1 I o I 2 I J I 1 I 2 I I s
I I 5.9Y.) I ( o.o;o I I 11.87.J I I 17.6Y.~ I I 5.97.) I ( ll.8Y.) I I t 29.47.l
----------------------------------------------------------------------------------------------------------------------------
1 I I
!,!HOLE BllflY/GEHERAL I 1 0 t J I 1 2 I 5
I I 5.97.I ( o.or.1 I ll.8Y.) I 17.67.I I I S.9i0 ( 11.87.1 I t 29.4Y.)
I I I
CHILL- I 1 0 0 l I O O I 1
I ( 5,97.1 ( 0.0iO l o.o:o l 5.9Y.l I l O.0Y.I l O.0Y.l I I 5.97.1
I I I
HEADACHE I O O 2 1 I 1 0 I 2
I ( O.0Y.I I I.OY.I ( 11.8Y.J ( S.9Y.I I I 5.9Y.I t O.0Y.l -I ( ll.87.1
I I I
ILLNESS, NOS I O O O O I O 1 I 1
I t o. 0Y. > l o . 0Y. I t o. 0Y. I t o. ox I I t o . ox I t 5. 97. I I t S. 97. I
I I I
ACHINESS I O O 1 2 I 1 l I 3
I c a.ox, , a.ox, I c s.,r., , 11.a:o I , s.9:o , s.97.1 I I , 17.6Y.I
-----------------------------------1----------l----------l----------t----------l----------l----------l----------l-----------
PERSOtlS WITH Cot1PlAINT!I I 3 I 1 I 2 I 3 I 1 I 3 I I 6
I t 17.6?.I I l 5,9Y.I I l 11.er.1 I c 17.6Y.J I I s.9l.l I t 17.6Y.J I I t 35.3:o
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHs MITH NO COt1PLAINTS I 14 I 16 I 15 I 14 I 16 I 14 I I 11
I, 82.4Y.> Ir M.1:O I, 8&.2Y.1 I c e2.1tr.1 I, 9't.1r.1 I, e2.1t,o I I c 64.77.J
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS MITH NO DATA I O I O I O I O I O I O I I 0
I I o. ax I I r o. o;o I , o. o:o I c o. ox, I r o. ox, I c o. o:o I I c o. o?. 1 0
0
-0
..,
~
Table 2 (Contd)
PATIEtlT COUNT CLINICAL COffl'LAINTS
RECOMBitlAIU HEPATITIS 8 VACCINE
STUDY 01'75
TREAfflENT
LOT HlR18ER CK937
DOSE 40 MCG
PATIENT CUSS NOtlRESPCHJERS (DI
I TOTAL VACCIHEES l 15 PATIENTSI - DOSE t I

1----------------------------------------------------------------------------I
I DAYS POST VACCitlATION I HUt18EI!
CLINICAL 1·- -------------------------------- --- ---- -- ------------------------ ---------- • WITH
COMPLAINTS
,
I O • l • 2 • 3
, • 4
,
I 5 I
,
................................... ..........•..........•.......... .......... .......... ..........•.......... ..........
-----------------------------------1----------l----------l----------l----------•----------•----------l----------•-----------
,
ICOMPLAINTS
srsTEMIC I O • 0 • 0 I 1 • 1 I 2 I I 2
• ( 0.0XI I ( 0.0lO I C 0.0iO I t 6. 7XI • I 6. 7XJ • I ll,3?.I I I I ll.3XI
---------
1
WHOLE BOOT/GENERAL I O I O I O I 1 I O I 1 I I 1
0.0XI • I 0,07.) I( 0.0;.1 I( 6,7XI I( 0,07.I I( 6.77.1 I I I 6.7ll
I I I I I I I
HEADACHE I O I O I O I l • 0 I l I I 1
0.0?.I I I 0.07.1 I ( 0.0XI • I 6.7XI I I 0.01.I I ( 6.7?.J I I ( 6.7XI
I • I I I
DIGESTIVE SYSTEH I O • O I O I O I l I l I I l
o. 01.1 I l o. 01. I I I o. ox I • I o. o:o I c 6. Tl. J I c 6. n 1 • I c 6. 11.1
I I I I I
VONITIHG I o I o I o I O I 1 •I l1 I
I I 0.07.1 I ( 0.07.) I C 0.07.) I I 0.07.1 I I 6.T/.1 I C 6.77.) I I I 6.77.1
-----------------------------------1----------l----------l----------l----------l----------l----------1----------I-----------
PERSotts WITH C0'1PLAINTS I O I O I O I l I 1 I 2 I I 2
I I 0.07.1 I I 0.07.I I I 0.07.) I C 6.7i0 I I 6.77.) I C 13,3)0 I I C U.37.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH HO COttPUIHTS I 15 I 15 I 15 I 14 I 14 I 13 I I 13
I uoo.or.1 I (100,07.1 I U00.07.I I I 93.37.1 I I 93.37.) I I 116.7'!1 I I I 116.7:!I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSOHS 141TH HO DATA I O I O I O I O I O I O I I 0
I I o. oz I I • o. ox, I I o. or. 1 I • •. ox I I I o. ox, I c o. oz I I I I o. o;: 1
0
0
-4)
J::
OD
·-
Table 3
.PATIENT COUNT CLitlICAL COl1PLAlNTS
STUDY 0&75
TREATHEHT
LOT NUHBER 2277k
DOSE 40 MCG
PATIENT CLASS: HOHRESPOHDERS (DI
I TOTAL VACCIHEES C 18 PATIEHTSI - DOSE l I

1----------------------------------------------------------------------------I
CLINICAL 1----------------------------------------------------------------------------I
I I I I I I
MITH
ICOMPLAINTS
...................................
COt1PLAIHTS
,.•••••••••••••••••••• ,.lftl ....... ,•••••••••• ,•••••••••• ,••••••••••••••••••••• ,••••••••••
O l 2 • 3 It 5
I I I I I I I I
REACTION, LOCAL fINJECT. SITEt I O • 1 I O I O I 1 I 1 I I 2
I I 0.07.l • I 6.37.J I C 0.07.l I ( O.o:o I C 6.37.1 I C 6.3Zl I I c 12.57.1
------------
sot1EHESS
.----------------------•----------•----------l----------l----------l----------l----------l----------l-----------
I o I o I o I o • 1 I 1 I I 1
I C 0.07.) • ( 0.07.1 I ( O.OZI I C 0.07.) I C 6.JZI I ( 6.3ZI I IC 6.37.)
I I I I I I I I
ECCHYt10Sl9 I O I 1 I O I O I O I O I I 1
I C O.OZI I I 6.3ZI I ( 0.07.l I I O.OZI I C O.OZI I c O.OZI I I C 6.3ZI
-----------------------------------1----------l----------l----------t----------l----------l----------l----------l-----------
srsTEHIC I 2 I O I 3 I 1 I 2 I 2 • I 5
I ( 12.5Zl I I O.OZI I C 1e.ez1 IC 6.3ZI IC 12.SZI I ( 12.SZI I I C 31.3ZI
-------------------------------------- ·-------------------------------------------------------------------------------------
WHOLE SOOY/GENERAL I 2 0 2 I 0 I 1 I 0 I I
12.SZI I O.OZl I 12.SZI I I O.OZI I I 6.37.1 I c o.o:o I I C 25.0Z l"
I I I I I
FATIGUE/NEAl<HESS I 2 0 1 I 0 0 I 0 I I 2
12.5:o ( o.o:o ( 6.3ZI I ( o.o:o •I C 0 .oz) I C o.oz, I I C 12.SZI
I I I I I
I I I I I
HEADACHE
C
0
o.o:o I
0
o.o:o C
1
6.JZ) •I ( 0
o.o:o I c
1
6.Ji!) I I
0
O.OZI I I C 12.SZI
2
I I I I I
RESPIRATORY 0 0 1 I 0 I 0 I 0 I I 1
C a.oz, C o.o:o C 6.:SZI I C o.o:o I c O.OZI I C o.oz, I I c 6.3ZI
UPPER RESPIRATORY INFECT., NOS 0 0 1 I 0 I 0 I 0 I I 1

( O.OZI C O.OZI ( 6.3ZI I C o.or.1 I c o.or.1 I , o.o:o I I c 6.JZI
I I I I
'1USCULOSKELIETAL 0 0 1 •I l I l I l I I l
C O.OZI ( 0,0ZI ( 6.JZI I f 6.37.1 I c 6. 31.t I I 6.3ZI I I I 6,3ZI
I I I I I
IIHST PAIN 0 0 1 I 1 I l I l I I l
( O.OZI C 0.07.1 ( 6.JX) I ( 6.J;o I c 6. 37.1 I c 6.3ZI I I c 6.31.1
I I I I I
DIGESTIVE SYSTEM 0 0 0 I 0 I 0 I l l
( O.OZI I O.OZI I O,OZI I I o.o;o I c O.OZI I C 6.3:o • • •I I 6.3ZI 0
0
,0
.Ce
.0
Table 3 (Contd)
PATIENT coun CLIHI~AL toffl'LAIHTS
STUDY 0875
TREAT11£HT
LOT tU18ER 22771(
DOSE 40 MCG
PATIENT CUSS: NOtlRESPOHDERS (0 I

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I HUtteER
1----------------------------------------------------------------------------I
CLINICAL
COMPLAINTS • 0
..............................................
I
•
I
, 1
.......... •
I
, 2
.......... ,
•
I
l
.......... ,
I
I
4 I 5 I
.........••..........•..........
I I
,I
WITH
I COMPLAINTS
......... ~
NAUSEA I O I O I O I O I O . I l I I 1
I , o.o:o I c o.oio I c o.oio I I o.o;o I c o.o:o I 1 6.1x1 I I 1 6.3iO
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERsONs WITH tONPUIHTS I t I 1 I 3 I 1 I 3 I 3 I I 6
I I 12.SlO I C 6.3i0 I C 18.&:o I I 6.3)0 I C 18.8:o I C 18.s;o I f I 37.SXI
-----------------------------------1----------1----------I----------I----------I----------I----------I----------I-----------
PERsOHS WITH HO COl1PLAIHTS I 14 I 15 I U I 15 I 13 I 13 I I 10
I I 87.s;o I C93.8)0 I I 81.3?.I I I 93.8i0 I C81.3:0 I I 81.3:0 I I C62.SiO
----------------------
PusOHs MITH No DATA
.------------1----------I----------I----------I----------I----------I----------I----------I-----------
I 2 I 2 I 2 I 2 I 2 I 2 I I 2
I I 11.lY.I I c 11.lXI I C 11.lY.I I I 11.lY.I I I 11.lY.J IC 11.IXJ I I I 11.lXJ
0
0
'°
V,
0
-
Table 3 (Contd)
PATIENT COUHT ClIHI CAl Cot1PlAIHTS
PlASMA-DERlVED HEPATITIS 8 VACCINE
STUDY 0&75
TRE ATI1£NT
LOT Hl.t18ER 2Z77K
DOSE 40 MCG
PATIENT CLASS NOHRESPONDERS ID)
I TOTAL VACCJNEES I 17 PATIENTS) - DOSE 2 I

1----------------------------------------------------------------------------I
l----------------------------------------------------------------------------1
CLINIC AL
COtPLAlllTS
................................... I
, O I 1
..........•.......... • 2
,
.......... I 3
, I "
..........•....•..... I 5
.......... I
, ,
WI TH
.......... ICottPUI
-----------------------------------•----------•----------l----------•----------•----------1----------1----------1-----------
.........,
HTS
.
svsTEHtt I o I 1 • o I o • o I o I I 1
• 1 o.o;o • r 6.no • 1 o.o;o I I o.o;o • r o.o;o I I o.ox, I I 1 6.n,
----------------------------------------------------------------------------------------------------------------------------
• I I • I I I I
HUSCULOSl<ELIETA L I o I l I O I O I o I· o I I l
I I 0.0lO 11 6.71.1 . I Cl.OX! . I O.OXl. I O.OXl I I o. o:o I I I 6.7Xl
I I I I I I I I
ttUSClE STI FFNESS I O I l I D I O I O I O I • l
I ( O.OY.I I C 6. T/.1 I I O. OXI I I 0.0:1.1 I C O.OXI I I o. o:o • I I 6. 7%1
-----------------------------------1----------•----------l----------l----------1----------1----------•----------I-----------
PERSONs WITH tOttPUINTS I o • 1 I o I o I o I o • I 1
I , o. ox , 1 c , •1x I I , o. ox , I I o. o;o I , o. ox, • , o. ox , • I , • •n ,
----------------------------------- 1----------I----------I---------- I---------- I---------- I---------- I---------- I-----------
PERSONs WITH HO COtff'U I HTS I 15 • 14 I 15 I 15 I 15 I 15 • I 14
I 1100.0XI • I 93 . 3Xt I 1100.tXl I 1100.0XI I 1100.0XI I 1100.0XI I I I 93.lXI
-----------------------------------1---------- l---------- l---------- •----------I---------- I---------- I---------- I-----------
PERSONS WITH HO DATA I 2 I 2 • 2 • t I t I 2 , I I 2
I I 11.0:0 I I u.ex, • I U .6XI I I u .ex, • I 11.6%) • I 11. 0Y.l I • I 11 .8)0
0
0
,D
-
IJ1
-
Table 4
PATIENT COUNT HAXlltUl1 TEHPER ATURES
RECOteINAHT HEPATITIS 8 VACCINE
STUD Y 0875
TRE ATN£NT
LOT tfJHB(R I CK9l7
DOSE 1 40 MCG
PATIENT CLASS: NCIHR[SPONDERS IDl
I TOTAL VACCIHEES I 17 PATIENTS) - DOSE l •
Il---------·-----------------------------------------------------------------------------1
DAYS POST VACCINATIOff I tfJr18ER
nAX TEMPERATURE
( DE6 F, Olll ll
l---------------------------------------------------------------------------------------1
I O I 1 I 2 I l I 'I I 5 I I
WITH
I MAX TEMP
••••••••••••••••••••••••••••••••••• l•••••••••••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
HOl!ltAL I 1 I 1 I l I l l I 2 I I l
s.,;o I t 5 . 91.I • t S.9iO I I 6.liO •I I 5,9l!I I I 12 . SXJ I • I 5 .9iO
I I I I I
< 99 10 I 12 I •
ll I 11 •
I 10 I 12 I I 6
I• I 58.81.1 I ( 70.6)0 I I 76.51. l I I 68.&iO I I 58.&lO I ( 75.0iO I I I 15.ll! )
I I I I I I I I
99 - 99 .9 I 5 I
29.'tlO I
it I 2 I I 5
• I 1
l n.51.1 I I 11.8?.I I I 25.0iO I f 29.4lO I l 6.3?.J I
I I 7
I I '11.21.1
I I I I I I I
100 - 100 .9 I 1 I 0 I 0 I 0 I 0 I 1 I I 2
5.91.l I I 0 . 01.1 I c 0.01., I f O.0iO I I o.or., I c 6. 1r.1 I I I 11 .8)0
102 - 102.9 I o I o I 1 • o • l I o I I 1
I f 0.0)0 I I 0 . 0)!1 I I 5.9)!) • ( 0.0iO I ( 5.9)0 I I O.0l!J I I ( 5.9?.J
------------------------1----------l----------l----------l----------
TDIPt RATUR£ Tllk[N I 17 I 17 I 17 I 16
l----------l----------1
I 17 I 16 I
--------------------- II-----------
l7
I (100.01.) I 1100.0iO I 1100 . 0l! I I ( 94.ll! I I 1100.0)!1 I I 94.lY.J I I 1100.0i! )
------------------------1----------1----------l----------
1£1tPERATURE NOT TA~EH I O I O I O
l----------t----------l----------l---------------------
I l I O I 1 I
l-----------
I 0
I ( 0. 0l! I I I O. 0l! ) I I O. 0)! l I ( 5 . 9% I I ( 0 . 0)! J I I 5. 9)0 I I I O. 0l! I
0
0
,0
lJ'I
N
·-
Table 4 (Contd)
PATIENT COUNT NAXIl1Ut1 TENPERATURES
RECOl'IBINAHT HEPATITIS B VACCINE
511Jl)T I 08 75
T1'EATl1£NT
LOT Nllt18ER : 0<.937
OOSE : 40 MCG
PATIENT cu ss: NONRESPONl>ERS CDJ
I TOTAl YACCINEES C lS PATI ENTS) - DOSE 2 I

•---------------------·
I -----------------------------------------------------------------•
DAYS POST VACCINATION I NUMBER
NAX TENPER Al\JRE
IDE& F, ORALI
1
I ---------------------------------·
O I 1 I 2 I -----------------------------------------------------•
3 I 4 I 5 I I • HAWint
X TENP
••••••••••••••••••••••••••••••••••••••••••••••••..••••••••••••••••••l••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
NORNAL 2 I 2 I 2 I z z 2 I I 2
14.37. 1 I c n.37.1 I c n.1;0 I 1 14.37.I • • c 1s.4;:1 I• c 14.37.1 • I t 13.3lO
I I I I I I I
< ,, 9 I
10 I 9 I 10 I 10 I 10 I I 7
64.3¼). ( 66.7)0 I I 60.o;n I I 71.4)0 I ( 76 . 97.) I C 71. 41. ) . I I 46 . 71.l
I I I I I I I
99 - 99.9 l I 3 I 4 I l I l I 2 I I 5
21. 47.1 I C 20. 07. I I C 26 . 71.) I C 7.17. 1 I 1 7.77.1 I c 14.37.1 I I I 33 .37.1
100 - 100.9 I o I o I o I l I o • o ·I I l
• C 0 . 07. 1 I ( 0.07.I I C 1 .07. ) I I 7.17.) I C D.07.) I C 0.07.) • I C 6.77.)
------------------------1----------1----------l----------
TENPERATURE TAKEN I 14 I 15 I 15
l----------l----------•----------•---------------------•-----------
I 14 I U I 14 I I lS
I 1 93_3;0 t 1100.0;:1 I uoo.o;o I c 93.37.1 • t M . 7;o I c 93.37.1 I I n oo.o;:,
------------------------1----------1----------l----------l----------•----------•----------•---------------------I-----------
TEMPERATURE HOT TAKEN I 1 • 0 I O I 1 • 2 I 1 • • 0
I c 6 • 1x 1 • 1 o. o;o I c o. o;: 1 I c 6. 77. 1 • c u . 1;: , • c 6 . 77., I I c o. oz 1
0
0
-0
1.11
vf
Table 5
PATIENT COUNT t;~XIl1UN TENPERATURES
PLAStll-DERIVED HEPAlITIS B VACCINE
STUI)'( 0875
TREATttENl
LOT NUt1eER 2277K
DOSE
PATIENT CLASS ~~f~ERS IOI
----------------------------------------------------------------------------------------------------------------------------
l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I tlUMBER
"AX TENPERATUllE
IDEG F, ORAL)
l--------------------~------------------------------------------------------------------1
I 0 I 1 I 2 I 3 I 4 I 5 I I I HAXMITH
TEt1P
••••••••••••••••••••••••••••••••••••••••••••••l••-••••••l••••••••••l•••••••••••••••••••••l•••••u•••l•••o•••••I••••••••••
HOllt1AL I 2 I 2 I 2 I 2 I 2 I 2 I I 2
I l 12.51.1 II 13.]1.) I l 12.51.1 I I 13,l:t.l I I 13.3:t.l I I 13.31.1 I I I 12.5%'.I
< 99
I
I 13
I
I 7
I
I 9
I
I e
I
I , I
I 8
I
I
I
I !S
Il 81.37.1 II 46,71.J I l 56.31.t I I 53.3:iO I I 60.0:t.l I I s1.11.1 I I I 31. 3%'.I
I I I I I I I I
99 - 99.9 I l I 5 I 3 I 4 I l I l I I 5
II ' 6.3,0 II 33.31.) I ( 18.8i0 I I 26. Tl.I I I 20.0iO I l 20.07.I I I I 31.liO
I I I I I I I
100 - 100.9 I 0 I l I 2 I l I 1 I 1 I I l
0.01., II 6. 71.) I I u.s::o I I 6.71.J I I 6. 77.1 I 1 6.7l0 I I I 18.BiO
102 - 102.9 I o I o I o I o I o I l I I l
I r O. 07. J I ( 0. or. J I I O. 07. J I I O. or. J I l O. or. I I ( 6. 77.1 I I I 6. 3;0
-----------·- ------------I----------I----------I----------I----------I----------I----------I---------------------I-----------
TEt1PERATURE TAKEN I 16 I 15 I 16 I 15 I 15 I 15 I I 16
I I 88.'1'/.I I I 83.31.) I I 88.9Z) I I 83.]7.J I I 83.]ZI I I 83.31.1 I I I ee.,z,
------------------------1----------I----------I ---------- I---------- I---------- I----------I---------------------I-----------
TEl1PERAT\JIIE NOT TAKEN I 2 I 3 I 2 I 3 I l I l I I Z
I I 11.lZl I< 16.7Zl I I 11.11.1 11 16.7l0 If 16.71.1 I I 16.71.1 I I I 11.liO
0
0
-0
V,
- ~
Table 5 (Contd)
PATIENT COUil' HAXIHU1 TEHPERATUAES
PLASHA-DERIVED HEPATITIS 8 VACCINE
STUDY 0875
TREATl1ENT
LOT NUt18ER 22771(
DOSE 40 MCG
PATIENT CLASS HOHRESPCIM)ERS 1D1
I TOTAL VACCIHEES I 17 PATIEHTSI - DOSE 2 •

•---------------------------------------------------------------------------------------1
I° DAYS POST VACCINATION • HUt18ER
HAX TEMPERATURE
(DEG F, MALI
•---•-----------------------------------------------------------------------------------1
I O I l I Z I J I 4 • 5 I I • MAXWITH
TEHP
······························••1111••·······················································································
NORMAL 1 I 1 1 1 I 1 I 1 1
• 6.71.l
I• ( 6.7:iO I ( 6.11., I, I• I 7.'11.J I I 7.llO I I 1. 11.1 I• I• I 6. 71. I
I I I I I I
< .,, I 9 I• 10 I 9 I, 10 I• e I 10 I I 6
I I 60,0Y.l I I 66.77.1 I I ,o.o:o I I 71.ttY.I I I 57.lY.I I I 76.97.1 I I I 40.DiO
I I I I I I I I
99.9 I I 3 I 4 I t I 2 I I 7
99 -
" 5
l 1 26.T/.J I I 20.07.l I I 26.T/.J • I 14.JiO •I I 3S.7i0 I ( 15.41.l I I 1 46.77.1
I I I I I I I
1oz - I I I I I I•
102., 1 I
6.T/.l IC
0
0.01.1 I ,
0
o.or., I ,
0 0
' 0
0.07.l I I 0.OiO I ( 0.0iO I I I
0
o.o;o
101 - 101., I o • l I l I 1 I o I o I I 1
I, o.o;o I t 6.11.1 I , ,.r1.1 I 1 1.11., I , o.o;o I I o.o;o I • , ,.1;0
------------------------1----------1----------I----------I----------I------·
TEHPERATURE TAKEN I 15 I 15 I 15 I 14 • 14
---l----------1---------------------1-----------
I 13 I I 15
I I es.21.1 I 1 89.27.1 I c 88.27.J I I 82.47.J I c 92.47.1 I I 76.57.1 I I I e&.Z7.l
· TEMPERATURE
------------------------1----------1----------l----------l----------l----------l----------l---------------------l-----------
NOT TAKEN I 2 I 2 I 2 I :S I J I 4 I I 2
I I 11.a;o I f 11.ar.1 I I 11.e:o I I 17.6i0 I f 17.6)(1 I I n.s;o I I I 11.8%1
0
0
.0
IJ'I
- IJ'I
PREIMMUNE ADULTS
OOQS6
PREI~MUNE ADULTS - POPULATION Slfflll1ARY
Pre111111une adults are included in the populations of two studies (Study 817 and
Study 813, addendum 6 and 7). The pre-exist;ng hepat;tis 8 antibody in this
population may be naturally acquired or due to previous administration of
either plasma-derived or yeast recOfllbinant hepatitis 8 vaccine. The studies
are designed to assess antibody and clinical responses of preinmune adults to
a single 10 or 5 mcg booster injection of hepatitis 8 yeast recolllb1nant
vaccine.
To date, 63 preinnune adults have received a 10 11eg dose of yeast recOlllbinant
vaccine. Anti-HBs responses 1-2 months after the booster injections have been
measured 1n ~IU/~1 for 31 subjects. All 31 participants de1110nstrated a boost
in ant1-H8s titer at that time. The Giff at 1-2 1110nths post-vaccination was
1110.6 mlU/ml versus a prevaccination GMT of 62.0 mIU/ml. Ant1-H8s responses
expressed in S/~ ratio units are also available for an additional 31 subjects
whose antibody response was measured 2-4 weeks after a single 10 mcg booster
injection. Ninety-seven percent (30/31) of these participants de1110nstrated a
boost in antibody titer at 2-4 weeks. One vaccinee who was seronegathe at
the time of vaccination but antibody positive at an earlier t1me failed to
develop detectable antibody four weeks after vaccination.
Twenty-eight preinnune adults have received a single 5 mcg booster injection
of vaccine. All 25 participants tested at 1-2 months after the booster
injection demonstrated a boost 1n ant1-H8s titer. The GMT 1-2 months
post-vaccination was 1275.2 mIU/ml versus a pre-vaccination GMT of 59.9 mIU/ml.
The vaccine has been well tolerated in this population. No serious reactions
attributable to vacc1nat1on have been reported.
31701/1
1 /11 /86
00957
PREIMMUNE ADULTS
Study 813 - New Yort, NY - Dr. M. Davidson

The population for · study 811 addenda 6 and 7 consists of two groups of
pre-innune health care personnel. Group l (addendum 6) includes personnel who
received plasma-derived hepatitis B vaccine at 0, 1, 2, and 9 tno[lths, 5 to 7
years previously. These subjects receive a 10 mcg booster injection of yeast
recombinant hepatlth 8 vaccine lot C-11126. Group 2 (addendum 7) includes
subjects who previously received 2.5 mcg injections of yeast recombinant
vaccine at 0, 1, and 6 months in study 813. These participants receive either
a 5 mcg or 10 mcg booster injection of yeast recombinant vaccine lot C-fi126.
Thirty-one ·group l participants have received a lO mcg injection of vaccine.
At one 1110nth post the booster injection, 21 of 30 (70%) subjects had a greater
than four-fold rise 1n ant1-HBs titer.
In group 2, 28 participants have received a 5 mcg injection and 28 have
received a 10 mcg injection of vaccine. At 1-2 months after receipt of the
booster injection, 21 of 25 (841) subjects, who received a 5 111eg dose, had a
greater than four-fold rise in anti-HBs titer. The GMT for all vaccinees was
59.9 mIU/ml pr1or to the booster dose and 1275.2 mlU/ml 1-2 1110nths post the
booster 1nject1on.
Twenty-three of 27 (85%) participants, who received a 10 11eg booster dose, had
a greater than four-fold rise in antt-HBs titer 1-2 months post the vaccine
injection. Prior to the booster injection, the GMT for all vacc1nees was 96.5
mIU/ml. The GMT rose to 1337.0 mIU/ml 1-2 months after the booster dose.
Refer to the sullllWlry on health care personnel/healthy adults for data
regarding other subjects vaccinated in this study.
Study 817 - West Point , PA - Dr. R. Bishop

The study population consists of 2 groups of healthy adults. Group l includes
pre-innune adults (naturally acquired anti-HBs or pl1s1111-dertved vaccine
induced) who receive a single 10 incg dose of yeast recOllbinant vaccine lot
c-K444. Group 2 includes healthy adults who were nonresponders to previously
adm1n1stered plas111-der1ved vaccine. These participants receive a 10 mcg
injection of yeast recOlllbinant hepatitis B vaccine lot C-K444 at 0, 1, and 6
months.
Five healthy pre-t nnune adults (group 1) have received a 10 mcg injection of
vaccine. All five subjects showed a greater than four-fold rise in anti-H8s
titer three months post the booster injection. The GMT for all the vaccinees
prior to the booster dose was 5. 7 mIU/ml. At three months after the booster
injection , the Gf.1T for all vaccinees was 402.5 mlU/ml. \
31411/1
l /8/86
Study 817 - West Point , PA - Dr. R. Bishop (Cont.)
There were no serious or alaming adverse experiences attributable to
vaccine. Refer to the summary on non-responders/hyporesponders for data
regarding other subjects vaccinated in this study.
31 411/2
l/8/86
Study 81J
00959

Study 813

dose levels of yeast recombinant hepatitis 8 vaccine
among the following populations:
1. Health Care Personnel (Seronegative)
2. Preimmune Adults

Lot 81954I/18071/C-l220 {10 mcg HBsAg/0.5 ml)
Lot 85860/22123/C-14125 (20 mcg HBsAg/ml)
lot 85861/22124/C-'4126 (10 mcg HBsAg/ml)
PRINCIPAL Morton Davidson, M.D.

INVESTIGATOR: New York Univers1ty Medical Center
Onlversity Hospital
560 First Avenue
New York, NY 10016
SECONDARY Saul Krugman, M.O.

INVESTIGATOR: Professor
Department of Pediatrics
550 First Avenue
New York, NY 10016
SlUDY LOCATION: New York University Medical Center

University Hospital
560 First Avenue
New York, NY 10016
DATE C0'4PLETED: In progr..ess.
23401/1
l /18/Bf> •
Study 813
STUDY POPULATIONS: Under the original protocol and subsequent addenda,

the following groups of health care personnel are
included in the study. Participants may be of either
sex, but pregnant women are excluded. Initially
seronegative subjects have not previously received any
ndiBn No. Characterist Ics liluliber Vaccine Lot No.C Regimen
Initially 50 972/C-IC444 1011ttg (1.0 111) at

seTOne91t ive 0, 1, and 6 IIDl'lths
Initially so 972/C-IC444 5 mc:g (0.5 •I) at

seronegative 0, l, and 6 IIDl'lths
Initially so 972/C-IC'4' 2.S 11:9 (0.25 •1) at

ceronegativo 0, 1, and 6 inonths
Initially 50 819S'I/1807 I/ 10 mcg (0.5 ■1) at

seronegative C-L220 O, 1, and 6 n,nths
Initially so 819S'I/ 18071/ S IIIC9 (0.25 111) at

seronegative C-L220 0, 1, and 6 mnths
Initially 50 858&0/22123/ 20 IICg (1.0 111) at

seronegative; ~125 0, 1, and 6 110nths
~ years of age
Initially so 85861/22124/ 10 mcg (1 .0 111) at

seronegative; C~l26 0, 1, and 6 11>nt.hs
~40 years of age
Vaccinated 3-S yrs 100 85861/22124/ 10 mcg (1.0 111) at

previously with C~l26 tiire 0
plasma derived
hepatitis B vaccine
(IEPTAVAX-8)
• 111 Vaccinated pre- 50 85861/22124/ S n:g (0.5 1111) ~

viously with C~126 10 IICg (1.0 111) at
three 2.5 nicg tin o
doses of recanbi-
nant vaccine under
Add. 112.
23401-2
1/18/86
00~61
Study 813

STUDY POPULATIONS. Those enrol led under addendum #5
who fail to develop antibody following 3 injections of
vaccine or have only a transient response that becomes
negative by 12 months after the first dose may receive
a fourth injection of vaccine.
Participants will be asked to record their temperature
for 5 days after each injection of vaccine and to note
any local or systemic complaints. Unexpected or
serious reactions are to be reported immediately to
the study physician.
Blood samples will be obtained from the initially
seronegative groups prior to and on the day of the
first vaccination. Follow-up samples w111 be obtained
1, 2, 3, 6, 8, 12 and 24 months after the initial
injection of vaccine {initial protocol and addenda
#1-5). Follow-up samples from persons vaccinated
under addendum #6 are only taken 1 month after
vaccination while persons enrol led under addendum #7
have blood samples taken 2 weeks, 4 weeks, and 6
months after vaccination.
Blood samples will be assayed for HBsAg, anti-HBc,
anti-HBs and ALT by Or. Krugman I s laboratory and may
be assayed for yeast antibody by the Merck Sharp and
Oohrne Research Laboratories. Samples with an anti-HBs
titer >25 mIU/ml may be tested to determine the
relative proportions of anti-! and anti-~ activity.
RESULTS: PREIMHUNE ADULTS (Previously Vaccinated

with plasma-derived hepatitis B vaccine):
10 mcg lot 85861/22124/C-f.1126 at time O
1. Number Vaccinated: 31
At one month following administration of the
booster injection of yeast recombinant vaccine, 21
of 30 (70%) participants had a greater than 4-fold
rise in anti-HBs titer.
23401-13
1 /13/86
00962
Study 813
RESULTS: (Contd) Refer to Table l for ant1-HBs titers prior to and

post the booster injection.
participants after the booster injection of
vaccine. The overall frequencies of complaints
are presented below:
Frequency in%
Injection Site 32 (6/19)
Systemic 21 ( 4/19)
Refer to Table 4 for listing of specific

complaints. Temperature data are provided in
lable 5.
No serious or alanning reactions attributable to
vaccine have been reported.
PREIMMUNE ADULTS (Previously Vaccinated

with Yeast Recombinant Hepatitis 8 Vaccine:
5 mcg lot 85861/22124/C-Ml26 at time O
10 mcg lot 85861/22124/C-14126 at time 0
Dose Level
5 mcg 28
10 mcg 28
who received a 5 mcg injection of vaccine and -27
participants who received a 10 mcg injection.
23401-14
1/13/86
Study 813
RESULTS: (Contd) At 1-2 months after administration of the booster

injection, 21 of 25 (84%) participants who received
a 5 mcg dose had a greater than 4-fold rise in
anti-HBs titer. The G~T for all vacc1nees was 59.9
mIU/ml prior to receipt of the booster 1nject1on and
1275.2 mIU/ml 1-2 months after the booster dose.
Refer to Table 2 for a listing of anti-HBs titers
prior to and post the booster injection.
Twenty-three of 27 (85%) participants who received a
10 mcg booster dose of vaccine, had a greater than
4-fold rise in anti-HBs titer at 1-2 months post the
injection. The GMT for all vacc1nees was 96.5
mIU/ml prior to receipt of the booster injection and
1337.0 mIU/ml 1-2 months after the booster dose.
Refer to Table 3 for a listing of anti-HBs titers
prior to and post the booster injection.
participants who received a 5 mcg injection and 14
participants who received a 10 mcg injec.tion of
vaccine. The overall frequencies of complaints are
presented below:
Type of Complaint Dose Level Frequency in%

Injection site 5 mcg 40 (4/10)
Systemic 10 (1/10)
Injection site 10 mcg 21 (3/14)
Systemic 0 (0/14)
Refer to Table r, for a listing of specific clinical

complaints by dose level. Maximum temperature data are
provided in Table 1.
23401-15
1/13/86
Study 813
PUBLICATIONS: Davidson~. Krugman S. Immunogenicity of recombinant

yeast hepat1t1s 8 vaccine. Lancet 1985; l :108-9.
Davidson~. Krugman S. Recol'lb1nant yeast hepatitis 8
vaccine: Side effects and 1nanunogenic1ty compared
w1th plasma-derived hepatitis B vaccine. Submitted
for publicatton to Hepatitis Scientific Memoranda.
23401-6
1/13/86
Table 1
Anti-HBs Response Following Primary I11111unization with
Plasma-Derived Hepatitis B Vaccine* and a
Subsequent Booster Dose (10 mcg) of
Yeast Recombinant Hepatitis B Vaccine**
5 to 7 Years Later
Anti-HBs Res~onse SlN

No. Age Sex Years After Initial l nnun1zat1on Weeks after Booster
...J_ ..i... _6_ ...L _2_ ...L
o) {6)
51 M 69 <2.1 101 101
45 F 72 <2.1 22 12
37 F 3.2 <2. 1 5 6.5
36 M 26 <2 .1 165 115
28 M 27 <2.1 22 16
74 H 23 <2.1 <2 .1 <2 .1
47 M 93 2.3 82 95
54 M 34 2.6 226 165
44 M 103 4 165 78
59 H 24 4 60 33
39 fll 40 6 40 28
64 F 160 9 179 179
46 F 73 9 225 158
49 M 145 12 l 57 99
41 F 177 13 192 183
45 F 144 18 205 250
74 F 214 20 177 238
49 F 205 38 288 209
43 F 100 41 168 145
31 F 64 49 146 173
34 M 206 87 154 151
35 M 266 192 195 144
52 F 128 2.8 106 83
41 M 10 <2.1 14 88
34 H 8 13 118 120
30 M 125 22 112
35 M 1£>8 36 190 203
33 F 217 66 147 167
28 F 28 3.4 112 153
34 M 101 29 138 98
34 H 204 112 173 160
* Plasma-derived vaccine: Lot· #C-E575 , 20 mcg dose at 0, 1, 2, and 9 months.
** Yeast recombinant vaccine: Lot #C -f:1126, 10 mcg dose.
23401-16
1/13/86
00966
Table 2
Antibody Responses to a 5 mcg Booster Injection of

Yeast Recombinant Hepatitis B Vacc1ne Lot C--M126 1n
Health Care Personnel Who Previously Received 2.5 mcg Injections
of Yeast Recomb1nant Vacc1ne at 0, 1, and 6 Months
Anti-HBs Titer in mIU/ml

1-2 Nonths
Case I. Prior to Booster Injection Afttr ~ooster Injection
b) (6J 142 9275
115 2473
157 944
33 2145
5.5' 153
318 4140
Neg. 218
13 940
19 832
6.9 244
25 274
7.6 301
489 811
* 20 1100
70 1662
59 228
241 3645
90 6360
551 7278
19 1553
3390 4116
23 277
lr1r1r 1559 2876
394 5192
45 2865
GMT 1n mIU/ml 59.9 1275.2
* Subject was antibody positive at an earlier time.

~• Titer determined 4 months after booster injection.
*** Titer determined 3 months after booster injection.
23401-17
1/13/86
Table 3
Antibody Responses to a 10 mcg Booster Injection of
Yeast Recombinant Hepatitis B Vaccine Lot C-M126 in
Health Care Personnel Who Previously Received 2.5 mcg Injections
of Yeast Recombinant Vaccine at 0, 1, and 6 ~onths
Ant1-HBs Titer in mIU/ml

1-2 Months
Case# Prior to Booster Injection After Booster Injection
(6) (6) 73 800
812 5828
150 651
115 953
55 3732
3.6 18
358 215
1778 574
86 2789
94 2543
7 1635
231 3837
128 2410
104 3136
212 9161
288 490
Neg. 245
15 169
2498 1837
95 5/16
84 1784
56 6188
300 1611
759 4514
93 3508
18 606
145 948
GMT in mIU/ml 96.5 1337.0
* Subject was antibody positive at an earlier time.
23401-18
1/13/86
Table 4
PATIENT COUHT ClIIUCAL CDMPUJHTS
R[Cot18Jt1ANT HEPATITIS B V~CCIHE
STUDY 0813
TRE ATMENT
LOT NUt'BER CNIZ6
OOSE 10 ttCG
PATIENT CLASS: PRElrt'IUHE ADULTS (Previously vaccinated with plasma-derived hepatitis B vaccine)
I TOTAL VACCJNEES ( 21 PATIENTS)· DOSE 1 I

1----------------------------------------------------------------------------I
• DAYS POST VACCINATION • NU11BER
1 ----------------------------------------------------------------------------•
CLINICAL
COMPLAINTS f
I
O •
I
1 I
, I
2 •
I
3
, • 4 • 5 •
I
WI TH
.COMPLAINTS
...................................•.......... .......... .....•....•.....•....•..........•..........•.......... ..........
I I
,
I
REACTI<»f, LOCAL (INJECT. SITE) I 3 I Z f 2 I 0 I 0 I O I I 6
t , 1s.s:o I t 10.5:o I 1 10.s:o I t o.0Y.l • t 0.07., I , o.o;o t I t 3l.6;o
-----------------------------------1----------l----------l----------l----------l----------l----------
soRrnEss I 3 I 2 • 2 I O I O I O
t----------
I
l-----------
• 6
I t 1s.sr., I , 10.s:o I , 10.s:o I 1 0.01-1 t , 0.07., I , 0.01-1 • I , 31.6:o
I • I I I I • I
STIFFNESS/TIGHTHESS I l I O I O • 0 I O I O I I 1
I ( 5.37.) f ( o.o:o I I o.o:o I I o.o;o I I 0.0Y.) • C 0.0iO I • I 5.37.1
-----------------------------------
svsnN1c
l----------t----------l----------l----------t----------•----------l----------
I 1 • 4 I 2 • 2 • 3 I 2 I
•-----------
I <t
• t 5.37.l • I 21.17.1 I I 10.57.) • t 10.57.l I I 15.8XI I l IO . SY.I I I I 21.lY.I
14fOLE BOOT/GENERAL I 1 2 2 2 1 1 2
S.37.I I 10.57.1 I 10.SY.) ( 10.57.) f S.37.J f 5 . 3)0 , 10.sx,
FLUSH I 1 0 l 0 0 0 l
5.3)0 ( o.o;o ( 5.3XI ( o.o:o ( 0.07.) ( o.o:n I S .JY.I
FAT IGUE/WE AKNESS I 1 1 l 1 0 0 2

5.37.t ( 5.37.t C 5.3)0 C 5.37.1 I 0. 07.) ( 0 . 07.1 C 10 . 5:1. I
NALAI SE 1 1 1 0 0 0 2
( 5.37. 1 I 5 .3lO I 5.37.t ( o.o;o I 0 .117. t ( 0.07.t I 10.SiO
HEADACHE 0 1 0 0 0 0 1
I 0 . 117.) ( 5.37.t ( 0.07.1 ( o.o;n ( 0. 07. J C 0.0lO I 5. 37.J
ACHINESS 0 1 0 l l l l
( 0.07.) C 5.37.I ( 0.07.1 ( 5.3i'.I C 5.3)0 ( S.3i'.J ( 5.3i'.J
INTEGUNENTART SYSTEH 0 0 0 0 1 0 1
( 0 . 07. ) C o.o:o ( o.o:o ( 0.0)0 ( s.1;0 I 0.0i'.t I S. li'.t
RASH , HOS 0 0 0 0 1 0 1
o.o:o ( o.o:o ( 0.0Y.I ( 0.0i'.I I 5. 3Y.I C 0.0i'.I I 5.li!t 0
0
.0
c,,
O!t
•
Table 4 (cont)
RECOM&JNAHT HEPATITIS B VACClll(
STUDY 0813
TREATf'IEHT
LOT HUtl8ER CM1Z6
DOS£ 10 t1CG
PATIENT CUSS: F'REitfllJHE ADULTS
I TOTAL VACCINEES f Zl PATIENTS> - DOSE I I

Il----------------------------------------------------------------------------1
DAYS POST VACCINATION INUMBER
CLINICAL 1----------------------------------------------------------------------------I WITH
COttPLAINTS I O I 1 I 2 I 3 I 4 I 5 I IC011PLAJNTS
•••••••••••••••••••••••••••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••1••••••••••
I I
CARDIOVASCULAR I O I 1 I O I O O O l
o. oio I c s. 3?., I I o. o;o I • o. or.> « o. or., 1 o. or., 1 5. 3r.,
I I I
ARRHYTHMIA, O'ftlER I O I 1 I O I 0 0 0 l
o.or.1 I l s.3?.J I I o.or., I c o.or., • c o.or., c o.o;o , s.3?.I
I I I
11U5CUL0SKELETAL I O I 1 I O I 1 1 1 2
0.01.I I I 5.3?.I I I o.o;o I I 5.3?.I I 5.3)0 I 5.3?.I ( 10.SiO
I
ARTHRALGIA COTHERJ I 0 I 0 0 I 1 1 1 1
O. ox J I f O. o:o ( 0. 01. > I C S. 3?. I l 5. 3?. > l 5. 3:t. > ( 5. 3:t. >
I I
ttfALGIA I O I l O I O O D 1
c 0.01., I 1 5.3XJ I o.ox, I c o.oY.t c o.o;o c 0.0:t.1 c 5.31.t
I
DIGESTIVE SYSTEM I O I O O I l l l 2
o.o;o I I o.o;o I 0.OY.J I C 5.liO I 5.liO I 5.3Y.I C 10.51.)
I
NAUSEA I 0 I 0 0 I 1 l l 2
o.o;o I I o.o::o I o.o::o I C 5.3:t.l I S.3Y.I C 5.3Y.I ( 10.SY.I
I I
ORGANS OF SPECIAL SENSE I 0 I O 1 I O O O 1
o.o;o I c o.o;o , s.31.J I • o.or.1 1 o.or.> c o.or.1 1 s.31.1
I
COHJUHCTIVITIS I O Io I 1 I O O O l
I c o.or.> I c o.or., I c s.31.1 I c o.o::o c 0.0,:1 c o.o;o , s. 3;0
-----------------------------------1----------l----------1----------1----------t----------l----------l----------l-----------
PERsoHs WITH C0ttPLAIHTS I 4 I 5 I 4 I 2 I 3 I t I I 8
I I u.uo I • 26.3iO I c 21.1r.1 I c 10.sr.1 I 1 1s.e;.o I , 10.sr.1 I I c 42.1::0
-----------------------------------I----------I----------I----------I----------I----------I----------I----------I-----------
PERSOt1s WITH NO C0HPUIHTS I 15 I 14 I 15 I 17 I 16 I 17 I I 11
I l 78.9?.J J l 73.77.J J l 78.9?.I I ( 89.SXI I I 84.ZY.J I C 89,SX) I I ( 57.9Y.I
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH NO DATA I O I O I O I O I O I O I I 0
I , o.or., I , o.or., I c o.or.1 I c o.or.1 I c o.or.1 I c o.or.1 I I , o.or.1
0
0
"'
:,..
"'
-
Table 5
PATIENT COUNT HAXIKJl'I TEMPERATURES
RECOt'BINANT HEPATITIS 8 VACCitlf
STUOY 0913
TREATMENT
LOT NIJlfflER Cttl:?6
DOSE 10 HCG
PATIENT CUSS PREit,Uff: ADULTS
I TOTAL VAttIHEES f 21 PATIEHTSI - DOSE 1 I

l---------------------------------------------------------------------------------------1
I DAYS POST VACCINATION I NUM8ER
MAX TEMPERAT~ 1--------------------•····-····•·•····•·•••·-·-·-•··········-···-···-··--··-------··----I MITH -
I DEG f, ORAL)
t!ORHAL
I
I
O
B
42.UO
I
..1
•
I 2
B I
I 3
B •
I It
B
•
. I
•
5
9
•
I 11
I
I
I C 4<t.<t1.) I C 42.17.) I ( 42.11.1 I ( 47.41.1 -, I 57.91.) I
• HAX TEHP
························•······· ···························-················•··········•··········•·····················
I
I IS
I I 42.lX)
I
< 99 I 9 I B • 9 I 10 • 9 I B I I 7
47.<t7.) I t lt<t.41.) • I 47.47.) I t 52.6)0 I t 47.ltZl I I lt2.l1.l • · I c 36.157.J
I I I I I
99 - 99.9 I z • 1 I l I o • l I o I I 3
10.57.) I { 5.6iO I t 5.37.) I C 0.01.1 I C 5.31.1 I t o.o;o • • C 15.87.1
I I 1 I I I I
100 - 100.9 I o I 1 I 1 I 1 I o I o I • l
I c 0.01.J • t 5.67.1 I c 5.31.J I t 5.3iO I c 0.01.1 I c 0.01.1 • • c S.31.1
--·---------·--------·--1--·-····--1--··---·-·•·--·-···-·•·-··--····1--····-··-•····-··--·•-------·---·----·----•·----------
TEMPERATURE TAKEN I 19 I 18 I 19 • 19 f 19 I 19 I • 19
I c 90. 5lO I t 85. 71. I I c 90. 57. I I c 90. 57. I I c 911 • 57. I I c 911 • 51.1 I I c 90. 51. I
-----------------------1-·-------·1----------l----------l----------l----------t----------1---------------------1-----------
TEMPERATURE NOT TAKEN I 2 I 3 I 2 I 2 I 2 I 2 I I 2
I c 9.57.1 I c -1<t.37.I I C 9.51.1 I C 9.51.1 I C 9.51.1 I C 9.5iO I • I 9.5XI
0
0
,0
....,,
0
,
Table 6
PATIENT COUNT CLINIC AL Cot1PLAINTS
RECOMBIHANT HEPATITIS B VACCINE
STUDY 08ll
TRE ATMENT
lOT tMfflER Ctll26
DOSE 5 t1CG
PATlEHT CLASS PREIMMUNE ADULTS (Previously vaccinated with yeast recombinant hepatitis B vaccine)
I TOTAL VACCINE ES C 11 PATIENTS) - DOSE l I

l----------------------------------------------------------------------------1
CLINICAL
tot1PLAIHTS
l----------------------------------------------------------------------------1
I O I 1 I 2 I l I 4 I 5 I
WITH
ICDtlPLAIHTS
•••••••••••••••••••••••••••••••••••l••••••-••l••••••••••
I I
l••••••••••l••••••••••l••••••••••l••••••••••
I I I I
l••••••••••I••••••••••
I I
REACTION, LOCAL IINJECT. SITE) I 4 I 1 I 1 I 0 I 0 I 0 I I 4
, I c 40.0:0 I c 10.or., I 1 10.0;0 I c o . o;o I c o.oz1 I c o.or. , I I c tto . o;o
-----------------------------------t----------t----------1----------1----------1----------l----------
soRENESS I 4 I 1 I 1 I II I o I II
l----------l-----------
I I 4
I C 40.0iO I I 10.0?.) I I 10.0ZI I I 11 . 117.) I I O.OZI .1 I 0.07.l I I I 40 . D?. I
-----------------------------------l----------l----------l
s ysn11tc I o l l I
----------l----------l----------t----------l----------l-----------
1 I o I 1 I o I I 1
I c o.or.1 I 1 10.o;n I c 10.or.1 I I o.o:o I 1 10.or.1 I, o.or.1 I I c 10.or.,
------------------------------------------------------------------------------------
1 I I t I
lNTEGUMEHTARY SYSTEH I O I O I 1 I O D O I I 1
0.07.1 I I o.o;n I I 10.07.1 I I 0.07.1 I o.o;o f 0.07.1 I I I 10.0¼I
I I I I I
PRUIUTIS/ITCHIHS I O I O I 1 I O O O I I l
I O.OiO I I O.OY.I I I 10 . 0lO I I O.O¼I I 0.07.1 I O.OY.I I I I 10 . 0?.I
I I I I I
RUPI Rt.TffllY I o I 1 I o I o l a I I 1
o . o;n I I 10. 0Y.l I I a.or., I I O. OY.l I 10.0Y.I I o . o:o I I I 10.0:0
I I I I I
PHARYNGITIS I SORE THROATI I O I l I O I O 1 0 I I 1
I c o.or.1 I 1 10.0;0 I I o.or.1 I I o.o:o , 10.or.1 , o.oY.1 I I 1 10.or.1
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH COl1PLAINTS I 4 I 2 I 2 I O l 1 I O I I 4
I I tto.or.1 I 1 20.or.1 I 1 20.or.1 I , 0.07.1 I 1 10.or.1 I I o.or.1 I I I tto.oY.1
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
PERSONS WITH HO COMPLAINTS I 6 I 8 I 8 I 111 I 9 I 10 I I 6
I I 60 .or.1 I I ao.01.1 I I ao.or.1 I 1100.07.1 I 1 90.01.1 I 1100.or.1 I I I 60.07.1
-----------------------------------1----------I ----------I----------I----------I----------I----------I----------I-----------
PERSONS WITH NO DATA I o I o I o I o I 0 I a I I o
I I o.o;o J I o.or.1 I I o . or.1 I I o.or.1 I I o.or.1 I I o.or.1 I I , o.o;o
0
0
..0
-
'""
-
Table 6 (cont)
PATI ENT COUNT CLINICAL COMPLAINTS
STUDY 0813
TIIEATHEN'T
LOT tfJMBER CH126
DOSE 10 HCG
PAHEHT CLASS PREIMMUNE ADULTS
I . TOTA L VACCINEES ( 14 PATUNTS l - DOSE l I

l----------------------------------------------------------------------------1
CLINIC AL
COMPLA INTS
l----------------------------------------------------------------------------1
I O • 1 • Z I l I It I 5 •
MI TH
•cONPUIHTS
•••••••••••••••••••••••••---••••••l••••••••••••••••••••••••••••••••••••••••••••••••••••••I••••••••••••••••••••••••••••••••
RE ACTION. LOCAL IINJECT. SITU
I
• 2
•I 1
•I l
•I O
II O
II O
I
•
II 3
• I 14.3XI • C 7.UO • I 7.lX) I I o.or., • I 0.0)0 I I o.or.1 • • I 1!1.4)0
-----------------------------------1
SOREHESS I----------1----------
2 I 1
•----------1----------1----------1----------1----------1-----------
I l I o I o I o I I 3
• ( llt.3,0 I ( 7.lZI I C 7.lX l • I 0.0;:1 I I o.or., I I O, OiO I I I 21.47.)
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS MITH COl1PU 1NTS • 2 • l I l I D I O I o I • l
I I llt.3i0 I I 7.11.) I C 7.li!) • I O.OX) I I o . or. , I I o.or.1 I I ( 21 .t+XJ
-----------------------------------1----------•----------•----------I----------I----------I----------
PERSOHS MITff HO COt1P U INTS • 12 • 13 I U • 14 I lit I lit I----------I-----------
I I 11
I I 85 . 77.1 I I 92.91.l I I 92.9ZI • 1100.01.1 I 1100.0;:1 I 1100.07.l I I I 78.67.l
-----------------------------------1
PERSOHS MITH NO DATA I
----------l----------l----------•----------I----------I----------I----------I-----------
0 • 0 I 0 I 0 I 0 I 0 I I 0
I I 0.07.I I ( 0.07.J I ( O. OXJ I ( 0.07.J • I o.o;o I f o.or., I I f o.o;o
0
0
4
~
-
N
Table 7
PATIENT COUNT NlXIt1Ltt TEHPERATURES
RECONBINAHT HEPATITIS 8 VACCINE
STUDY : 0813
TREATMENT
LOT NUIIBER CNU6
DOSE 5 HCG
PATIENT CUSS PREIHlfiJNE ADULTS
I TOTAL VACCINEES I 11 PATIENTS) - DOSE l •

•---------------------------------------------------------------------------------------1
I DAYS POST VACCINATIOH I ~ER
"AX TEMPERATURE •---------------------------------------------------------------------------------------• MITH
CDEG F, ORAL I • D I 1 • 2 • 3 I 4 • 5 I • • NAX TEl1P
••••••••••••••••••••••.. ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••a•a
NORl1Al
•I 7
•• 9
II 10 I• 10
II 10
•• 10
•I II 7
I C 70.0lO • I 90.0iO • noo.o;o • (100.0iO • (100,0?.I I 1100.0?.I I • C 70.0i(J
I I I I I I I I
< 99 I 1 • o I o • o • o • o • I 1
I C 10.0lO • I 0.0,:1 • C 0.0?.I • C o.o;o • I 0.0XI I C o.ox, • • C 10,0,!)
• • • I • • I I
99 - 99.9 • 2 I 1 • o • o • o I o • • 2
I I 20.0XJ • C 10.0XI • C 0.0XJ • C D.OXI • C 0,0Zl I I 0.0XI I IC 20.0XI
------------------------•----------l----------•----------•----------•----------•----------1---------------------•-----------
tENPERATURE TAk£H • 10 • 10 • 10 • 10 • 10 • 10 I • 10
• C 90.9lO • C 90.9iO • C 90.9lO • I 90.9lO • I 90.9XI • I 90.9ZJ • I f 9D.9i0
------------------------•----------l----------•----------l----------l----------•----------•---------------------•-----------
TEl1PERATURE HOT TAKEN I 1 I 1 • 1 I l • l I l I • l
It 9.lXl IC 9.lXJ IC 9.lZJ I f 9.lZI I t 9.lZJ It 9.lXI I I I 9.lZl
0
0
...,
..0
... \,-
Table 7 (cont)
PATJ£NT COUNT Ml XIN\.tt TEMPERATURES
AfCOtlBI HAHT HfPl "l'ITIS 8 VACCINE
STUDT 0813
TREATtlfHT
LOT HUMBER · CM126
DOSE 10 MCG
PATIEKT CLASS PREif,tiUNE ADULTS
I TOTAL VACCINEE9 I 14 PATIENTS) - DOSE 1 I

•---------------------------------------------------------------------------------------1
I OATS POST VACCINATION I HUMBER
"AX TEMPERATURE
COEG f , ORALI
l---------------------------------------------••----------------------------------------1
I O • l I Z I 3 • 4 I 5 I I
MITH
I " AX TEMP
••-•••••••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••1ttt••••••l••••••••••l••--•••••• I••••••••••
• I • I I . • I I
NORMAL I 13 • 13 • 1Z I 12 I 12 I 12 I I u
I ( 92 • 9Y. ) • ( 92 • 9Y. I I C 85. 7Y. I • C 85. 7Y. I I I 85. 7Y. l I I 85. T/.) • I I 85. no
• • I I I I I I
< 99 I l I l • l I 2 I 2 I Z I I l
I I 7.UO I I 1.1:0 I I 7.lY. I I I 14.3Y.I I I 14.3Y.I I C 14.3Y.I I I I 7.liO
I • I I I I I I
99 - 99.9 I o I o I 1 I o I o I o I I 1
I I O. OY.) I I O. OY. ) I I 7. lY. I I I O• OY. ) I I O. o:o I I O. OY. I I I I 7. lY. I
------------------------1I ----------1.
TEMPEAATURE TAl<EH 14 I
--------l----------l----------l----------1----------1
14 I 14 I 14 I 14 I 14 I
--------------------I-----------
I, 14
I noo.0Y.I I 1100.0:0 I 1100.0;0 I 1100 . 0:0 I 1100.0:0 I n oo.o::o I I 1100.o;o
------------------------ l----------l----------l----------l----------l----------1----------1
n HPERATURE HOT TAKEN I o I o I o I o I o I o I
---------------------1-----------
I o
I I O.OY. ) I I O.OY.I I I O.OY.I I C 0.07.l I I o.o:o I C o.o:o I I t O.OY. I
0
0
...,
,0
~-
I:>
IMMl.'NOOEl'llan' OF RECOMIIISA."l'f YUS'I'
HEPA11T1S ■ VAc.c:::INE
~ -111 Dr filg 111d ~ - ~ r.,:.. 24, p 1174) ia diiny
IIQllitau ,c r Haen• btpmilia I ftCCiM "lbt iiuaam
m,.,. ia die Wbiaur YcciDc ll"Ollp - Ina plUNI d
earillg lbc Ml IIIOIIW tlll:lill tbt pllaft '1ICCiDe l"OllP, u .,_
.,_....., _ _.._ nra a ~ - - ;..Hie 1na11•.
1 " " 1 ~ a l0 111dDleetrm l!!inlffl~'llida120,<1
4w etr'rm ltcriwld ftCCiDI.
A. iadicwld ia lbc 1111h. 1111r ,-la ii a limibr 11\!dy ill -
lllaD1lnd and 9"'tC MtO:llp~ lillldl pre(lllion&la, 21-JO ,-v
efap. rntalcd-.!l1 dw-laaa-~iarac:ipima,
ef 9111 nd 10 ,ia . . _ .t,-luat , - Mpll&is I ftl:Cille
n a coaipand willl ac.nparabk p1111pnonai\Old JO IC._
elplu..-i\'ldYICCi&
\'llid mect.... - lie.._ ha 11111H1 ii tldnJ •·•

....,_ 'ftCCi-. Men ...... lrudial will .. , . . . , . .
lftl,1111 -;..HJ1 ,.,._ ud in ,a'lillma ill napilDu ,I
nambiNI! btpemio I ftCICiM. la ... - N• . -iniunlrwlu
lft-.pll,
Molrrm. na....
54\:L ~ l!GIWI
THtl,A),CET.JA!l."l"Al\" 12. I NS 109
IUOCOIII\Ui101111Aftl&ND~IIIIIAXflTUIICM1Ul'IDONIGAflWIIPo'IIMDUAU.-.'1.ft~ ■ICDNID,;Ai.,-OII
ft.AIIIIIA.111111\"11) ICIPA1"11 I 1'6CCDIII
··-- ---t
,,. ..... ._.12D_..
...,
T-•
•I
.....
Ntll'NII
11,c
.n:1a1
tGMn
Mi-
f(iMT)
..,.
.....
Aali-NII .n;,.,
t(iMT)
.,,,_
(GMT)
..fl
....
MDIIII
..
~'Ii-
CCiMT)
..
2
J
•
'"
JJ.lt l ~
to-t, . .,
.,
WIOdf'I
I a
...., ,-.P•,-------••-..,._.,
. .'SI CMl,I
,,,,.~,
141
121
ltl l
.,.,,,
114
,.,,u,,.,
w•cn.>
Ulltc,,I,)
-'" .
"
IZ
IM
18
SI
a
1a.
11'47~
....7(JM)
tWTCM1
....,lift,
1
..,.,,.,.,,
JD
.
17
7'i)
141
• V - t - • L l. -e.-ita .... ,_,.~ t--•ff.llCo&ell...... a711.
D vidson ~o Krugan s. I no~~n1c1ty of rte 1n nt ~ 1st h_P&t1t1s D v~cc1ne .

Linc t 1tes, 1:101-t.
0097b
RECOMBIRAN'i' YEAST Hl:P~TI~IS B VACCINE: SIDE EFFECTS AWC

IHMOYOCENICITY COMPlll:D ~I~H PLASMA-DERIVED HEPATITIS B VACCI~E.
Merton Davidson and Saul Xrugman
NYU Medic l Centec, HEW Yock, N.Y.
A yeast recombinant hepatitis B vaccine (Herek Let ne. 972/C-
K444) was v&luated in 187 seronegatlve health professionals, 21-
39 years of 69. Th clinical and ntibody responses were
compared with the results of previous aimil&r study using a
plasma-deriv d hep5titis B vaccin (H rck Lot no. 751).
~he vaccin was a dministered ate, l an~ 6 months to the
following tbre 9roups: l) 51 adults who r c ived a lf mcg dose
cf recombinant vaccinE;-2) 56 adult~ who received~ 5 mcg dose of
recombin nt vaccin, nd 3) 47 adults who r ceived a 29 ~cg dcse
of plasm~-derived vaccine. The three groups included medical
students, house staff, and nur11es who were of compara_ble age ancl
sex.
Results
Side effects were negligible in ll three groups. They
inoculation in about 251 of the vaeein•es in each group. No
systemic reactions were observed.
The se_roconvers ion rates and geometric mean titers are
sunwari:ed in the Table. Th results are essentially the . same for
all three groups. Under -the conditions of th is study the S meg
a nd lS mc:9 doses of recombinant hep&titis B vaccine were, just as
immunogenic as a 29 mc9 dose of plasma-derived hepatitis B
vaccine.
Comment
A recent report by Jilg et al (L~neet 1984; 2:1174-7S)
describ~ a similar study in 39 seronegative medical students and
laboratory-worke rs whose age and sex were comparable to those in
our groups. Thy stated that •the immune response in the
recombinant v&ccine group was less pronounced during the first
months than in the plmsm, vaccine group, as shown by lower
seroconversion rates and lower mean anti-HBs levels.• Our results
in 197 similar .recipients of the recombinant h patitis B vaccine
do not support this conclusion. . .
It is obvious that valid conclusions cannot be'drawn from
studi s involving either 38 or 199 vaccinees. MHe extensi ve
studies will be required to detErmine anti-HBs response and its
persistence in recipients cf recombin~nt hepatitis B vaccines.
D v1dson , Kna inant y~mit hp t1t1s Iv cc1n•: S1d Gff cts

1nd 1 not n1c1ty c Nd 1th pl -d r1vtld h l)llt1t1s 8 vacc1n~.
su 1tt for p ~11c t1on u ttyut1t1i Sc19nt1f1c PJ!i!)randm.
TABLE
Seroeonversion Rates and Geometric Hean Titers of Seronegative

Adult~ Who Received Recombin&nt Yeast Hepatitis B Vaccine (Herek
Lot No. 972/C-K444) or Plasma-Derived Hepatitis B Vaccine (Herek
Lot No. 751).
Time Recombinant He ti tu 8 Vac:ci ne

Interval HI me S me dose
anti-HBs s N Ratio anti-HBS mIU/ml S/N Ratio
(Months) reseonse GMT reseonse GMT GMT
0
l 22/51 (43%) 42 19 21/S6 (37%) ss 25
2 48/Sl (94%) 88 37 51/56 C9l%) 69 38
3 50/Sl (98%) 145 S2 52/56 (93%) 128 51
6 49/50 (98%) 321 63 53/56 (95%) 184 42
8
Vaccine given at e, land 6 months.

Time Plasma-Derived Hepatitis B Vaccine

Interval 2G 1ncg dose
ant1-HBs S/N Ratio
(Months! reseonse CMT
0
1
-
18/47 (38%)
-20
2 34/41 (79%) 37
3 45/47' (96%) 79
6 44/47 (94%) 94
7 46/47 (98%) 141
Vlilceine given t e, land 6 months.

Age ran9e: 21 39 years
oncne

doses of yeast recombinant vaccine among:
1. preimmune healthy adults
2. healthy adults immunized previously with plasma-
derived vaccine who were nonresponders (anti-HBs
negative.
VACCIME: Yeast Recombinant Hepatitis B Vaccine

Lot #972/C-K444 (10 rncg/ml)
PRIMARY Robert P. Bishop, M.D.

INVESTIGATOR: Director, Health Services
Merck &Co., Inc.
SECONDARY Edgardo P. Avancena, M.D.

INVESTIGATOR(S): Joseph C. Rogers, ~.D.
Joseph P. Romano, M.D.
Merck & Co., Inc.
West Point, PA & Rahway, NJ
STUDY LOCATION: Merck & Co., Inc.

Mercie & Co., Inc.
Rahway, NJ 07065
25471/cfs
12/20/85
Study 817
STUDY POPULATION: The study population will consist of 40-50 healthy

adults of either sex (excluding pregnant females). who
are employees of Merck & Co., Inc. Half of the
population will consist of persons with pre-existing
hepatitis B antibody which may be either naturally
acquired or plasma vaccine induced. The other half
wi 11 consist of persons who have been vaccinated with
plas111a vaccine but failed to develop detectable
antibody to hepatitis 8. All participants must be
negative for anti-HBc and HBsAg, and have a normal ALT
1evel.
PROCEDURE: Study participants are allocated to one of two
regimens as shown below. All injections are
intramuscular.
Tirae of
_ Group Dose Vaccination
l. Preinvnune 5 1.0 ml (10 mcg) 0
2. Nonresponders 4 1.0ml (10mcg) 0, 1 &6 mos.
Vaccinees are asked to record their temperature da11y

for five days after each injection and also to record
any local or systemic complaints they may have during
this period.
participant approximately 2 weeks before the first .
obtained at l, 2. 3, 6. 8, 12 and 24 months. The
samp·les are assayed for HBsAg, anti-HBc, anti-HBs.
yeast antibody and ALT. Those with anti-HBs titers>
mIU/ml may be tested for the proportions of anti-! and
anti-g_ activity.
25471-2/cfs
12/20/85
009M
Study 817
RESULTS: PREIM U~E ADULTS:

10 mcg Lot 1972/C-K444 at time 0
l. Number Vaccinated: s
All five vaccinees showed a large boost in
anti-HBs following vaccination. Table 1 shows
individual ant1-HBs responses for up to 12 months
of follow-up.
Clinical follow-up data are available for all 5
vacc1nees for the five days of follow-up
following vaccination. Specific complaints and
maximum temperatures reported during that time
are provided in Tables 2 and 3.
Type of Complaint Frequency in %

Injection Site 20 (l/5)
Systemic 0 (0/5)

2547!-3/cfs
12/20/85
Study 817
Table 1 ·
Antibody Responses Among Pre;munne Adults Follow;ng Vacc;nation
with a Single 10 mcg Dose of Yeast Recombinant Hepatitis B Vaccine
Lot 1972/C-K444 in Study 817
Anti-H8s (mIU/ml)
Case I. _f.!:!_ 1 Ho. 3 mo. 6 mo. 12 mo.
b)(6)
4* 15.2 105.7 150.0 26.S
4* 810.9 404.3 99.S 52.S
8* 475 456.1 355.72 62.3
11.5 350.3 50.7**
4* 1734 .4 2063.4 1119.3 318.6
GMT (mlU/ml) 5.7 317 . 4 402.5 197.6 72.5
*Approximate mIU/ml titer+ 4)

'"'Late bleeding at 8 months.
25471-4/cfs
12/20/85
Table 2
PATIENT COUNT CLINICAL tot1PLAIHTS
STUOY t 0817
TREATt1£HT
lOT NUMBER CKC.44
DOSE 10 tlCG
PATIENT CLASS: PREIMnUHE ADULTS

1--------------------------------------------------------------------
I DAYS POST VACCINATIOH
·-------1I NU118ER
CLINICAL 1---------------------------------------------------------------------- ------I MITH
COMPLAINTS I O I 1 I 2 I l I 4 I 5 I ICottPLAINTS
••••••••••••••••••••••••••••••-•• Il••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I
REACTION, LOC AL IINJECT. SITEI I l I l I O I o I O I O I I 1
I 1 20.01.1 I I 20.01.1 I I 0.01.1 I 1 0.01.1 I 1 0.01.1 I 1 0.01.1 I I c 20.01.1
-----------------------------------1----------l----------l----------t----------1----------l----------l----------t-----------
sORENESS I 1 I 1 I o I o I o I o I I 1
I 1 20.01.1 I c 20.0%1 I I o.o:o I 1 0.01.1 I 1 0.01.1 I · 1 o.o:o I I c 20.0:0
-----------------------------------1----------I----------I----------I----------I----------I----------I----------I-----------
PERSONS MITH COMPLAINTS I 1 I 1 I O I D I O I O I I 1
I I 20.07.1 I I 20.07.1 I I 0.07.1 I I 0.07.1 I I O. OY.I I I 0.07.) I I I 20 . 0Y.I
-----------------------------------l----------1----------l----------l----------1----------1----------1----------I-----------
PERSONS WITH NO COt1PUIHTS I It I It I 5 I 5 I 5 I 5 I I <t
I C 80.0Y.I I C 80 . 0Y.I I 1100.0Y.I I 1100.0Y.I I (100.07.1 I 1100.07. ) I I I 80.07.1
-----------------------------------t----------l----------l----------l----------1----------1----------1----------I-----------
PERSONS WITH HO OATA I o I a I o I o I o I o I I o
I I o.a:o I I 0.07.1 I I 0. 07.1 I ( a.DY.I I I 0 . 07.1 I I o . o:o I I I O. IIY.I
0
0
-0
~
"'
Table 3
PATIENT COUHT 11l Xl111.t1 TEl1PERATURES
RECOMBINANT HEPATITIS B YACCIIIE
STUDY 081 7
TREATt1ENT
LOT IM1BER CK't"
DOSE 10 NC6
PATIENT CLASS PREirHJNE AD\R.TS
• TOTAL VACCINEES ( 5 PATIENTS) - DOSE l I

•---------------------------------------------------------------------------------------1
• DAYS POST VACCINATION • NUHBEA
11AX TtMPERAT~E
IDE6F,ORALI
l---------------------------------------------------------------------------------------1
• 0 I l I Z • 3 I 't I 5 • I WITH
l11AXTf11P
••••••••••••••••••••••••l••••••••••l•••••••••••••••••••••l•••••••••••••••••••••• •••••••••• l••••••••••l•••••••••• I••••••••••
I I • I I I I I
< 99 I s I s I s I 't I s I s I I s
I 11 00.07.1 I 1100.01.1 • 1100.07.1 I 1100.0:r.1 • 1100.01.1 I 1100.0;0 I I 1100.01.1
------------------------1----------1
TEMPERATURE Tll<EH • 5 I
----------l----------f----------
5 • 5 • 't
l----------l----------l---------------------l-----------
I 5 I 5 I I 5
I 1100 ; 01.1 I 1100.01.1 I 1100.07.1 I I ao.o;o I 1100.0:r.1 I 1100.01.1 • I 1100 . 01.1
------------------------l----------•----------l---------- l----------l----------•----------I---------------------I-----------
TE11PERATURE NOT TAl<EH • o • o I o • 1 I a I o I I o
I 1 0.01. 1 I , o.o;o I , 0.01.1 I r 20.01.1 I I o.o;o I 1 1 .0:r.1 I I 1 0.0:r.1
~
0
-a
QI)
~
CHRONIC CARRIERS
Chronic Carriers - Population Summary
One study (#854) has been initiated to determine the safety of the vaccine for
persons who are chronic carriers of HBsAg and to determine whether vaccination
can eliminate the carrier state in these persons. Eighteen adult chronic
carriers (positive for HBsAg for at least one year) have been scheduled to
receive six 10 mcg injections of yeast i-ecOlllbinant hepatitis B vaccine at
monthly intervals. Three participants have received all six injections;
eighteen have received at least four injections. The study continues in
progress.
To date, none of the chronic carriers has become negative for HBsAg. The
vaccine has been well tolerated. No serious adverse experiences attributable
to vaccine have been reported.
24231/5
1/8/86
Study 854
I
,,
Study 854.

recombinant hepatitis B vaccine in the following adult
populations:
l. Chronic Carriers of HBsAg
2. Healthy Hyporesponders to Plasma-Derived Vaccine.
3. Healthy Nonresponders to Plasma-Derived Vaccine.
4. Healthy Trans1 ent Responders to Plasma-Derived
Vaccine.

PRINCIPAL Jules D1enstag, M.D.

I NVESTI GA TOR: Associate Professor of Medicine
Massachusetts Gen. Hosp.
Boston, MA 02114

Mass. General Hosp.
Fruit Street
Boston, MA 02114
Clinical &Research Fellow
Mass. General Hosp.
Boston, MA 02114

Fruit Street
Boston, MA 02114 ·
DATE INITIATED: October 14, 1984
23881/861/1
1/3/86
Study 854
STUDY POPULATIONS: The study population will consist of adults of either

sex (excluding pregnant women) who can be classified
into one of the following groups:
Number of
Group Subjects Qualifications
Carriers 10-15 Chronic carrier of HBsAg for at
least one year, with no s 1gns
or symptoms of chronic liver
disease. and a stable ALT level
less than 3 times the upper
limit of nonnal.
Hypo- 15-20 Healthy adults who have had only
responders a low level anti-HBs response
(positive titer obtained in at
least 2 successive bleedings)
to a complete 3 injection
regimen of plasma derived
hepatitis B vaccine. (maximum
antibody t ter 8-36 when
11easured in (b[ {4} RIA units.
2.1-9 . 9 when measured 1n terms
of S/N ratio, or <10 mIU/ml]
Non- 15-20 Healthy adults who had a single
responders post-vaccination blood sample
with an anti-HBs titer in the
range S/N = 2. 1-9. 9 followed by
additional samples all with S/N
less than 2.1 as well as
persons whose post-vaccination
blood samples all had anti-HBs
titers of S/N less than 2.1
after receiving a 3 injection
series of plasma derived
Transient 10-15 Healthy adults who had at least
Responders one blood sample with an
ant1-HBs titer of S/N >10
following a 3 injection series
vaccine but have subsequently
lost antibody (S/N <2.1).
23881/861/2
1/3/86
Study 854
PROCEDURE: Prior to vaccination, each part1-c1pant wi 11 be

screened for HBsAg, antf-HBc, anti-HBs and ALT level.
A serum pregnancy test will also be performed for all
women of childbearing age. Vaccine is administered
intramuscularly according to the following schedule.
Group Vaccination Regimen

Carriers l .0 ml ( l O mcg HBsAg) at time o. 1•
2, 3, 4 and 5 months.
Hyporesponders 1.0 ml (10 mcg HBsAg) at time 0
Nonresponders 1 .0 ml (10 mcg HBsAg) at time 0, 1
and t, months.
Transient 1.0 ml (10 mcg HBsAg) at time 0.
Responders
The vaccine recipients are asked to record their

note any 1oca 1 or systemic co111> 1a i nts. Unexpected or
serious reactions will be reported to the study
physician innediately.
Follow-up blood samples w111 be obtained from carriers
monthly for b months and at 9 and 12 months: from
hyporesponders and transient responders at 1, 3, 6, 9,
12 and 24 months and; from nonresponders at 1, 2, 3,
6, 9 months, and at 12 and 24 months from those who
have seroconverted by 9 months. Samples are assayed
for HBsAg, ant 1-HBc, ant 1-HBs, and Al T by Or.
Dienstag. Samples may also be assayed at MSDRL for
yeast antibody and for the proportions of anti-HBs
specific for the! and~ detenninants of HBsAg.
238BI/8bl/3
1/3/86
Study 854
RESULTS: CARRIERS
10 mcg Lot #979/C-K564 at o. 1, 2, 3, 4, and 5 months.
1. Mumber vaccinated:
Injection No.
_ l ___
2_ __3_ __4_ ___L _6_
18 18 18 18 12 3
None of the carriers has yet become negative for
HBsAg.
participants after injections one through four,
12 participants after injection five, and for 2
subjects after injection six. The overall
frequencies of complaints are presented below:
Freo&»n~ in\ b~ In~tion

r.t.ftlaint 2 3 4 5 _6_
Injection 22(4/18) 17(3/18) 22(4/18) 22(4/18) 8(1/12) 0(0/2)

Site
Systemic 17(3/18) 11 (2/18) 17(3/18) 11(2/18) 17(2/12) 50(1/2)

There were no serious or alarming react1ons
23881/861/4
l/3/86
Table l
PAlIENT t ~ CLINlC4L COtfflLAINTS
AECOH8IHANT HEPATt 1 1S 8 VACCINE
STUOY 0854
TAEATttENT
LOT NUtlBEA Cl<564
DOSE 10 11CG
PATIENT CLASS CIIROIUC CARRIERS
I TOTAL VACCIN£ES I 18 PATIENTSI - DOSE 1 I

t----------------------------------------------------------------------------1
I DAYS POST VACCINATION I NU11BEA
l----------------------------------------------------------------------------1
CLINICAL
COMPLAINTS I
,
I
O I
I
1
,I
I
Z I
I
J
, •
I
4 •
,5 I
WITH
IC011PLAINTS
................................... .......... ......•... .......... ........................................... ..........
I I
,
•
REACTION, LOCAL fINJECT. SITEI • 3 I Z • Z I Z I O I O I • <t
• I 16.71) I C 11.lXI I ( 11.lXI I I 11.111 I ( o.ox, IC o.ox, I I l ZZ.ZXJ
-----------------------------------1----------t----------1----------1----------t----------1----------•----------1-----------
SORENESS I ] I Z I 2 I Z I O I O I I lt
I C 16.71) I C 11.11) I C 11.111 I C 11.111. l O.OXJ IC O.OXJ I • C ZZ.ZX)
I I I I I I I I
HE11UOttA I O I 1 I D I D I I D I O I , 1
I I o.o;o t c 5.611 t t 0.011 t c o.o;o t , t l 0.011 I I c s.6iO
o.ox,
-----------------------------------1------·
srsrEMit I l
---t----------l----------t----------t----------1----------1----------1-----------
I 2 I D I O I l I 1 I I 3
I l 5.611 I c 11.llJ I t o.o:o I l O.OXJ I I 5.9%) I I S.6X) I I « 16. 7XI
WHOLE BOOY/GEHEAAL I l l 0 0 0 0 l
5.6XI ( 5.67.1 ( a.ox, I o.ox, ( O.DXI ( O.OXI ( S.611
F ATIGUE/ldlEAl(NESS
•( l
5.6XI
l
5 .6Y. I
0
0.011 I
•
D.OY.I I
0
O.OXJ
0
O.OXI l
l
S.6XI
'
( (
DIGESTIVE SYSTEM I
(
0
O.OY.J (
l
5.6Y.I I
0
O.OY.J I •
O.OXJ I
1
5.9Y.I (
l
S.6XI
2
( 11.1)0
DIARRHEA I 0 1 0 0 0 0 1
•• 0:1.) I S.6Y.I I 0.0:1., ( 0.0:1.) ( a.ox, I 0.0:1.) l 5.6:r.J
NAUSEA I 0 D 0 0 1 1 1
( o.o:o l O.DX I ( o.ox, ( o.o:o ( 5.9)0 I 5.67.) I 5.6)0
DININISHEO APPETITE I O I O • 0 • 0 • 1 • O I I l
I ( 0.07.1 I I O.OXI I I o.o:o I I o.o:o I I 5.91.I I ( o.ox, I I I S.6i0
-----------------------------------1----------•----------l----------l----------l----------t----------t----------•-----------
PtRsotlSMITH COMPUIHTS I lt I 4 I Z I 2 I l I l I • 7
I , zz.zx, I , zz.z;o I c 11.111 I , 11.11., I , s.9"/.J I , s.6Xt I I , 3e.-,,:,
-----------------------------------1----------1----------1----------1----------1----------1----------1----------1-----------
PtASOHS NITH NO Cot1PLAIHTS I llt I 14 I 16 I 16 I 16 I 17 I I 11
I I 77.&XI I I 77.81.I I I 88.9Xt I I 88.91.t • I 94.UO I I 94.47.1 I I I 61.17.1 0
0
-0
3)
,0
...
Table l (Contd)
REC011BINANT HEPATITIS B VACCINE
STUDY flB54
TRUTttENT
LOT ~18ER CK564
DOSE 10 t1CG
PATIENT CUSS CHRONIC CARRIERS
I TOTAL VACCltlEES C 18 PATIEHTSI - DOSE l I

1----------------------------------------------------------------------------I
I DAYS POST VACCIHUION I Hlltll3ER
CLINICAL
. CDt1PlAINTS
1----------------------------------------------------------------------------I
I O • 1 I 2 • 3 • 4 I 5 I
WITH
I CotlPLAIHTS
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------l----------l----------1----------1----------1----------l----------1----------I-----------
PERSONS WITH NO DATA I 0 I 0 I O I O I 0 I O I I 0
·1 C O.OY.l I C D.OY.l I C O.OY.I I C O.OY.l I C O.OY.I I ( O.OY.I I I ( o.o:o
0
0
,0
.l)
0
.,,
Table l (Contd)
PATIENT ~OUHT CLINICAL CONPLAIHTS
RECOMBIHAHT HEPATITIS 8 YACCIHE
STUIIY 0854
TRUTHENT
LOT HUMBER CK564
DOSE 10 t1CG
PATIENT CLASS CHROHIC CARRIERS
I TOTAL YACCIHEE5 l 18 PATIEHTSI - DOSE t I

l----------------------------------------------------------------------------1
I DAYS POST VACCINATION I tMIBER
CUNICAL
COl1PLAIHTS
l----------------------------------------------------------------------------1
I. D I 1 I Z I 3 • ~ I 5 I
WITH
ICOHPLAINTS
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l•••••••••••••••••••••I••••••••••
REACTIOH, LOCAL IINJECT. SITEI
•• Z
•• 3
I
I Z
•I . 1 II O
I
I D
I
I
I
I 3
• ( 11.11.) I ( 16.7iO It 11.liO It 5.6iO I ( 0.01.1. I o.o;o I It 16.7iO
-----------------------------------1----------l----------•----------l----------l----------l----------l----------l-----------
sCl!EHESs I 1 • 2 I 1 I 1 I O I O I I 2
I t 5.61.) • ( 11.liO I t 5.67.) I t 5.111.1 I t 0.0iO I t o.o;o I I I 11.liO
I I I I I I I I
UMJERUESS I 1 I 1 I l I O I O I O I I 1
• t 5.67.J It 5.67.J I t 5.67.1 I t 0.01.1 I t 0.01.1 I t 0.01.1 I • l s.111.J
SlolELLINS
I
• 2
•I l
II o I
• o I
I o I
I D
II II 2
I I 11.11.) I t 5.117.) • I D,0:1.1 I t 0.07.) I I o.o:o I I 0.D:I.) I I I 11.li!I
-----------------------------------1----------l----------l----------l----------l----------l----------•----------l-----------
srsnt11c I l I 2 I 0 I O I O I 1 I I 2
I t s.61.1 I t 11.11.1 I I o.ox, I t 0.01.1 I < o.ox, I t 5.61.) I I I 11.1:1.,
WHOLE BODY/G(NtRAL I 1 0 0 0 0 D l
5.6iO ( 0.0iO ( o.o;o ( o. 01.) ( 0.Oi'-1 ( o.o;o I 5.6:I.)
SWEATING I 1 0 0 0 0 D l
5.67.1 ( o.o;o t 0 .01.1 ( 0.0i!I I o.o;o I 0.0XI I 5.61.)
INFECTIOUS SYNDRot1£S I 0 D 0 0 0 l 1
t 0. OX I ( 0.0iO t 0.0iO t 0.01.) t 0.01.) I 5.61.I ( 5.6)0
IHFLUENl!A, HOS I 0 0 0 D 0 1 l
( t.01.1 l 0.01.) ( 0.01.) ( o.o;o l •• 01.) I 5.67. I C 5.6iO
DIGESTIVE SYSTEM I 0 l 0 0 0 0 1
It 0. 01.) ( 5.61.) ( 0.0if.l ( o. 01.) l 0. 01.) ( 0 .01. I l 5.6½1
I
OTHER I 0 1 0 0 0 0 1
I l 0. 01.) ( 5. 61.) ( o.o;o ( 0.0)0 l 0.01.) ( o.or., ( 5.6½ I
I
NERVOUS SYSf£11 I 0 l 0 0 l
( o. 01. I ( 5.61.) ( 0.0)0 (
'
0.0iO l
0
0.OiO l o.or., l 5.61.1 0
0
,D
"'
,-
,,
Table l (Contd)
PATIENT COUNT CLINICAL CDt1PLAINTS
RECOl18INANT HEPATITIS 8 VACCIHE
STUDY 0854
1REA1t1EtlT
LOT NUtff'IER Cl<.564
DOSE 10 HCG
PATIENT CLASS CHRONIC CARRIERS

Il----------------------------------------------------------------------------1
DAYS POST VACCINATION I NI.Jtffl! R
l----------------------------------------------------------------------------1
CLINICAL
COMPL AINTS
................................... ,I
I..........
O
I
I•..........
1
I
,
I..........
2
I
l
I
,
I.......... ,
I..........
4
I
5
I
,
I..........
I
, , WITH
I.......... lt011PLAINTS
......... ~
VERTIGO/D I ZZINESS I O I 1 I O f O I O I O I I 1
I I O.OZI I 1 5.6ZI I ( O.OZ ) I I O.OZ) I ( O. OZ) I C O. OZ I I I ( S.6ZI
-----------------------------------1----------I---------- I----------I----------I---------- I----------I----------I-----------
PERSOtlS WITH COMPLAINTS I 3 I S I 2 I l I O I l I I 5
I I 16.71.l I c 27.81.l I c 11. 11.1 I I S.61.1 I I 0.01.l I I 5.6Y.I I I c 27 . 8Y.I
-----------------------------------1----------
PERSOHS WITH NO CONPU INTS I 15
I----------I----------I----------I----------I----------I----------
I 13 I 16 I 17 I 18 I 17 I
I-----------
I 13
I t 83.lY.) I I 72.27.1 I t 88.9ZI I I 94 . 41.I I uoo.o;o I I 94.41. I I I I 7Z.21.I
-----------------------------------t----------
PERSCffl WITH HO DATA I O
l----------l----------
I o I o I
t----------t----------1----------1
o I o I o I
----------1-----------
I O
I C 0.07.I f ( 0.07.1 I I 0.07. 1 f I O.OY.I I I 0 . 07.) I ( O.OY.) I I ( O.OZ )
0
0
.0
.0
rv
,,,
Table 1 (Contd)
PATIENf COUNT CLINICAL CONPLAINTS
RECOl18IHAHT HEPATITIS 8 VACC114E
STUDY oas,
TRUTl1EHT
LOT I-Ml8ER CK564
DOSE 111 MCG
PATIENT CLASS CHRDIUC CARRIERS
I TOTAL VACCIHEES f 18 PATIENTS) - DOSE J •

1----------------------------------------------------------------------------•
• DAYS POST VACCINATION • HUMBER
CLINICAL
COMPLAINTS
1----------------------------------------------------------------------------•
I O I 1 • 2 • 3 • , I 5 I WITH
IC011PLAINTS
•••••••••••••••••••••••••••••••••••l••••••~•••l•••••••••••••••••••••l••••••••••l••••••••••l••••••••••I•••••••••••••••••••••
RUCTION, LOCAL !INJECT. SIT£)
II 3
•I 2
•I 2
•I 1
I
I O
II o II •
I 4
I C 16.77.) I C 11.UO I C 11.17.) I I 5.6i0 I I 0.07.) I C a.ox, I I C 22.2;0
---------------------- - ------------1----------I----------I---- ------I -- - - ------I---------- I---------- ----------1-----------
SOREHEss I 2 I 1 I 1 I 1 I o I o I 1
I c 11.121 I c 5.67.1 I c 5.621 I , 5 . 6ZI I , o.ox1 I c a.oz, I c 16.121
I I I I I I I
TENDERNESS I l I 1 I 1 I o I O I o I l
IC 5.67.I IC 5.~7. 1 IC 5 . 6ZI I C O.OX) I C O.OX) I C a.ox, I C 5.6Z)
I I I I I I I
NDOULE F0Rl1Artl»f I l I 1 I 0 I O I O I O I 1
I C 5.6XI I C S.6Xl I I O.OXI It O.OXI I C O.OXI I t D.OZI I C 5.6Xl
-----------------------------------1--------
sysn111c I 2
·-1----------1----------1----------I
I 1 I o I 2 •
----------I----------
o I 1
----------l-----------
I 1
It 11.lXI IC S.67.1. C O.OZ> IC 11.lXI IC o.o:o IC 5.67.1 IC 16.7i0
I
MIIOLE BODY/GENERAL l I 0 0 l 0 0 I I 2
• 5.6XI I C O. OXI ( O.OX) ( 5 .67.) I o.o;o C O.OXI I I C 11.lXI
I I
FATIGUE/WEAKNESS I 0 0 0 l 0 0 I I l
O.OXl ( o.o;o ( O.OZI I 5.6Xl I O.OZ) ( 0.0;() • I I S.67. l
I I
HEADACHE l 0 0 0 0 0 l
( S.6Xl ( 0.0;() ( o.ox, ( O.OlO ( 0 .OX l I o.or.1 I • ( 5.67.)
I
INFECTIOUS SYNl>ROtreS 0 1 0 0 0 0 I 1
0.07.1 C 5.67.) ( O.OXI C o.o;o I o.o;o I o.o;o I I 5.6;()
INFLUENZA, NOS
' 0 1 0 0 0 0
I
I l
I O. OXI 5.67.1 O.OXI O.OXl 0.07.) I O. OXl • S.6l0
' ' '
( (
I
RESPIRATORY 0 0 0 0 0 l I 1
( o. o:o o.o;o O.OXI O.OXI I 0.0)(1 I 5.6r.1 I
' ' 5.67.1
( (
I I
UPPER RESPIRATORY INFECT., NOS 0 0 0 0 0 I l I 1
O.OXI C 0.07.I I 0.07.1 I 0.0)(1 I o.o;o I f S.6l0 I ( 5.6XI
0
0
.(I
,0
VI
,
Table I (Contd)
PATIENT C~T CLINICAL COHPLAINTS
RECotlBIIIANT HEPATITIS B Vl CCIIIE
STUDY 0854
TREATMENT
LOT tlUlfflER CK5611
DOSE JO MCG
PI\TIEtfT cu ss : CltROIIIC CARRIERS

l----------------------------------------------------------------------------1
CLINIC~L 1--------------------------------------------------------- ------------------- I WITH
COMPU IHTS I O I 1 I 2 I 3 I 4 I 5 I ICot1PlAINTS
•••••••••••••••••••••••••••••••••••l••••••••••l••••••••••l••••••••••l•••••••••• l••••••••••l••••••••••l••••••••••I••••••••••
I I I I I I I I
DIGESTIVE SYSTErt I 1 I 0 I 0 I 1 I O I 0 I I 2
I I 5.6::0 I I o.o::o I I o.or. , I I 5.67.J I I 0.07.1 I I o.07.I I I 1 11 . 17. l
I I I I I I I I
NAUSEA I 1 I 0 I o I o I o I o I I 1
I ( 5.67.) I I 0.07.) I ( 0 . 07.1 I I 0.07.) I I a.oz, I I 0.07. 1 I I I 5 . 67.1
I I I I I I I I
OTHER I a I o I o I 1 I o I o I I 1
I I o.o,o I I o.o:o I I o . o;o I t S.6lO I , 0.07.1 I I o . o;o I I 1 5. 67.I
-----------------------------------1
PERSONS WITH CONP U INTS I
----------l----------1----------I----------I----------I----------I----------I-----------
5 I 3 I 2 I 2 I O I 1 I I 5
I I 27.87.1 I I 16. 77.1 I I 11.17.1 I t 11 .17.1 I I 0.07.I I I 5.67.1 I I I 27 . 87.I
----------------------------------- 1I ----------I----------I----------I----------I----------I----------I----------I-----------
PERSotlS WITH NO COMPll IHTS 13 I 15 I 16 I 16 I 18 I 17 I I 13
I I 72,27.) I ( 83.3::0 I I 88.9)0 I I 88.97.) I 1100.0:0 I I 94 . 47.1 I I I 72.2XI
----------------------------------- l----------l----------l----------l----------1----------1----------1
PERsot•s WITH HO DATA I o I o I o I o I o I o I
----------I-----------
I o
I I o . o::o I I o . oz1 I I o.oz, I I o.o,o I I o . ox, I I o . oz1 I I I o.o;o
0
0
-0
,0
b
.,.
Table 1 (Contd)
PATIENT CQ\A,fT CLINIC l L COttPLAINTS
REC0!18IIIAHT HEPATITIS 8 VACCIIIE
STUDY 0854
TREAfflENT
LOT tlUI IIER CK564
DOSE lO t1CG
PATIENT CLASS: CIIROtlIC CARRIERS

1----------------------------------------------------------------------------I
I DAYS POST VACCINATION I tl\JM8ER
CLINICAL ·
COMPLAINTS
• ---------------•-- - ---- - ---··· · ·-·----- - ------------------------------------•
• 0 • 1
I
I 2
I
• 3 • 4 I 5 •
.......................................................................................... ..........•..........•..........
I I I
,
WITH
ICOttPUINTS
I I I
RE ACTION. LOCAL IINJECT. SITE I I 3 I 4 • D I D • D I D I I 4
I , u.n1 I 1 22.2x, • 1 ,.ox, I I o.ox1 I , o.ox, I , o.ox1 I I , zz.z;o
-----------------------------------•----------•----------1----------•----------1----------•---------- 1---------- 1-----------
SORENESS I 2 I 3 I D I D I D I o I I 3
1 , 11.1x1 1 c u,.1x1 I , ,.ox, I , 0.0;:1 I , o.o;:, t , o.o;:, 1 I , 16.1X 1
I I I I I I I I
TEtmERHESS I 1 I l I O I D I O I O I • ' l
II 5.6XI I I 5 . 6XI I l O.OX> I I O.OX) I I O.OX) I I O.OXI I II 5.6Xl
-----------------------------------1----------t----------l----------•----------•----------
svsnMIC I 1 I O I 1 I O I O
l----------•----------•-----------
I O • I 2
I ( 5.6Xl I I O.OXJ I l 5.6XJ I I O. OXI • I O. OXI I I O. OXI • I I 11 .lX J
----------------------------------------------------------------------------------------------------------------------------
WHOLE BOIJY/GENEA AL •I 1 0 0 0 0 • 0 l
5.6XJ ( o.ox, I o.ox, O.OXJ I D.OX ) •I I O.OXJ ( 5.6XI
FATICUE/MEAKHESS I l D D
' 0 0 0 1
5.67. ) 0.07.) O.OXI ( O. OXI O.OXJ ( O.OXI ( 5 . 6;()
ITCHING, FACIA L I 1
' D
' 0 D
' 0 0 1
5.6;( ) D. 07.l 0.07.) o.o;o O.Oi!I a . ox , 5.67.)
'
( (
' '
(
DIGESTIVE SYSTEM I 0 0 1
' 0 0 0 l
O. Oi!l ( O.OXI ( 5.67.) ( 0.07.) ( O.OXJ ( o.o;o ( 5.6XJ
OTHER I 0 0 1 0 0 0 1
O. OXI o. 07.) ( 5 . 67.J 0.07.1 o.o;o O.OXJ ( S.6Xl
' ' '
(
N£RYDUS SYSTEM I
' 1
I
I O I O I O I O I o I I l
S.6X l I I O. OXJ • I O.OXJ • I O.OXI • I O.OXJ • I O. Oi!l . I I S. 6XJ
I I I • I • I
VERTIGO/OI ZZIHESS • 1 I D • 0 I O I O • 0 I I 1
I c 5.6lO I I o.o:r., I , o.o;o I , o.ox, I I o.ox, • , o. o;o I I , 5.6Xl
-----------------------------------1----------I----------I----------I---------- I----------I---------- I---------- I-----------
PERSOHS MITH COMPUINTS I lt I 4 I 1 I O • 0 I O I I 5
I I 22 . 27.) I I 22.2%) I I 5.67.) I ( 0 . 0%) I I 0.0%) I ( 0. 07.l I I I 27.ex, 0
0
-0
-0
I.It
.,
Table 1 (Contd)
PATIEIIT COUtlT CLINIC AL COHPLAINTS
RECOttBINANT HEPATITIS B VACCIUE
STUDT 085ft
TRUTHEHT
LOT N\Jtt8ER Ck564
DOSE 10 ttc:G
PATIENT CLASS CHAOHIC Cl RRIER!I
I TOTAL VACCINEE!I I 18 PAT IENTS I • DOSE ft I

l----------------------------------------------------------------------------1
I OATS POST VACCIHAllON I tM1BER
CL I NlC ll
COMPLAINTS
l----------------------------------------------------------------------------1
I 0 I 1 I 2 I 3 I 4 I 5 I
WITH
ICOMPLAIHT!I
•••••••••••••••••••••••'"'••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••l••••••••••I••••••••••
-----------------------------------1----------l----------l----------l----------1----------I----------I----------
PERsOIIS WITH HO Cot1PllINTS l 1ft I 1ft I 17 I 18 I lB I 18 I
I-----------
I 13
I I 77.8i0 I I 77.87.1 I I 9lt.tt7.I I noo.01.1 I noo.01.1 I U00.07.1 I I I 12.21.1
-----------------------------------1
PERsotlS WITH HO DATA I
----------
O
I----------
I O
I----------I----------I----------
I O I O I O
I----------
I O
I----------
I
I-----------
I 0
I I 0.01. 1 I ( 0.01.J I I 0 . 01.) I ( 0.01.1 I C 0.01.) I C o.o;o I I I o.o;o
0
::,
.0
4J
O'-
.,
Table I (Contd)
RECotl8mANT HEPATITIS 8 VACCitlE
STUDY 0854
TREATHENT
LOT IM18ER CKSft4
DOSE 10 MCG

l----------------------------------------------------------------------------1
I DAYS POST VACCJHATIOH • HlfflER
CLINICAL
COt1PUIHTS
1----------------------------------------------------------------------------•
I O • l • 2 • 3 I • I 5 I WITH
ICOHPLAIHTS
•••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l••••••••••I••••••••••
I I I I I I I I
REACTION, LOCAL I INJECT. SITEI I 0 I l I O I O I O I 0 • I 1
I, 0.0;,:1 I, a.3;,:1 I, 0.0;,:1 I, 0.0;,:1 Ic 0.0;,:1 • , 0.0;,:1 I I, a.3;,:1
-----------------------------------l----------•----------l----------l----------•----------l----------l----------l-----------
so11eHEss • o I 1 • o • o I o • o I I 1
I I O.Oll I ( a.3l) I ( o.o;o • ( 0.0iO I ( o.o;o I I o.o:o I • I a.3i0
-----------------------------------1----------l----------l----------l----------l----------l----------l----------l-----------
sysrEHIC I l • 2 I l I l I l I l I I 2
I I 8.3l> IC 16.7)0 I l 8.]ll I l 8.3l> I l a.3i0 I I a.37.1. I l 16.n>
----------------------------------------------------------------------------------------------------------------------------
I
MttOLE BODY/GENERAL I l II II II 0 0 1
8.37.> C o.o;o ( o.o;o ( 0.0iO ( o.o::o I o.o;o ( 8.3ll
f' ATIGUE/NEAl<HE SS I 1 0 0 0 0 0 1
a. 3;,:, ( o.o;o ( 0.07.J I o.o;o ( 0.07.J ( 0.07. J ( 8.37. >
IHf'ECTIOlr.l SYNDROMES I 0 1 0 0 0 0 1
0.07.J ( 8.3ll ( O.Oi!J ( 0.07.1 ( 0.07.) ( o.o;,:, ( a.1;,:1
INFLU£NZA, NOS I 0 I 0 0 0 0 1
0.07.J ( 8.3ll I 0.0;,:1 I o.o;o C o.o:o ( 0.07.) C 8.llO
DIGESTIVE SYSTEN I 0 l 1 l 1 l l
o.o:o 8.3:1.1 ( a. 1:;i1 8.JY.I ( 8.3i!J ( 8.Ji!I C 8.11/.1
'
(
DYSPEPSIA/HEARTBURN I 0 0 0 1 a a 1
o.o:o o.o:o ( 0.07.1 8.3i0 o.o:o O.Oll a.1;i1
OTHER I o I
' l I l I
' o I
' l I
' l I I
' l
I « o.o;o I I a.37.J I « a.37.> I « o.o;o I « a.1:1.1 I I a.1;0 I I « a.1:0
-----------------------------------•----------l----------•----------l----------1----------1----------1----------I-----------
PERSONS MITH COMPLAINTS I l I 2 • l • l I l I l I I 2
I c 8.3:!I I c 16.7Y.I • I 8.JY.J • I a.1;,:1 I f 8.3%) I « a.1;0 I I « lft.7?.I
-----------------------------------1----------l----------l----------l----------l----------l----------•----------I-----------
PERSONs MITH HO COl1PLAIHTS I 11 I 10 .I 11 • 11 I 11 I 11 I • 10
I , 91,7;0 I , a:s.1:;o I , 91.7:1.J I , n.1:1.1 I t 91.77.1 I « 91.7:1.1 I I c e:s.1:1.1 0
0
,0
-D
"'4
.,
Table 1 (Contd)
PATIENT col.NT CLINICAL COttPLAINTS
RECOt18INAtlT HEPATITIS 8 VACCIUE
STUDY 0115ft
TREATMENT
LOT NUHBER Cl<564
DOSE 10 MCG
PATIENT CUSS ClfROltIC CARRIERS
I TOTAL YACCINEES I 12 PATIEHTSI - DOSE 5 I

•
l----------------------------------------------------------------------------1
DAYS POST VACCINATION • NUl1BER
CLINICAL
COIIPUINTS
•----------------------------------------------------------------------------1
I O • 1 I 2 I 3 I 4 • 5 I
WITH
•c011PUIHTS
••••••••••••••••••••••••••••••••••••••••••••-1••••••••••••••••••••••••••••••••1•••••••••••••••••••••1••••••••••1••••••••••
-----------------------------------•----------•----------1----------•----------I----------•--
PERSONS WITH NO DATA • 0 • 0 I O I O I O I
·-------•----------•-----------
O I I 0
• c o.o;o I ( o.o;o • 1 o.ox, I , o.ox, I I o.ox, I I o.o;o I • 1 o.ox,
0
0
,0
0
OD
-
Table l (Contd)
PATIENT COUNT CLINICAL tottPLAINTS
REC0118INANT HEPATITIS B VACCINE
STUDY OB54
TREATHENT
LOT tM"BER CK564
DOSE 10 HCG
PATIENT CLASS: CIIROUIC CAARIERS

•----------------------------------------------------------------------------•
• OAYS POST VACCINATION • NUtfflER
•----------------------------------------------------------------------------1
CLINICAL
COMPLAINTS • O • 1 • Z • 3 • 4
.......................................................................................... I 5
.......... I
, ,
WITH
,
.......... ICOMPLAIHTS
..........
-----------------------------------1----------l----------•----------l----------l----------l----------1----------l-----------
srsTENit I O I 1 I 1 I 1 I 1 I O I I l
IC o.o;o I I 50.07.) I I 50.07.I IC 50.07.). I 50.07.). C 0.07.1 I I I so.ox,
------------------------------------
RESPIRATORY I• O • 1 • 1 I 1 I 1 I O • • 1
• c 0.01.1 • c so.ox> • c so.or., I c so.or., I 1 50.01.1 • c o.or.1 I I I so.ox,
I I I I • I I •
PHARYNGITIS ISOAE TMROAT) I I
O 1 I 1 • l I 1 I O • I 1
• 1 0.01.1 I c 50.07.1 I I 50.07.> I c so.01.1 I 1 50.07.1 • I 0.0;:1 • I I so.o;:1
• I I • I • I I
ORGANS OF SPECIAL SENSE I O • 1 • 0 I O • 0 I O I • 1
• c 0.01.1 • 1 50.01.1 I 1 0.01.1 I I o.or.1 • 1 0.01.1 I I o.o;o • • 1 50.01.1
• I I • I I I I
EARACHE I O I 1 I 0 I 0 I 0 I 0 • • 1
I f 0.0¼) I I S0.07.) I ( 0.07.1 I I o.or., I I 0.07.I • ( 0.01.1 I • ( so.ox,
-----------------------------------1----------1----------•----------l----------l----------1----------I----------I-----------
PERSONS MITH COl1PLAJNTS I O I 1 • 1 • 1 • 1 • 0 • I 1
• I 0.07.1 • f 50.07.1 • I 50.07.1 • I 50.0XI I I 50.07.1 • C O.OXI • • f 50 . 07.1
-----------------------------------•----------•----------•--------·=•----------•----------•----------•----------•-----------
PERSONS WITH NO CONPUINTS • 2 I 1 • 1 I 1 • 1 • 2 • • 1
• 1100.or.1 • 1 50.01.1 • c 50.01.1 I I so.ox, I c so.01.1 I 1100.01.1 I • 1 so.ox,
-----------------------------------1----------l----------•----------l---------•----------l----------•----------•-----------
PERSONS WITH NO DATA • 0 I O • 0 I O I O I O I I 0
• I O.OY.l I< 0.07.1 • f 0.07.l I I 0.07.1 • I 0.07.1 • I O.OXI • I I O.OXI
0
0
.Q
-0
-0
.,,
Table 2
PATIENT COUNT HAXItt.Jt1 TEMPERATUIIES
AECOt'eINANT HEPAT I TIS B VACCINE
STUDY : 01154
TREATttEHT
LOT N\llt!ER Cl<564
005£ 10 HC6
PATIENT CLASS: CHRONIC CARRIERS
• · T0TAl VACCINEES I 18 PATIENTS) - DOSE l I

I•---------------------------------------------------------------------------------------1
DAYS POST VACCINATION I NUt18ER
HAX TEHPER ATUR£
(0[ G F, OR AL I I
•---------------------------------------------------------------------------------------1
O I 1 I 2 I 3 I it I 5 I I
MITH
• HA)( TEHP
••••••••••••••••••••••••• ..•••••••••••••••••••l..••••••••••••••••••••••••••••••l..••••••••••••••••••••-••••••••I••••••••••
I I • • I I I •
< 99 I 1s • 11 I 18 I 16 I 11 I 18 I I 12
I ( 83.3)0 I ( 94.4\)0 I (100.11)0 I ( 88.9)0 • ( 94.ltX) • (100 . 0X) • • ( 66. 7X )
I I I I • I I I
99 - 99.9 I 3 I 1 I I I z I o I o I I s
I , l6.7ZJ I , s .6XJ I , o.ox, I , 11.uo I , o.ox, I , a . ox, I I • Z7.8Y.J
I I I I I I I I
100 - 100 . 9 I I I e I e I o I 1 I o I • l
I l O.IXI I I D.DXI I ( D.DXJ I ( O.OXI I I 5.6XI I ( O.OXJ I I ( 5 . 6XI
------------------------1I----------1----------1----------l----------1----------1----------1---------------------1-----------
TEHPEA ATURE TAKEN 18 I 111 I 18 I 18 I 18 I 18 I I 18
I 1100.0XI I 1100.0XI I 1100.0XI I llDO.OXJ I 1100 . 0Y.I I 1100.0Y.I I I 1100.0X J
------------------------l----------l----------1----------1----------1----------l----------l---------------------l-----------
, EMPEAATUIIE NOT TAl<EN I O I o I O I O I o I o I I I
I • o.o:o I c a.ox, I , o.o;o I , o.ox1 I c o.o;o I , o.ox, • • c o.ex,
-
0
0
0
0
,
Table 2 (Contd)
PATIENT COUNT " AXIt1U'I TEHP£RAT~ES
RECOl18INANT HEPATITIS B VACCINE
STUOY 0854
TREATHEHT
l OT IU IBER CIC.56~
DOSE 10 HCG
PATIENT CU SS ·CHROIIIC CARRIERS
• TOTAL VACCINEES I 18 PATI ENTS! - 0051: 2 I

I•---------------------------------------------------·-----------------------------------1
OATS POST VACCINATION I tlU'18ER
HAX TEHPERATURE •--------------------------------------------------------------------- ------------------ • WITH
I DEG F, OR Al I • 0 • l • Z • . l • 4 I 5 • • • HAX TEHP
·························································•······················································•··········
I • I I • • • •
< 99 • 16 • 18 • 16 • 17 • 18 • 17 I • n
• ( 88,9)0 I (100.0)0 I C 88.91.) • C 9't.4l0 • (100.01.) I I 9't,41.J • • I 72,2i0
99 - 99,9
•• Z
I• O
•• 2
I• 1
I• 0
•
• l
•
•
I• 5
• I 11.11. ) • I 0. 01. J • I 11 . 11. I • I 5, 61. J • C 0. 01.1 • I 5. 61. J • • C 27. 8)0
------------------------1----------•----------l----------•----------
TEHPERATURE TAKEN I 18 I 18 I 18 • 18
•----------
I 18
I----------•---------------------•
I 18 I I '---------
18
• nao . 01.1 • n oo.o:o I noo.ou • noo . o;o • 1100.0:0 • 1100.0:0 • • 1100.0:0
------------------------
TEHPERATUl!E HOT TAKEN I•----------•----------•----------•----------•----------•----------1
O I O I O • 0 • 0 • 0 I ---------------------1
I -----------
0
I c o.o:o I I 0.01.1 I c 0.01.1 I c 0.01.1 I I 0.01.1 I I 0.01.1 I I C 0.01.1
-
0
-
0
--
Table 2 (Contd)
PATIEHT COUHT NAXll'tUH TEMPERATURES
AECotlBIHANT HEPATITIS 8 VACCINE
ST\JIJY 0854
TREATNEHT
LOT HUIBER Cl<564
DOSE 10 NCG
PATIENT CLASS: CHROHIC CARRIERS
I TOTAL VACCINEES C 18 PATIENTS) - OOSE 3 •

•---------------------------------------------------------------------------------------1
• DAYS POST VACClllATIDN • NnER
NAX TEMPERATURE
I DEG F, dRAL I •
•---------------------------------------------------------------------------------------•
0 I l I 2 • 3 • 4 • 5 • • • MAX TEl1P
MITH
..........................................................................................................................
< 99 •• JS •• 16 •• 15 I• 15 •• 17 •• 15 I• •• 9
• C 83.J7.I I C 88.9i0 I ( 83.37.l I C 83.3i0 • ( 94.4:0 I C 83.31.I • • I 50.0ZI
99 - 99.9
•I 3
II 2
II 2
II l
•• l
•• 3 I• •• 8
I I 16. 77.1 I I 11.17.l I I 11.17.1 I C 16. 7XI I C 5.6XI I c 16. 7XI I I I 44.47.l
• I I I I I I I
100 - 100.9 I o I o I 1 I o I o I D • I 1
I I O. OX I • I O. oz t I I S. 67.1 I I O. o:o I I D. 07.1 I I O. 07. l I I I S. 6X I
------------------------1----------•----------•----------l----------•----------l----------•---------------------I-----------
TEHPER l TURE TAKEN I ta I 18 I 18 I 18 I 18 I 18 • I 18
I ClOO.OZl • fl00.07.1 I ClOO.OXI I 1100.07.l I 1100.0Xl I ClOO.OXl I I 1100.0XI
------------------------1----------•----------•----------l----------•----------•----------•---------------------1-----------
tEttPERATUAE NOT TAKEN I O • 0 • 0 I O • 0 I O • I 0
I f o. o;o I I o. 07.1 I c o. ox i I I o. 07.1 • 1 o. 07.1 I c o. 07.1 I I I o. 07.1
-
0
0
0
rv
.,
Table 2 (Contd)
PATIENT COUNT HAXI~ TEMPERATURES
RECOttBINANT HEPATITIS B VACCIHE
STUOY 0854
TREATMEHT
LOT NUt18ER I Cl<564
DOSE 1 10 HCG
PATIENT CLASS: CHRONIC CARRIERS
• TOTAL VACCINEES I 18 PATIENTS)• DOSE 4 I

Il--------------------------------------------------------------------------------------1
DAYS POST VACCINATION I HUt18ER
HAX TEMPERAT~E
IDEGF,ORALJ
1------------------------------------•------------------------------·•·••---------------•
I I I l I 2 I 3 I 4 I 5 I I
NITH
IHAXTEMP
•••••••••••••••••••••••••••••••••••l•••••••••••••••••••••l•••••••••••••••••••••l••••••••••l•••••••••••••••••••••I••••••••••
I I I I I I I I
NORMAL I o I o I l I o I o I o I I o
1c o. o;o I c o • o;,., 1 1 s. 6;o I , o. o;,. 1 • , o. o;,., I , o. 07., 1 1, o. oz 1
I I • I I I I I
< 99 I 17 I 16 I 15 I 17 • 17 I 18 I • 1-.
I I 9't. lt7. t I C 88. 97. I • I 83. llO I c 9't. 4% I I I 94. 4% 1 I 11 oo. 07.) t I I 77. a;: I
I I I I I I I I
99 - 99.9 I l I 2 I Z I l I l I o I I It
I I S.67.) • ( 11.li(I I ( 11.17.1 I ( 5.67.1 I I 5.67.J I I o.o;o I I I 22.27.)
------------------------1---
TEHPERATURE TAKEN . I
·------l----------l----------l----------l----------l----------1---------------------1-----------
18 I 18 I 18 I 18 I 18 I 18 · I I 18
I 1100.ox1 I 1100.ox, I 1100.ox, I 1100.07.1 I 1100.07.1 I 1100.0Xl I I 1100.011
------------------------1----------1----------l----------l----------l----------l----------l---------------------l-----------
rEHPERATURE HOT TAKEN • 0 I 0 I O I 0 I D I O I I 0
I I o.o:o I I 0.07.J I I . o.ox, I c 0.07.1 I c 0.07.l I I 0.07.l I I ( 0.07.1
-
0
0
0
.....
.....
Table 2 (Contd)
PATIENT COUNT t1lXIt1U11 TEHPERATURES
RECot18IHlHT HEPATITIS 8 VACCINE
STUDY 085~
lREATt1ENT
LOT HUMBER Cti:56-.
OOSIE 10 HCG
I TOTAL VACCIHEES I 12 PATIEHnl - DOSES I

1---------------------------------------------------------------------------------------I
HAX TEHPERA~E
IDES F • ORAL I
1---------------------------------------------------------------------------------------I
I I I l I Z I 3 I 4 I 5 I I
MITH
I HAX TEMP
•••••••••••••••••••••••••••••••••••l••••••••••••••••••••••••••••••••l•••••••••••••••••••••l••••••••••l••••••••••I••••••••••
I
< 99 9 10 9 9 10 9 I 6
75.0ZI 83.31.) 75.01.) 1 s1.8::o 83.3%1 7s.o::o I I 50.07.1
I
z I
99 - 99.9 3
zs.o::o
l
8.3::0 16. T/.)
1
9.lJO
1
8.37.1
3
25.0iO I "
33.37.1
I
100 - 100.9 0 1 l l 0 o I l
0.01.) a.1::0 8.37.) 9.17.1 0.07.J O.OZJ I 8.3::0
I
101 - 101.9 o • o I o I o I 1 I o I I 1
, o.o;o I c o.oz1 I , o.o;o I I o.o;o I c a.Jio I I o.oz, I I I s.1z1
------------------------l----------l----------l----------1----------l----------l----------1---------------------l-----------
nt1PERATURE TAKEN I u I 12 I 12 I 11 I 12 I 12 I I 12
I 1100.oz> I 1100.oz1 I noo.oz1 I 1 91.7Z> I 1100.0::0 I noo.o::o • • uoo.o::o
------------------------l----------l----------l----------l----------l----------l----------l---------------------l-----------
TEt1PERATURE HOT TAKEN I o I 0 I o I l I 0 I o • I 0
I I o.OZI I I 0.07.1 I I o.oz1 I I 8.37.1 • c o.oz1 I I o.oz1 I • I o.o;o
-
0
0
0
J::,
~
Table 2 (Contd)
PATIENT CO\MT HAXINUtt TEHPERATUlES
STUDY l 085ft
TRUTHEHT
LOT tUIBER CK564
ODSE 10 HCG
PATIEHT CU SS: CHRONIC CARRIERS
I TOTAL VACCIHEES ( J PATIEHTSI - DOSE 6 I

1I ---------------------------------------------------------------------------------------I
DAYS POST VACCIHATIOH . I HUMBER
MAX TEHPERATUAE
I DEG F, Oll AU
1I---------------------------------------------------------------------------------------I
O I 1 I Z I l I It I 5 I I I HAW>< ITH
TEHP
······················••l••······••l••······••l••······••l•n••···••l••······••l••······••l••······••l••······••I••········
I I I I 1· I I I
< 99 I z I 2 I 2 I 2 I 2 I 2 I I z
I 1100.01.1 I 1100.01.1 I 1100.0ZI I 1100.01.1 I 1100.01.1 I 1100.DZI I I 1100.0Z I
------------------------ l----------
TEHPERATURE TAKEN I 2
l----------l----------l----------
I 2 I 2 I Z
l----------l----------1---------------------1-----------
I 2 I 2 I I 2
I c 66. no I c 66. 11. 1 I c 66. 71. , I c 66 •Tl. l I 1 66. 11.1 I « 66. 71., I I c 66 • 11. 1
------------------------1I ----------1
TENPERAT\JRE HOT TAKEN 1 I
----------
1
I----------
I 1
I----------
I 1
I----------I----------I---------------------
I 1 I 1 I
I-----------
I l
I c 33.31.1 I c JJ.31.1 I c 3l.3i0 I t 33.3XI I c 33.3Z I I c 33.31.1 I I c 33.31. l
...
0
c:,
Q
\J1
-
EFFICACY
01006
EFFICACY SUMMARY
Hepatitis B vaccine derived from the plasma of chronically infected

individuals was previously shown to be effective in preventing hepatitis B
infection among adult male homosexuals and staff members in dialysis units.
This vaccine also proved to be effective in preventing chronic hepatitis 8
infection among infants born to 11others who are positive for both HBsAg and
HSeAg.
The efficacy studies involving plasma-derived hepatitis B vaccine demonstrated
that the presence of anti-HBs equated with protection against hepatitis B.
Consequently, the high seroconvers1on rates observed for reciphnts of the
yeast recombinant hepatitis 8 vaccine (e.g. 96% of healthy adult vaccinees
develop anti-HBs titers of 11IU/11l ~10) suggest that these individuals should
be protected against hepatitis B. Ongoing 1n. vitro studies to demonstrate the
equivalence of antl-HBs raised to yeast recombinant hepatitis B vaccine and
plasma-derived hepatitis B vaccine are described in Appendix 1.
The feasibility of conducting efficacy studies of the yeast recombinant

hepatitis B vaccine in various populations was considered. Such studies are
reasonable only in populations known to experience relatively high rates of
infection. Control groups are also a problem. Since a proven preven~ive
therapy (plasma-derived hepatitis B vaccine) is now available in oost parts of
the world, it is no longer ethical to conduct a study with untreated
controls. In so111e instances. notably w1th infants of Asian mothers who are
positive for HBsAg and HBeAg, there have been very high rates of infection
documented among untreated indiv1dua ls, and it 1s reasonable to use these
rates as a basis for estimating protective efficacy in contemporary studles
lacking untreated controls. However, historical data on the incidence of
infection in various candidate adult population are no longer applicable.
Rates of hepatitis B infect·i on are probably declining among homosexuals. due
to changed sexual practices since the AIDS epidemic. The incidence of
hepatitis B infection has also been declining for a number of years in
dialysis units. We have concluded that an efficacy study of the yeast
recombinant hepatitis B vaccine in an adult population Is not feasible.
However, studies involving infants born to mothers who are carriers of the
hepatitis B virus are feasible.
Four studies have been initiated to evaluate the efficacy of yeast recombinant
hepatitis B vaccine in preventing chronic hepatitis B infection in infants
born to mothers who carry the virus:
Study Study Population/Regimen
862 Healthy infants born to mothers who are positive for HBsAg
and either positive or negative for HBeAg receive a single
0.5 ml injection of HBIG at birth following by 5 mcg doses
of yeast recombinant hepatitis 8 vaccine or 10 mcg doses of
plasma-derived hepatitis B vaccine at 0, 1, and 6 months.
The study is being conducted 1n Hong Kong.
32381/1
1/29/86
01007
Study Study Population/Regimen
864 Healthy infants born to mothers of As 1an descent, who are

positive for both HBsAg and HBeAg, receive a single 0.5 ml
injection of HBIG at birth following by 5 mcg doses of the
yeast recombinant hepatitis B vaccine at O (within the
first few days of birth), 1, and 6 110nths. The study is
being conducted 1n the United States.
878 Healthy infants born to mothers who are positive for both
HBsAg and HBeAg receive either a single 0.5 ml injection of
HBIG at birth followed by 5 mcg doses of the yeast
recombinant hepatitis B vaccine at O (within 12 hours of
birth), 1, and 6 110nths, or vaccine alone. The study is
being conducted in China.
892 Healthy infants born to mothers who are positive for both
HBsAg and HBeAg receiving yeast recombinant hepatitis 8
vaccine ( 5 or 10 mcg dose) or plasma-derived hepatitis B
vaccine (10 or 20 ,neg dose) at O (within 12 hours of
birth), 1, and 6 months. This study fs being conducted 1n
China.
A total of 412 infants have been enrolled to date in the four studies, 289 of
these in groups receiving the yeast recombinant hepatitis B vaccine.
Postvaccinatf on follow-up data are currently available from studies 862 and
864 only. Conments regarding efficacy w111 be restricted to infants of
mothers positive for both HBsAg and HBeAg who are receiving passive-active
prophylaxis (HBIG at birth plus 5 mcg doses of yeast recombinant hepatitis B
vaccine at O, 1, and 6 months). The numbers of 1nfants who have received the
first, second, and third injections of vaccine together with their antigen
status at various times are tabulated below:
Stud:ll 862 Studi 864 Both Studies

Number Vaccinated
First Injection 40 134 174

Second Injection 37 120 157
Third Injection 12 61 73
Stud~ 862 Stud~ 864 Both Studies

Proportion HBsAg Positive
Birth 4/40 4/134 8/174

3 Months 1/25 3/85 4/110
6 Months 0/12 1/47 1/59
9 Months 0/19 0/19
Eight (8) infants were positive for H8sAg at birth. Four (4) of the eight
have been tested at 3 1110nths and all were still positive for HBsAg. One of
these infants has been followed through 6 months, is still HBsAg positive, and
is now classified as a chronic carrier. The infants who are positive for
32381/2
1 /22/86
01008
HBsAg at birth may have been infected l!!. utero and such infections cannot be
prevented through postnatal vaccination. To date , there have been no
persistent infections appearing after birth. ·-
- - - ----· . . ----
The efficacy of HBIG and yeast recombinant vaccine in preventing chronic
hepatitis B infection may be estimated with the following formula :
Incidence of
infection in
% Efficacy "' 1- vaccinated X 100
Incidence of
infection in
unvacc 1nated
The single chronic carrier among the vaccinated infants followed for six
months represents an incidence of 1. 7%. A nu11ber of previous studies have
estimated the incidence of chronic infection among untreahd infants born to
Asian 1110thers positive for HBsAg and HBeAg at 60-92%. 1 - 10 In addition,
the investigators in Study 864 have recently obtained follow-up serology on 13
children born 1n the United States duri_ng the past several years to mothers
positive for HBsAg and HBeAg who did not receive HBIG or hepatitis B vaccine.
Nine of the 13 children (69.2J ) had become positive for HBsAg. This rate is
similar to those cited above and was used as our estimate for the 1nc1dence of
chronic infection in unvaccinated infants. Estimates of the efficacy of the
HBIG-yeast recombinant vaccine regimen at 6 and 9 months are tabulated below:
Study 862 Study 864/ Both Studies
Efficacy in a> ( I\ '.
6 Months 98
9 Months 100
No serious adverse experiences related to vaccine have been reported. These

data suggest that passi~e-active prophylaxis involving a single dose of HBI6
and three 5 mcg doses of yeast recombinant hepatitis B vaccine h safe and
will provide a high level of protection against chronic hepatitis B virus
infection.
32381/3
1 /22/86
01009
References:
1. Beasley. R.P .• Trepo. C., Stevens. C.E., et al.: The e Antigen and
Vertical Transmission of Hepatitis 8 Surface Antigen. ~- i. Epidemiol.
105:94-98. 1977.
2. Beasley, R.P., Lee, G. C-Y., Roan, C-H., et al.: Prevention of
Perinatally Trans,aitted Hepatitis 8 Virus Infections wUh Hepatitis B
Inmune Globulin and Hepatitis B Vaccine. Lancet 2:1099-1102, 1983.
3. Chung, W.K., Yoo, J.Y., Sun, H.S., et al.: Prevention of Perinatal
Trans111iss ion of Hepatitis 8 Virus: A C011p11r1son Between the Efficacy of
Passive and Passive-Active Inmunization in Korea. J. Infect. Dis.
151 :280-286, 1985. - -
4. Or. M. Kane, CDC, personal comnun1cation.
5. Lo, K.J., Tsai, Y.T., Lee, S.D., et al.: Combined Passive and Active
I11111unization for Interruption of Perinatal Trans111ssion of Hepatitis B
Virus in Taiwan (Abst.), In. Vyas, 6.N., Dienstag, J.L., and Hoofnagle,
J.H. (eds.), Viral Hepatitis and Liver Disease, Grune and Stratton.
Orlando, 1984. pp. 679-680.
6. 0on, C.J., Chan, L., Goh, K.T., et al.: Epide•iology of Viral Hepatitis
B in Singapore (Abst.), In Vyas, G.N., Dienstag, J.L., and Hoofnagle,
J.H. (eds.). !!.!:!.!. Hepatitis and Liver Disease, Grune and Stratton.
Orlando, 1984, p. 642.
7. Pongpipat, D., Suvatte, Y., and Assateerawatts, A.: Hepatitis B Innune

Globulin (HBIG): Efficacy 1n the Interrupt1on of Vertical Transmission
of Hepatitis 8 Virus (HBV) Carrier State. J. Med. Assoc. Thailand
66:49-53, 1983.
8. Sh1kata, T., Yano, M., Shiraki, K., et al.: Efficacy Trial of HBIG and
Hepatitis 8 Vaccine for the Prevention of Perinatal HBY Trans•hsion, In
Vyas, G.N., Dienstag, J.L., and Hoofnagle, J.H. (eds.), Viral Hepat1t1s
a~d Liver Disease, Grune and Stratton. Orlando, 1984, pp. 593-597.
9. Wong, V.C.W., Reesink, H.W., Reerink-Brongers, E.E., et al.: Prevention
of the HBsAg Carrier State in Newborn Infants of Mothers Who Are Chronic
carriers of HBsAg and HBeAg by Administration of Hepatitis B Vaccine and
Hepatitis-B Innunoglobulin. Lancet 1:921-926, 1984.
10. Xu, Z-Y., Liu, C-B., Franch, D.P., et al.: Prevention of Perinatal
Acquisition of Hepat1t1s 8 Virus Carriage us;ng Vaccine: Prtl llainary
Report of a Rand01111zed, Double-811nd Placebo-Controlled and COllll)arat1ve
Trial. Pediatrics. 76:713-718, 1985.
31671/3
1/10/86
01010
EFFICACY
Study 862 - Hong King - Or.£. K. Yeoh
The study population consists of two groups of healthy infants. Group l

includes infants born to mothers positive for HBsAg and HBeAg. The infants
receive HBIG at birth and then either 5 mcg injections of yeast recombinant
hepatitis B vaccine lot C-K734 or 10 mcg injections of plasma-derived vaccine
at 0, 1, and 6 1110nths. Group 2 includes infants born to mothers positive for
HBsAg and negative for HBeAg. These infants also receive HBIG at birth and
then either yeast recombinant or plasma-derived vaccine according to the same
dose and schedule as the infants in group 1. The initial injection of vaccine
is administered within 12 hours after birth.
Twenty-eight infants in group l (HBeAg positive mothers) have received one

dose of t1BIG and the first injection of plasma-derived vaccine. Twenty-seven
and eight of these infants have received the second and third injections of
vaccine, respectively. Forty infants in group 1 have received one dose of
HBIG and the first injection of yeast recombinant vaccine. Thirty-seven and
five of these participants have been administered the second and third
injections of vaccine, respectively.
At three months, 100% (19/19) of the infants (group 1) who received

plasma-derived vaccine and 100% (24/24) of the infants who received yeast
recombinant vaccine developed protective levels (mlU/ml ~10) of anti-HBs
(excludes infants HBsAg positive at birth).
Two infants (group 1) who received plasma-derived vaccine were HBsAg positive
at birth. Both infants were negative for HBsAg at one month of follow-up.
One infant. who was HBsAg negative at one and three months, tested HBsAg
positive at six months. Her serum was anti-HBc IgM negative. Four infants
who rece1ved yeast recombinant vaccine were HBsAg posit1 ve at birth. At one
month, two of these were negative for HBsAg and two of the infants remained
positive. Three _ month serology data ;s available for one of the HBsAg
positive infants. This subject remained positive at that time.
Eighty-five infants in group 2 (HBeAg negative mothers) have received one dose
of HBIG and the first injection of plasma-derived vaccine. Seventy-nine and
18 of these have received the second and third injections, respectively.
Seventy-five infants in group 2 have received one dose of HBIG and the first
injection of yeast recombinant vaccine. Seventy-three and 15 of these infants
have been adm1nistered the second and third injections, respectively.
At three months, 10~ (42/42) of the infants (group 2) who · received

plasma-derived vaccine · and 100% (41/41) of the infants who received yeast
recombinant vaccine developed protective levels (mIU/ml ~10) of anti-HBs
(excludes infants HBsAg positive at birth).
Two infants who received plasma-derived vaccine were HBsAg positive at birth.
They tested negative at one month. Another infant was positive for HBsAg at
one month. Additional serology data are not available for this
31611/1
01011
Study 862 - Hong King - Dr. E. K. Yeoh (Cont.)

infant. Three additional infants, who were negative for HBsAg at one and
three months, tested positive for HBsAg at six months. In two of these cases,
the six ' month sera were ant1-H8c IgM negative. All three infants sero-
converted for ant1-H8s by three months post-entry into the study.
Two infants (group 2) who received yeast recombinant vaccine were HBsAg
positive at birth. Both infants were negative at one month. An additional
infant, who was HBsAg negative at one and three months, tested HBsAg positive
at s1>c months. The six month seru11 was ant1-HBc IgM negative. The infant
seroconverted for anti-Hes by three months post-entry into the study.
Study 864 - New York. NY - Dr. C. Stevens

Healthy infants born to women of Asian descent who are positive for HBsAg and
HBeAg, are enrolled in Study 864. The study is designed to evaluate rates of
chronic hepatitis 8 antigene~ia in infants at extremely high risk of
infection. The infants are scheduled to receive one dose of HBIG within the
first few hours of birth. Yeast recombinant vaccine (5 mcg injections) lot
C-1(732 is administered within the first few days after birth and at one and
six months of age.
One hundred thirty-four infants have received one dose of HBIG and the f1 rst
injection of vaccine. One hundred twenty and 61 infants have been
administered the second and third injections of vaccine, respectively. All of
46 antigen negative infants followed for 6 months had developed anti-HBs
(S/N ~2 .1).
Four infants were positive for HBsAg at birth. One of these has been followed
for 1 month only and remains positive. Three of the infants have been
followed for at least 3 months and were still antigen positive. One of the
three has been followed for 6 months and is still positive.
No serious or alaming adverse experiences related to vaccine have been
reported. Vaccination and follow-up continues in progress.
Study 878 - China - Dr. T. Sun

Healthy infants, born to women who are positive for HBsAg and HBeAg, are
enrolled in Study 878. The first 30 infants entered in the study receive one
dose of HBIG and a 5 mcg injection of vaccine lot C-K564 at birth. Subsequent
5 mcg injections of vaccine are administered at one and six 110nths of age.
All additional infants enrolled in the study receive no HBIG at birth and 5
mcg 1nject1ons of vaccine according to the same schedule (0, 1 and 6 months).
31611/2
01012
Study 878 - China - Or. T. Sun {Cont.)
Thirty infants have received one dose of HBIG and their first 5 mcg injection
of vaccine. Serologic data are not yet available. There have been no reports
of serious or alarming adverse experiences related to vaccine. Vaccination
and follow-up continues in progress.
Study 892 - China - Dr. Z. H. Hu
The study population consists of healthy infants born to mothers who are
positive for HBsAg and HBeAg. The study is designed to cOR1pare the efficacy
of yeast recombinant vaccine and plasma-derived vaccine 1n preventing chronic
hepatitis B anttgenemia among infants at high risk for infection. Infants are
randomly assigned to receive either 5 mcg or 10 mcg injections of recombinant
vaccine lot C-IC.564 or 10 mcg or 20 mcg injections of plasma-derived vaccine
lot 0027L. All injections are administered w1th1n 12 hours after birth and at
one and six months of age.
Five infants have receive the fint injection of vaccine in each dose and
vaccine reg1111en. Serology data are not yet available. No serious adverse
experiences related to vaccine have been reported. Vaccination and fol low-up
continues 1n progress.
31611/3
l /10/86
Study 862
01013
PROGRA: Yeast Recombinant Hepat1t1s B Vaccine, Study 862
PURPOSE: To evaluate the efficacy of 5 mcg doses of the yeast

recombinant hepatitis B vaccine, as cong,ared with
10 mcg doses of plasraa derived· vaccine H-B-VAX. both
given in conjunction with HBIG at birth in preventing
chronic hepatitis B infection among:
1. Infants born to mothers positive for HBsAg and
HBeAg.
2. Infants born to .mothers positive for HBsAg and
Negative for HBeAg.
VACCINE: Yeast Recombinant Hepatitis 8 Vacc1ne

Lot 987/C-K734
H-B-VAX, Plasma Oer1ved Hepatitis 8 Vaccine
Lot 1032K
Lot 2455J·
Lot 0027L
Lot 1507J
Hep-8-Gannagee
Lot 0031L
Lot 1120K
PRI MAR Y E. K. Yeoh, M.D., B.S., M.R.C.P.

INVESTIGATOR: Consultant Physician
Medical ·A· Unit
Queen Elizabeth Hospital
Kowloon, Hong Kong
SECONDARY w. K. Chang, M.P., 8.S., F.R.C. Path.

INVESTIGATORS: Consultant M1crob1olog1st
Queen Mary Hospital
Hong Kong
Patricia Ip, M.B., B.S., M.R.C.P.
Consultant Ped1atr1c1an
United Christian Hospital
Kowloon, Hong Kong
32281/1
1/21/86
0101~
Study 862
SECONDARY Enid Chan, M.B., 8.S., F.R.C.O.G.

INVESTIGATORS: Consultant Obstetrician
(Contd) United Christian Hospital
Kowloon, Hong Kong
K. H. Chan, ~.8., B.s .• ~.R.C.P.
Consultant Pediatrician
Caritas ~edical Centre
Kowloon, Hong Kong
Charles Fung, ~.O., S.S., M.R.C.O.G.
Consultant Obstetrician
Car1tas Medical Cente.r
Kowloon, Hong Kong
STUDY LOCATION: United Christin Hospital

Hip Wo Street
Kowloon, Hong Kong
caritas Medical Centre
Wing Hong Street
Kowloon, Hong Kong
Queen Mary Hospital
Pokfulam Road
Hong Kong
DATE INITIATED: February, 1985
STUDY POPULATION: The 300 population consists of approximately 150

infants born to mothers who are positive for HBsAg and
HBeAg . and 150 infants born to mothers who are HBsAg
positive and HBeAg negative. Other cr1ter1a for
e11g1bi11ty of the infants include the following:
1) Birth weight ~2000 grams.
2) Apgar score ~7 (taken at 5 mins.)
3) Good hea 1th
32281/2
1/21/86
01015
Study 862
PROCEDURE: At the first prenatal visit, a blood specimen is

obtained from prospective mothers and assayed for
HBsAg. 01n2n who are detected to be positive for
HBsAg are recruited into the study. A second prenatal
blood specinten will be obtained froni women who wish to
pa rt i c i pate and assayed for HBsAg. A third b1ood
specimen will be obtained fr011 the women at
parturition and assayed for HBsAg and HBeAg. Eligible
infants born to HBsAg, HBeAg pos 1tive won1en ~111 be
randomized into Groups 1 and · 2. Infants of HBsAg
positive and HBeAg negative worten w1 ll be randomized
into Groups 3 and 4.
Infants in all four groups receive HBig and hepatitis
B vaccine within 12 hours after birth in different
sites (anterior thighs). The second and third doses
of vaccine are administered one and six 110nths after
birth. Infants in Groups 1 and 3 receive recombinant
vaccine (5 mcg) and those in Groups 2 and 4 recetved
plas111a-derived vaccine (10 11Cg).
Blood specimens are obtained ffrom the infants prior
to vaccination and 1, 3, 6, 9, 12, 18 and 24 1110nths
post initial injection. All specimens are assayed for
HBsAg, and ant 1-HBs. Ant 1-HBc h a1so tested 1n the
infants• sera at 18 months. A follow-up blood sample
1s also obtained from the 110ther at six months.
Assays are perfomed by W. K. Chang us ing RIA kits.
RESULTS: HEALTHY INFANTS

HEP-8-GAM~AGEE Lot ,0031L or 1120K at ti me 0
S IIICg Lot 987/C-K734 at 0, 1, and 6 IIIOnths
10 mcg H-B-VAX Lot #1032K, 2455J, 0027L or 1507J at 0,
1, and 6 months
A. HEALTHY INFANTS BORN TO HBsAg-POSITIVE and
HBeAg-POSITIVE MOTHERS
InJection No .
Dose Level _1_ .L 3
5 mcg Rec0fflb1nant 40 31 12
10 mcg Plasma 28 27 10
32281/3
1/21 /86
0101b
Study 862
RESULTS (Contd) 8. HEALTHY INFANTS BORN TO HBsAg-POSlTIVE, HBeAg-

NEGATIVE MOTHERS:
1. Nul'Rber Vaccinated:
Injection fllo.
Dose Level _1_ ..l,_ 3
5 mcg Recombinant 75 73 30
10 IIC9 Plasma 85 79 25
A. Healthy Infants Born to HBsAg-Positive and
HBeAg-Positfve Mothers
At three months. 100% (24/24) of the ·
infants who received yeast recombinant
vaccine and lOOS (19/1 9) of the infants
who received plasma-derived vaccine
developed protective levels (mIU/ml ~10)
of anti-HBs (excludes infants who were
HBsAg-positive at birth). Table l gives
the range of antibody titers observed at 1
and 3 months.
Four infants who received yeast
recombinant vaccine were HBsAg-positive at
birth. At one 110nth. two of these were
negative for HBsAg. Of the two who
rema 1ned posit 1ve for HBUg. one has been
followed through three months and has
remained positive at that t1111e.
Two infants who received plas11111-derived
vaccine were HBsAg-pos1tive at birth.
Both were negative for H8sAg at one onth.
One infant. who was negative for HBsAg at
one and three months became pos 1t he at
six months. The serum sa!lple at that time
was anti-HBc IgM-negattve.
Refer to Figure 1 for a sunnary of HBsAg
positivity in these infants.
\
32281/1,
1/21 /B6
01017
Study 862
RESULTS (Contd) B. Healthy Infants Born to HBsAg-Pos1t1ve.

HBeAg-Negative Mothers
At three months. 100% (41/41) of the
infants who received yeast recombinant
vaccine and 1001 (42/42) of those who
received plasma-derived vaccine developed
protective levels (mIU/ml ~10) of antt-HBs
(excluding infants HBsAg positive at
bi r-th). Table 2 gives the range of
antibody titers observed at 1 and 3 months.
Two infants who received yeast rec0flb1nant
vaccine were HBsAg-pos1t1ve at birth.
Both were negative at one month. An
additional infant, who was HBsAg-negative
at one and three months was HBsAg-positive
at six months. The six month serum was
anti-HBc IgM-negative. This infant
seroconverted for anti-HBs by three 110nths.
Two infants who received plas1111-derived
vaccine were HBsAg positive at birth.
Both were negative at one month. Another
infant tested positive for HBsAg at one
month. Additional serology is not yet
available for this infant. Three
additional infants , who were negative for
HBsAg at one and three 110nths, were
positive at six 110nths. In two of these,
the six month sera were anti-HBc
IgM-negat1ve. All three of these had
seroconverted for ant1-H8s at three months.
Figure 1 presents a su11111ary of HBsAg
positivity in these infants.
Currently, only a preliminary sunnary of
clinical complaint data 1s available. The
investigator has reported that there have been
no clinical complaints a110ng the recipients of
either vaccine other than one infant who had a
fever of 37.s•c on the day following the first
injection. This infant received yeast
recombinant vaccine.
322B1/5
l /21/86
01018
Figure
HBsAg Positive Infants in Study 862
X ------- 0 ------ 0
X ------ 0 ------ 0 0 ----- 0 ------- X

X ------- X X ------- 0
X ------- X ----- X X ------ 0
Birth l Month 3 Months 6 Months Birth 1 Month 3 Months 6 Months

Infants born to HBeAg Positive Infants born to HBeAg Positive
Mothers who Received Yeast Mothers who Received Plasma-Derived
Recombinant Vaccine Vaccine
0 ------ 0 ------ X
0 ----- 0 ----- X
0 ------- 0 ------ X
------- 0 - - - - 0 ---------x X
X ------- 0 X ------ 0
X ------ 0 ----- 0 X ------ 0 ~---- 0
Birth l Month 3 Months 6 Months Birth 1 Month 3 Months 6 Months

Infants born to HBeAg Negative Infants born to HBeAg Negative
Mothers who Received Yeast Mothers who Received Plasma-Derived
Recombinant Vaccine Vaccine
X = HBsAg positive
o = HBsAg negative
32461/1
1/23/86
OtOtQ
Table 1
Anti-HBs in HBsAg Negative Infants* Born to HBeAg Positive Mothers
Who Received Yeast Recombinant Vaccine
Infants Age Number % { Proj!orti on} Anti-HBs mlU/ml

at Testing Tested 2.1-10 11-49 50-99 ~_100
1 month 31 3.2 ( l /31) 96:i (30/31)
3 months 24 41. 7 (10/24) 41. 7 (10/24) 16.7 ( 4/24)
*Excludes four who were HSsAg positive at birth
Ant1-H8s in HBsAg Negative Infants* Born to HBeAg Pos1t1ve Mothers

Who Received Plasma-Derived Vaccine
Infants Age Number % {Prol!ortion} Ant;-Hes mIU/ml

at Testing Tested 2. l-10 11-49 50-99 :::,100
1 month 25 12.0 (3/25) ae~o c2212sJ

3 months 19 52.6 (10/19) 1s .e (3/19) 31.6 (6/19)
*Excludes two infants who were HBsAg positive at birth
32461/2
1 /23/86
01020
Table 2
Anti-HBs in HBsAg Negative Infants* Born to HBeAg Negative Mothers
Who Received Yeast Recombinant Vaccine
Infants Age Number % (Proportion) Anti-HBs mIU/ml

at Testing Tested 2.1-10 11-49 50-99 ~100
1 month 68 1.5 (1/68) 4.4 (3/68) 94.1 (64/68)
3 months 41 41.S (17/41) 36.6 (15/41) 21.9 (9/41)
*Excludes two who were HBsAg positive at birth
Anti-HBs in HBsAg Negative Infants* Born to HBeAg Negative Mothers

Who Received Plasma-Derived Vaccine
Infants Age Number % (Pro12ortion} Anti-HBs raIU/ml

at Testing Tested 2.1-10 11-49 50-99 ~100
l month 76 2.6 (2/76) 97.4 (74/76)
3 months 42 40.5 (17/42) 23. 8 (10/42) 35.7 (15/42)
*Excludes two infants who were HBsAg positive at birth
32461/3
1/23/86
Study 864
01021

Study 8&4
PURPOSE: This study is designed to evaluate rates of chronic

hepatith 8 antigenemia in infants at extremely high
risk of 'infection who are treated with a combination
of HBIG and yeast recombinant hepatitis B vaccine.

Lot# 985/C-K732 (5 mtg HBsAg/~1)
Hep-8-GAMMAGEE
Lot # 11201(
2745J
2660J
0031L
PRINCIPAL Cladd E. Stevens, M.O.

INV£STI6ATOR: The Lindsley F. Kimball Research Institute
SECONDARY Rita H. Fisher, M.D.

INVESTIGATORS: Chief of Neonatology
St. Vincent's Hospital
Myron Tong, M.O.
Director, Liver Research
Center
Huntington Memorial Hosp.
Pasadena, CA 91109
Pearl Toy, M.D.
San Francisco General Hosp.
San Francisco, CA 94110
STUDY New York University Hospital

LOCATIONS: 550 First Avenue
New York, NY 10016
Beekman Downtown Hospital-
New York Inf1nury
170 William Street
New York, NY 10038
23821/85/l
1/3/86
01022
Study 864
STUDY LOCATIONS: Huntington Memorial Hospital

(Contd) 100 Congress Street
Pasadena, CA 91105
French Hospital
532 W. College St.
Los Angeles, CA 90012
University of California S.F.
Medical Center
Parnassus Avenue
St. Kary 1 s Hospital Medical Center
450 Stanyan
Columbia Presbyterian Medical Center
622 West 168th Street
New York, NY
Saint Vincent's Hospital
153 West 11th Street
New York, NY 10011
California Hospital
1414 s. Hopr St.
Los Angeles, CA 90015
Garfield Hospital
150 Hampton
Monterey Park, CA 91754
San Francisco General Hospital
1001 Portrero Avenue
San Francisco. CA 94110
Santa Clara Valley Medical Center
751 South Bascom Avenue
San Jose, CA 95128
Highland General Hospital
1411 E. 31st Street
Oakland, CA 94553
Kaiser Foundation Hospital
2425 Geary Blvd.
23821/851/2
1/3/86
01023
Study 864
STUDY LOCATIONS: Children Hospital, S.F.

(Contd) 3700 Ca11forn1a St.
Contra Costa County Health Services
2500 Alhambra Avenue
Martinez, CA 94553
Kaiser Permanente Hospital
280 West MacArthur Blvd.
Oakland, CA 94611
DATE INITIATED: September· 1, 1984.
STUDY POPULATION: The study population consists of healthy infants (i.e.,

weigh~ 2000 gms at birth and have an apgar score~ 7
at 5 minutes) born to mothers of Asian descent who are
positive for both HBsAg and HBeAg. Enrollment of at
least 80 infants is planned.
STUDY PROCEDURE: Infants, whose parents consent to their enrollment t n

the study, receive a single intra11uscular injection of
HBIG (0. 5 cc) within the f1 rst few hours after b1rth.
Pregnant women of Asian descent are screened for
hepatitis infection prior to delivery to identify
potential study candidates within the first few hours
of birth (infants). The initial 1.0 ml ( 5 mcg HBsAg)
intramusc~lar injection of recombinant hepatitis B
vaccine 1s given in the first few days after birth.
The second injection of vaccine is ad11inistered at one
month of age, and the third injection is received at
sh months. If an infant becomes HBsAg positive prior
to completing the tnrnuntzatton schedule, no further
vaccine injections will be administered.
A cord blood specimen is obtained at the time of
delivery and just prior to administration of the HB16.
A venous blood sample is also to be taken from the
infant at this time. The cord sample is tested for
HBsAg and the venous sample for H6sAg and ALT (SGPT).
23B21/851/3
l /3/86
0102LI
Study 864
STUDY PROCEDURE: Follow-up venous blood samples are obtained from the
(Contd) infant at 1, 3, 6, 9, 12, and 18 months of age. These
sera are tested for HBsAg, antt-HBc, anti-HBs and
ALT. A follow-up blood sa11ple is also obtained from
the mother at or near the t1me of delivery to verify
her HBsAg and HBeAg positive status.
Sera are being tested l'b)t(~..) New Yorlc Blood Center by
radioi11111unoassay using kits. Some sera 11ay be
tested for yeast antibody at MSDRL.
RESULTS: INFANTS OF HBsAg+/HBeAg+ MOTHERS

5 mcg lot 985/C-K732 at 0, 1, and 6 months
Injection I
_1_ _L_ _L
134 120 61
Four infants were positive for HBsAg at birth.
One of these has been followed for 1 110nth only
and remains positive. Three of the infants have
been followed for at least 3 months and were
still antigen positive. One of the three has
been followed for 6 months and is still
positive. This infant is now classified as a
chronic carrier (Figure 1).
At present, only a preliminary sumary of
antibody response data is available. According
to the study investigator, all of 46 antigen
negative infants followed for 6 months had
developed anti-HBs (S/N ~2 .1). Refer to Table l
for ant1-HBs responses through 9 months of
follow-up.
23821/851/4
1/3/86
01025
Study 864
Currently, only a preliminary sunmary of clinical

complaint data is available. The study
investigator has reported the following overall
frequencies of complaints:
Type of Freguenc~ in J b~ Injection t

· CQ!!mlaint 1 2 3
:I Fever ~100°F 3.2 (3/95} 1. 3 (1/77) 9.7 (3/31)

/
i Loca 1 redness 2. 1 (2/95) 1. 3 {1/17) 19.4 (6/31)
or swelling
Rash 1. l ( 1/95) 5.2 (4/77) 3.2 ( 1 /31)

Other 3.2 (3/95) 2.6 (2/77) 0 (0/31)

Reactions Reported to the OoBRR:
A neonatal male received HBIG and his first injection

of vaccine at birth (b) 6) . On the fifth and sixth
days post-vaccination ne naa a temperature of 38°C.
The infant received Tylenol and his temperature
returned to nonnal. He received his second and third
injections of vaccine without temperature elevation.
neonate received l dose of HBIG at birth

He developed physiologic jaundice on day 4
after birth. The jaundice resolved by
day 7. The first injection of vaccine was
administered on (b) (6) The infant received the
second and third rnJec~1ons of vaccine without local
or systemic complaints.
on the first day of life, a female neonate had a fever

of 101. 7°F. The child received one dose of HBIG at
birth. The following day her temperature was nonnal
and she received her first injection of vaccine. Her
temperature remained within nonnal limits after the
first , second, or third injections of vaccine .
23821/851/5
1/6/86
0102&
Study 8£>4
RESULTS: (Contd) A male neonate was reported to have developed jaundice

during the post-natal period. He had received one
dose of HBIG at birth (b) (6) and his first
injection of vaccine three aays later. The second
injection of vaccine was administered on (b) (6)
There has been one death among study participants
unrelated to vaccine.
A one-day old full tern male infant with Apgar scores
of 9 at both l and 5 minutes was entered into the
study. He received one dose of Hep-8-Ganmagee on the
day of birth and his first dose of vaccine on the
following day. The infant did well until 2 days post
delivery when poor feeding was noted. A cardiac
evaluation revealed a murmur and possible atrial
septal defect. His clinical condition deteriorated
requiring intubation and administration of pressor and
diuretic agents. The infant died 7 days after birth
after circulatory collapse and the onset of
arrhythmias. An autopsy revealed intracranial, renal
and hepatic hemorrhage. hypoplasia of the left auricle
and ventricle, a patent foramen ovale, an atrial
septal defect, and aspiration pneumonia.
23821/851/6
l /6/86
01027
Figure l
HBsAg Pos1t1ve Infants 1n Study 864
0 --------- X --- ----- 0
X --------- X
X --------- X -------- X
X --------- X -------- X
X --------- X -------- X --------- X
Birth l 14onth 3 Months 6 Months
X-= HBsAg+
O-= HBsAg-
23821/10
1/23/86
01028
Table l
Yeast Recombinant Hepatitis B Vaccine in

Perinatal Transmission: Anti-HBs Response in HBsAg Negative Infants
Study 864
Infant's Age Number %Anti-HBs (Titer 1n S/N)

at Testing Tested 2.1-19.9 20-49.9 ~50
3 Months 82 36 43 21
6 Months 46 7 29 64
9 Months 19 0 16 84
wva/23821/8
1/13/86
Study 878
Study 878
PURPOSE: To evaluate the efficacy of yeast recombinant

hepatitis B vaccine, given in conjunction with
hepatitis B immune globulin at birth, or alone, in
preventing chronic hepatitis B infection among infants
born to mothers positive for HBsAG and HBeAg.

I~MUNE GLOBULIN: Hepatitis B Immune Globulin

HEP-8-GAMMAGH
Lot 0031L
PRIMARY Sun Tsung-tang, 14.D.

INVESTIGATOR: Chainnan, Department of I11111unology
Cancer Institute (Hospital)
Chinese Academy of Medical Sciences
Panjiaynan, Beijing
People's Republic of China
SECONDARY Dr. Chu Yuan Yun

INVESTIGATOR: Qidong Liver Institute
Qidong
STUDY LOCATION: Qidong Liver Institute

Qidong, Jiangsu Province
DATE STUDY INITIATED: July, 1985
STUDY POPULATION: The study population consists of 70-150 healthy

infants born to mothers who are posit;ve for HBsAg and
HBeAg.
32111/1
1 /17/86
01030
Study 878
STUDY PROCEDURE: Prior to enrollment of an infant in this study, a

prenatal blood sample is obtained from each
prospective mother. A follow-up blood sample is also
obtained from the mother at the time of delivery to
verify the eligibility of infants for the study.
Eligible infants receive a single 0.5 ml intramuscular
injecton of hepatitis 8 1nmune globulin in the
anterior thigh within 12 hours of birth, followed by a
0.5 ml (5 mcg HBsAg) intramuscular injection of yeast
recombinant hepatitis B vaccine in the contralateral
anterior thigh at O (within 12 hours of birth), l and
6 months, or vaccine alone according to the same
regimen.
The parent or guardian wi 11 be asked to record the
child's temperature and any local or systemic
complaints for f,ive days after each injection of
vaccine.
A blood sample is obtained from each infant prior to
vaccination and, 1f possible, at 3, 6, 12, and 24
months.
All serum samples obtained from each mother are
assayed for HBsAg, anti-HBs, anti-HBc, and ALT.
All serum samples obtained from each infant are
assayed for HBsAg, anti-HBs, and when indicated for
ant 1-HBc and Al T. Samp 1es may be tested for yeast
~25 mlU/ml may be tested to determine anti-~ and
anti-~ subtype specificity.
RESULTS: To date, 20 infants have received one injection of

vaccine in conjunction with HBIG. No serious or
alaming reactions attributable to vaccination · have
been reported. Clinical follow-up data and serologic
results are not yet available. The study continues in
progress.
3211 I/2
l /17/86
Study 892
01032
PROGRAfJl: Alum-Adsorbed Yeast Recombinant Hepatitis B Vaccine,

Study 892
PURPOSE: To compare the efficacy of yeast recombinant hepatitis

B vaccine and plasma-derived hepatitis B vaccine 1n
preventing ~hronic hepatitis B infection among infants
born to mothers positive for HBsAg and for HBeAg.
VACCINE: l. Yeast Recombinant Hepatitis B Vaccine

Lot 81954I/18071/C-l220 (10 mc:g HBsAg/ml)
Lot 0027l (20 mcg HBsAg/ml)
PRIMARY Or. Hu Zong-Han

INVESTIGATOR: Department of Biological Products Inspection
Bureau of Pharmaceutical and B1olog1cal Inspection
~inistry of Health
SECONDARY Dr. Meng Lingxian

· INVESTIGATOR:
STUDY LOCATIONS: The Third Hospital

Shen Yang Municipal Anti-Epidemic Station·
Fujian Provincial Anti-Epidemic Station
Fujian, People's Republic of China
Guang Dong Provincial Anti-Epidemic Station
Guang Dong, People's Republic of China
Si Chuan Provincial Anti~Epidemic Station
S1 Chaun, People's Republic of China
32061/1
1/16/86
01032
Study 892
STUDY POPULATION: The study population consists of 200 healthy infants of

either sex, born to mothers who are positive for HBsAg
and for HBeAg.
STUDY PROCEDURE: Prior to enrollment of an infant 1n this study, a

prenatal blood sample 1s obtained from each prospective
mother. A follow-up blood sample is also obtained from
the mother at the time of delivery to verify the
eligibility of infants for the study.
Infants are randomly assigned to receive yeast
recombinant or plasma-derived hepatitis B vaccine as
fo 1lows:
Grou Vaccine Dose Number Re imen

l Recombinant 5 mcg so 0.5 ml 1ntramuscula
injectfon of vacc1n
within 12 hours of birt
and at 1 and 6 months
10 mcg 50 1.0 ml 1ntramuscula
injection of vaccin
and at l and 6 months
2 Plasma 10 mcg 50 0.5 ml 1ntramuscu 1a
injection of vaccin
and at l and 6 months
20 mcg 50 1.o ml intramuscula
injection of vaccin
and at 1 and 6 months
The parent or guardian wi 11 be asked to record the

child's temperature and any loca 1 or systemic
complaints for five days after each injection of
vaccine.
A blood sample is obtained from each infant prior to
vaccination and at 1, 3, 6, 7 or 8, 12, and 24 months
of age.
32061/2
1/16/86
01033
Study 892
STUDY PROCEDURE: All serum samples obtained from each mother are
(Contd) assayed for HBsAg, HBeAg, anti-HBe and ALT.
A11 seruli samples · obtained from each infant are
assayed for HBsAg and anti-HBs, and when indicated for
anti-HBC and ALT.
RESULTS: To date, 20 infants have received one injection of

yeast recombinant or plasm-derived hepatitis B
vaccine. No serious or alarming reactions
attr ibutable to vaccination have been reported.
Clinical follow-up data and serologic results are not
32061/3
1/16/86
01033-A
APPENDIX 1
EQIVALENCE OF ANTIBODY RAISED TO YEAST RECOMBINANT HEPATITIS B VACCINE
AND TO PLASMA-DERIVED HEPATITIS 8 VACCINE
46071/1
01033-8
Antibodies and Protective Efficacy
Clinical studies with the plasma-derived vaccine established the relationship

between antibody to the hepatitis B surface antigen (anti-HBs) and protection
against hepatitis 8 infection.
To support the protective efficacy studies that have bP.en done in chimpanzees
(with yeast-derived hepatitis B vaccine) and those ongoing in neonates.
serological studies designed to demonstrate the equivalence of anti-HBs
antibodies raised to yeast-derived hepatitis B vaccine and to plasma-derived
hepatitis 8 vaccine are being carried out.
These are:
A. Cross-Adsorption of Antibodies Raised to Plasma-Derived Vaccine and
to Yeast-Derived Vaccine
(o) (~) assays D) (4) showed that anti-HBs raised in plasma
vaccinees completely reacted with yeast-derived vaccine antigen and,
conversely, antibodies raised to the yeast-derived vaccine were
completely cross-reactive with plasma-derived vaccine antigen (see
Table l}. This demonstrates that both vaccines raise essentially
identical antibodies. Had either vaccine raised substantially
different antibodies, incomp1ete cross-reactivity would have been
observed with the converse antigens. This did not occur.
B. Binding of Anti-HBs to Synthetic Peptide (affinity constants)*
An important convnon ant1bo · · · in_ rec_ipi ents of bo h
1
vaccines as demonstrated b.>1 (b) (4)
(b)(4) (an important amino c'1 sequence rn 110s1\91. oino,ng or
this antibod to this peotide can be used to derive affinity.__ _....,
i:.on~t~nt~ hv (D) (4)
(b) (4)
_i_ll be noted that the
Affinity constants are shown in Table _2___ J_t _w
average affinity constant for antibodies induced in plasm, vaccinees
is 4 X 10 and that in the yeast vaccinees is also 4 X 10.
* Affinity constant defines the binding strength of the antibody to
its respective antigen.
C. Inhibition Assay with "Protective" Monoclonal anti-HBs Antibody
Usjna the "protective" monoclonal antibody (15) ~)
(b) (4) in an inhibition assay. the presence ot antibod, es to the
identical HBsAg epitope can be detected and quantitated in the sera
of plasma and yeast vaccinees (see Table 3). It has been clearly
shown that recipients of our plasma and yeast hepatitis B vaccines
make such antibodies in equivalent amounts.
01033-C
D. Avidity Constants
If the assay described under Affinity Constants is used with the
entire hepatitis B surface antigen against sera from plasma and
yeast vaccinees, a property can be derived which is called the
avidity constant (see Table 4). The similarity of these constants
for the anti-HBs antibodies in plasma and yeast vaccinees further
demonstrates the qualitative similarity of antibodies elicited in
recipients of both vaccines.
E. IgM/lgG Antibody Pattern
Comparisons of IgM and IgG anti-HBs in plasma and yeast vaccinees
revealed similar patterns; i.e., initial production of IgM anti-HBs
changes over to IgG anti-HBs as the vaccination regimen progresses
in recipients of each vaccine (see Table 5).
F. 0 Antibody. A Antibody Pattern
The plasma and yeast vaccinees sera show similar patterns with
respect to the formation of antibody specific for the subtype
determinants of HBsAg (type ad HBsAg used as inmunogen). D antibody
is initially high and as the vaccine regimen progresses, this
converts to A antibody and is nearly 100% A at the completion of the
3-dose regimen (see Table 6). (A is the broadly reactive and
protective antibody in anti-HBs.] ·
01033-D
TABLE 1
CROSS NBJTAALIZATION OF ANTIBODIES
%NEUTAALIZATION WITH
YEAST HBsAB (Q934) (b) (4) AY Pl.ASMA fID Pl.ASMA AD YEAST
( 6) (6) (4 /"OS I ) 98 100 100
(4 MJS,) 98 100 100
(4 M'.:JS,) 98 100 9Y
(4 MJS,) 94 100 99
(4 11JS,) 97 100 99
(4 t1:>S,) 87 100 100
PlASt-4A HBsAs (6) Pl) %NEUTRALIZATION WITH

~ LOT 820} AY Pl.ASMA AD Pl.A~ AD YEAST
-(b) (6)C3 r-os. J 86 100 99
(3 t-'OS,) 97 99 95
(3 t-'OS,) 94 100 97
(3 r-os. > 50 100 93
(3 r,os,) 86 100 97
(3 r,os. > 87 100 87
ASSAYS PERFORMED tT MSDRL BY W. MILLER ET AL.

I - -
01033-E
TABLE 2
AFFINITY COOSTANTS OF HBsAB IN HlJ1"1ANS RECEIVING

REca13INANT OR PLAS1i\ DERIVED VACCINE
01 033-F
TABLE 3
INHIBITIOO OF THE PROTECTIVE Ml«LONAL HBsAs BY Hl.JMd.N

HBsAB FIU-1 P.ECCJ't1BINANT OR PLASMl\-DERIVED VACCINE
PLAsKc\ VACCINEES
% INHIBITION
SbMPLE (b) (4) (o) (4) MSDRL
(b) (6) 19 17
18
46 --
77 74
97
23
38
99
--
97
37
86 79
YEAST VACCINEES
~ ,.,. , JM-IIBITION
SN-1PLE
(b) (4) (6) (4) MSDRL
(6) (6) 66
19
59
--
14 18
65
13
38
--
4lj
68
13
10
--8
69
83
79
77
81
(6) (4)
----- -----
01033-6
TABLE 4
AVIDITY C:CWSTANTS OF HBsAB

YEAST RECCY-1BINANT HBS VACCINEES
BLEEDING NuMBER
16) (6) (4 t-DS,)
(b) (4) AVID11Y lDlSTANT
LI X 10lO
(4 t-0S,) 1 X 10lO
(4 t-0S,) 16 X 1oJO
{4 t-0S,) 5 X 1010
(4 11)$,) l X 10lO
(4 11)S,) 14 X 10lO
PLASM!), DERIVED H8s VACClNEES

BLEEDING Nt..MBER
(b) (6)c3 r-os,l (b) (4) AVIDl1Y CoNSTANT
4 X1010
(3 11)S,) 8 X 101D
(3 r-os,) 4 X1010
(3 f,'()S,) 4 X10lO
(31'()S,) 7 X 1010
(3 f,'()S,) 8 X 10.l0
ASSAYS PERFORMED AT MSDRL BY W. MILLER ET AL.

01033-H
TABLE 5
RELATIVE ProFORTIONS Cf(b) (4) ANfl-HBS IN SERLM

PERCENT OF TOTAU(~) ~ 4 )
STUDY CASE "TYPE* '1JNTHS POST INITIAL VACCINATION
PRE l 2 3 4 Q
(b) (6) (b) (4)
779 0 100 0
0 0 100
(YEAST)
0 25 0
.0 75 100
0 0 0
0 100 100
0 0
0 100
0 100 1
0 0 99
542 0 0 4
0 100 96
(PLASMA)
0 "51 0
0 63 100
0 8 12
0 ~ 88
639 0 0 0
(PLASMA) 0 100 100
0 0 0
0 100 100
ASSAY
(b) (4) (b) (4)
01033-1
TABLE 6
PERCEITTAGES OF ANTI-HBS SPECIFIC FOR h AND Q DET'ffi"1INAITTS

OF HBsAG IN POST-VACCINATION SERA
YEAST VACCINEES
• M:>Nnis AFTER ltJMBER OF %ANTI-A %ANTI-D
FIRST INJECTION SAMf>LES RANGE f EAN RANGE !¥AN
1 20 0-100 65 0-100 34
3 69 33-100 91 0-63 9
6 44 58-100 93 0-37 7
7 2.7 81-100 95 0-19 5
8 12 94-100 97 0-6 3
PLAS-\4 VACCiteS
1-bNTHs AFTER ltJMBER OF %ANTI-A %ANTI-D
FIRST INJECTION SAMPLES RANGE fbj.j RANGE ft'EAN
1 0
3 3 87-89 88 9-13 12
6 6 79-95 89 5-18 10
7 8 74-97 93 2-26 7
12 7 87-96 9L! L!-13 6
ASSAYS PERFORMED AT MSDRL !Y W. MILLER !!_!1_. ( ) (4 METHOD lbl t4 l

'--
(b)(4)
REFEREtlCES
01031.1
REFERENCES
Butterly L, Watk ins E. Hinkle CH, Oienstag Jl. Response to recombinant yeast
hepatitis 8 vaccine in nonresponders to plasma-der ived hepatitis B
vaccine. Hepatology 1985; 5:1007 (Abstract).
Dandolos E, Roumeltotou-Karayannis A, Richardson SC , Papaevangelou G. Safety
and inrmunogenicity of a recombinant hepatitis B vaccine. J ~ed Virology
1985; 17:57-62.
Davidson M, KrugrBan S. I111711Unogenicity of recombinant yeast hepatitis B vaccine.

Lancet 1985; 1:108-9.
Davidson ~. Krugman S. RecOfllbinant yeast hepatitis B vaccine : Side effects
and i111111Unogenicity compared ~1th plas111-dtrivtd hepatitis B vaccine.
Subfllitted for publication to Hep&titis Scientific Nenioranda.
Deinhardt F. J11g w, Zoulek G. Lorbeer B, Wi lske 8. Clinical evaluation of a
recOlllbinant hepatitis B vaccine. In: Vyu GN, Dienstag Jl , Hoofnagle
JH, eds. Viral Hepatitis and Liver Disease. Orlando:Grune and Stratton,
1984:699 (Abstract).
D1enstag JL, watkins E, Hinkle CA. Recombinant yeast hepatitis B vaccine:
innunogen1c1ty and safety. Hepatoloqy 1984; 4:1077 (Abstract).
Oienstag JL, watkins E, Hinkle CA. Safety and i11111Unogentcity of a recombinant
hepattt1s B vaccine (Abstract). In: Vyas Gt4, Oienstag JL, Hoofnagle JH,
eds. Viral Hepatitis and liver Disease. Orlando:Grune and Stratton,
1984:710.
Heijtink RA. Kruintng J, Bakker M, Schalm SW. lanune response after vaccination
\11th recombinant hepatitis B vaccine as COfllPared to that after
plas111B-derived vaccine. Antiviral Res 1985; Suppl. 1:273-9.
Heijtink RA. Schalm SW. Ant1-H8s/a detena1nat1on after hepat itis B vaccination.
Submitted for publication to Lancet 1985.
Hille111n MR. Buynak ER, Markus HZ, Ma igetter RZ, NcA leer WJ. Mclean AA, et.al.
Control of Hepatitis B virus infection: Vaccines produced frOfil Alexander
cell line and from recOllbinant yeast cell cultures . In: Vyas GN, D1enstag
JL. Hoofnagle JH, eds . Viral Hepatitis and Live r Disease. Orlando:Grune
and Stratton. 1984:307-14.
Hillenian HR, Wl!ibel RE. Seolnick EN. RecOllbinant yeas t hu111n hepatitis B
vaccine. J Hong Kong Med Assoc 1985; 2:75-85.
Hollinger FB, Sanchez Y, Troisi C, Dreesm n GR, Meln ick JL. Iaunogenicity
and reactogenicity of nfN hepatitis B vaccines. Hepatology 1984;
4:1027(Abstract).
Hollinger FB, Troisi CL., Pepe PE. Antt-HBs responses to vaccination ~1th a
hUIRln hepatitis B vaccine lllide by recontbinant D~A technology in yeast. J
Infect Dis 1986; 1:156-9.
01035
J1lg W, Schmidt~. Zoulek G, Lorbeer B, ~11ske B. Deinhardt f. Clinical

evaluation of a recombinant hepatitis B vaccine. Lancet 1984; 2:1174-5.
J11g ~. Zoulek G. Lorbeer B, Wilske B, Deinhardt F. Clinical comparison of a
recollbinant and a plas111B-derived hepatitis B Vaccine (Abstract).
Presented at the 2~th Intersc1ence conference on antimicrobial agents and
chetm:>therapy, ~shington, OC, October 1984
cAleer WJ, 8uynak EB, '4aigetter RZ, ldampler OE, Miller ~J, H11lentin R.
Hu111an hepatitis 8 vaccine from reconibinant yeast. ~ature 1984; 307:178-80.
ueller R, B r J, Braas H, Deinhardt A, J1lg , Kuttler G, et al. Erste
erfahrungen m1t rekomb1nanter hepatitis a-vaccine be1 pat1enten unter
chron1scher haemod1alyse-behandlung. Gastroenterol 1985: 23:297.
Papaevangelou G, Dandolos E, Ro~11otou-Karay&nnis A, Richardson SC.
Inunogenic1ty of recombinant hepatitis B vaccine. Lancet -1985; 1:455-6 . .
Scolnick EM, clean AA, West DJ, Dienstag JL, wattins E, Deinhardt F, J1lg w.
Antibody and clinical responses among healthy adults to a hepatitis B
vaccine 111ade by recombinant ONA. In: Vyas GN, D1enstag JL, Hoofnagle JH,
eds. Viral Hepatitis and liver Disease. Orlando:Grune and Stratton. 1984;
315-17.
Scolnick EM, McLean AA, West OJ, ~cAleer WJ, ~11ler WJ, Buynak EB. C11n1ca1
evaluation in healthy adults of a hepatitis B vaccine made by recOftlbinant
ONA. JAMA 1984; 251:2812-15.
Zajac BA. West DJ, McAleer WJ, Scolnick EM. Overview of clinical studies with
hepat1t1s B vaccine (recombinant). Presented at the fifth biennial
scientific 11eeting, Asian Pacific Association for the Study of the Liver,
Symposium on recent advances in the prevention of hepatttts 8 infection,
January 1986 (Singapore).
24091-2
1/6/86
0103b
244 RE:S?ONSE: TO R!C~..BINA.t,:T YEAST H:::PATITIS B VACCrtn: IN

NO~RES?O!JDERS TO ~I.>.SM>.-OERIV::D HEPATITIS B VACCINE
L Butterlv, E Watkins, CA Hinkle and JL Dienstaq.
Castroin:estinal Unit, Massachusetts General Hospit~l,
'Soston, MA.
Preli.=lina:y reports suggested tti..~ recOlllbinant yeast
hepatitis B vaccine (R-?.Bvac) might be 110re iamunogenie
t..han the triply inactivated plasma-derived hepatitis B
vaccine (?-!-!!!vac) (Hepatology 1984:4:1077). Therefore,
to test this hypothesis, ve acministered three 10 ~g doses
of P.-H:3vac (Merck Sharp, Oohrne ~esearch Laboratories) at
time 0, 1, and 6 months to 14 normal adults ~ho had failed
to respond to one or 1110re courses (3-6 doses) of P-KBvac.
The frequency(; positive/C vaccinated] (,) and geometric
me~n titer (mIU/mll of anti-P.Bs responses vere as follows:
Month l 2 3 6
anti-;HBs+ 5/13 (39) 8/1 ◄ (5 7) 7 /1<1 (SO) 7/13 (54)
GMT ! SD 17 ! 7 39 ! 10 36 ! 23 8 ! 7
For comparison, the s&me data are charted belov for 65

seronegative health workers, never previously vaccinated,
after receiving R-HBvac:
Month 1 2 3 6
a.nti-HBs+ 26/65 (38) 53/62 (86) 61/65 (94) 60/62 (97i
G~ ! SO 7 ± 4 38 ! 4 so! 4 72 ! 4
The mean! SD a9es of the 8 initial nonresponders vho

ultimately did respond and the 6 who did not vere indis-
tinguish&.ble, JS t 8 and 41 ! 15. The response to R-HBvac
in almost 60, of nonresponders to P-HBvac appeared
prom.isinq, espcci&lly v~en compared vith a 40 \ rate of
low-level, poorly sustained anti-HBs responses in P-HBvac
nonresponders given a second course of P-HBvac
(Hepatolocrr 19S ◄ ;<l:1077); however, the level of
an~ibody fell substantially by six a,onths, vhen measured
just prior to the booster injection. Additional follow-up
will be necessary to detel"llline whether the antibody
response to R-HBvac in nonresponders to P-~Bvac increases
and is sustained after booster 1-unization.
Butterly L, Watkins E, Hinkle . CH, Dienstag JL. Response to recombi-

nant hepatitis B vaccine in nonresponders to plasma-derived
hepatitis B vaccine. Hepatology 1985; 5:1007 (abstract).
01037
Journal of MNlical Virology 17:57:-62 (19115)
Safety and lmmunogenicity of a

E. Dandolom, A. Roumellotou-Karayannls , S.C. Rlch1rdson, and
G. Papa vangelou
National Centre for Viral Hepatitis, Athens School of Hygiene, Athens, Greece
A hepatitis B vaccine produced in yeast by recombinant DNA technology was

cvaluaicd using 5-µg and 10-µg doses in a randomized trial lasting 7 months in
110 male anncd forces rccNits aged 17-19 year... Resulu were compared to those
· · of an identical trial of a plasma-<lcrived vaccine. No allergic reactions were
observed, and &he rate of m~d side cffecu was similar to the plasma-Gerived
vaccine. Scroconvcrsion rares in &he first month were 60'1, (33/5.5) and 67S (37/
55) with the 5-µg and 10-µg doses of lhc recombinant vaccine, respectively. A.Ii
panicipants seroconvcned by 3 mondis. and none lOSI antibody. These ~ulu are
very similar to those for plasma-derived vaccine. Comparison of iitr'C$ of antibody
10 hepatitis B surface antigen (anti-HBs) showed a slighuy higher level with the
10-µg than with the 5-µg dose of chc recombinant vaccine. Cieomctric mean ti!J'C$
of anti-HBs after the booster dose were similar in the S•p.& and 10-µg dose
recombinant vaccine groups (2,620 and 2,748 IU/1, respectively) and in the 5-µg
plasma-derived vaccine Jl'OUP (3,.591 IU/1) but significandy higher (9,227 IU/1)
with the 10-pg dose of the plasma-derived vaccine. These results confirm the
safciy and irnrnunogenicity of the recombinant vaccine, although funher study i5
needed on the duration of immunity.
K~y -Nb: activ~ lmmunoprop)lylaxis, hqialltis B, plasm■ -ikrived hrpatltis B v■ttine, ncombi-
1aat hepatitis B raceme
INTRODUCTION
The safety and immunogcnicity of plasma-derived hepatitis B vaccines have
been amply demonstrated by clinical trials in various high-risk groups in different
pans of the world [Szmuness Cl al, 1980; Maupas et at. 1981: Beasley el al·, 1983].
However, the high cost and limited availability have prevented widespread use of
these vaccines, especially in the less developed areas where they are needed most.
Vaccination programmes are at present generally limited to groups at high risk of
infection, such as hospital pcrsoMel. Within thc:sc programmes, acceptance may have
been affected by unfounded loss or confidence in the safety or the vaccine, following
Acccp1cd for publiwion April I. 1985.
Adcllcu reprinc miuau 10 Prof. G. PapGtvangelou, NatioMl Centre for Viral Hepatitis. Alhcns School
of Hniene, P.O. Bo1t 1.085 . Alhem 115 21. Greece.
© 1905 Alan R. Lia, IAc.

01038
Rtcombi11&11t Hepatitis B Veccine - S9
isons at each time point. AJI analyses were carried out after logarithmic transforma-
tion of anti-HBs titres.
RESULTS
The trial was completed in all but two recruits, both the losses being from the
group receiving the 10-,ig dose. One was lost from the study after receiving the
second dose and the other after the booster dose. No participant developed either
clinical or asymptomatic viral hepatitis, and neither anaphylactoid nor other allergic
reactions were observed. Mild side effects were reported, but no case of fever above
37.5°C wu noted, and no local discomfort or pain lasting for more than 1 day. The
overall frequency of side effccu was very similar to that reported for the plasma-
derived vaccine in the earlier study (fable I).
The rwo groups receiving recombinant vaccine showed a similar and rapid
immune response (Table m. Both of the recruits who did not complete follow-up had
already seroconvened in the first month. All participants had scroconvened by 3
months, and none lost antibody. These rates are very similar to those recorded in the
trial of the plasma-derived vaccine. Differences in seroconvcrsion rates at I month
between the four groups in Table II are not significant (x1 • 5.26; P • 0.15).
Geometric mean titres (GMT) of anti-HBs arc shown in Table m. Multivariate
comparison between the two recombinant vaccine groups shows that they do noc
differ in rates of increase of anti-HBs (F3, 1<M '"' l.99; P > 0.1). The 10-µg group had
significantly higher GMT of antibody overall than the 5-µg group (tu>6 2.08; P < =
0.05), although the difference appears to be small after the booster dose.
Multivariate comparisons of the anti-HBs profiles in the S-µg and 10-µg recom-
binant vaccine groups against the corresponding plasma-derived vaccine groups show
TABLE I. Frequency of Side Effects by Type ol

Vamnc (Summed Over Admlaisualions or Veccine)
Recombinalll Plasma-den vtcl

Side effect vaccine(~) vaccine I 1')
Local pain 6.0 9.0
Fever <37.5"C 16.3 II.I
Olhcr 2.3 2.3
Tow 24 .6 n.,
TABLE ll. Number (~ ) ol Scrotonvcrted (anti-KBs ;:, 1.J IU/1) by Moalh and Type of Vacdnt
Recombinant vaccine Plasma ,derived vaccine
S Pl 10 l'I 5 ,., 10 "'
Month (N • 55) (N • 55) (N • 50) (N • 50)
I
3
33 (60)
55 (100)
37 (67)
S4 (100)'
'°(80)
49 (91)
32 (64)
49 (98)
6 55 (100) S4 (100)' 49 (98) 49 (98)
7 5S (100) 53 (100)~ 49 (98) 50 (100)
"One penon lost 10 follow-up.
'Two persons lost.
Recombinant Hepatitb 8 VICCine 61
population, with all participants in both the trials of recombinant and plasma-<icrived
vaccines being males of similar age living under exactly similar conditions.
Comparison of lhe 5-µ.g and 10-µ.g doses of recombinant vaccine shows a small
advantage to the 10-µ.g dose overall in terms of GMT anti-HBs, although any final
difference is slight. Davidson and Krugman [ 1985), with older vaccinees of both
sexes, reported a final (8 months) GMT anti-HBs in the 10-µg group more than
double that in the 5-µg group, although the statistical significance is not stated.
Irrespective of dose, all participants in our trial reached the 10 IU/l generally regarded
as protective. Only five (4.6%; two from the 5-µ.g group and three from the 10-µ.g
group) had titres lower than 100 IU/l.
Our results confirm reports of the safety and immunogenicity of the Merck
Sharp and Dohme recombinanl yeasl hepatitis B vaccine (Jilg et al, 1984b; Davidson
and Krugman, 1985). The minor differences observed in the immune response stress
the need for more extensive studies in various population groups under consideration
for vaccination. before the appropriate dose and vaccination scheme arc decided.
Similarly. further follow-up is required to establish the duration of protective levels
of antibody [Jilg ct al, 1984a; Davidson and Krugman, 1985]. Finally, in assessing
the efficacy of the vaccine. infonnation concerning the quality of the anti·HBs induced
should complement the data on the anti·HBs levels achieved [Brown cc al, 1984].
ACKNOWLEDGMENTS
This study was supponcd by a grant from the Ministry of Hcalrh and Welfare
of Greece.
REFERENCES
Beasley RP. Lee GC. Roan C, Hwang L. Lan C. Huang F. Chen C (1983): Prevention of pcrilllWly
uuwniaed hcpatilii B Yina5 infections with bepatilii B immune globulin and hepatitis B Yac;cine.
Lancet ii:1099-1102. .
Brown SE. Ziackcrman AJ. Howard CR, Steward MW (1984): Affinity of antibody responses in man 10
hcpatilis B "~inc dcicrmincd wilil synthetic pcptida . Luicct ii : 184-187.
D1Yidson M. Kmgrnan S (1985): lmmuqeniciiy of re(Ombill&J\I yeast hepatitis 8 vaccine. Lancet
i:108-109.
Hollinger FB. Adam E. Heibc:r1 D. Melnick JL (1982): R e ~ 10 hepatitis B vaccine in a young adult
populalion. In Szrnuness W, Alter HJ, Maynard IE CedsJ: -viral Hepatitis. 1911 International
Sympo5i11m." Philadelphia: Fnnklin lnslia,t.e Prus, pp 45 H66.
Jil& W, Schmidt M. Deinhardt F, ZachoYal R ( 19841): Hepatitis B YKCination: How long does prot.eetion
last? Lanc:a ii:458.
Jilg w. Schmidt M. Zoulek o. Lorbccr B. Wilsu 8, Deinhardt F (1984b): Clinical CYaluation of a
recombi.iut hcpauci, B YICCine. Lanccl ii: 1174--1175. .
Maupas P, Chiron JP. Barin F, Couraa,et P, Goudeau A, Perrin J. Denis F. Diop Mar 1 (1981): Efficacy
of hcpaliu, B vaccine in prevellion of early HBsAg ca1Tier 11&1e in children. Co111rollcd trial in
an endemic: ara (Senegal). Lancet i:289-292.
McAleer WJ. Buynalc EB. MaigeUer RZ, Wampler DE, Miller WJ. Hilleman MR (1984): Human
hepatitis B Yaccine from recombinant yCISl. Narure 307:178-180.
Morrison DF ( 1976): ·MultiYariatc St.atislic:al Mcdlods, M (2nd ed). New York: McGraw-Hill.
Papaevangclou O. R~liOIOU-JCuayallllis A. Vissoulis C. Richardson SC. Kru1man S I 1985): IIMlll•
qcnicity o( 1 5 I'S dose hcpat.iti1 B vaccine. Joumnl of Medical Virology. 15:65-69.
Papaevan,elou G. Roumeliocou-lurayannis A. Vissoulis C. Sanhopoulou P. Kolailii N. Krugman S
( 1983): Sn(eiy 111d immuqeniciry of a further reduced d05C ( 10 mes) of \he hepatitis B vKCinc.
01040
L~L'NOGEHJCITY OF aEC.OAUIISA.."IIT \'EAST

HEPAT1'TIS B VACXl:SE
Slo.,-ln Dr Jil& 111d collal\lft' mady (Sew 24, p 1174) ill wny
rmpic11u of ..--bi1111111 btpmim 8 ncciDc "rllt 8IIIIIIIIIC
fflponte ill the recombilwu Wffl:Ulf lfoup -
dwina tbt r-
let.I ~
~ ,1111:1 ill ,be plan ''ICCUIC sn,up,
II,· lo-aw woconwnioa nres IIDd io-, - -;.Ha. 1ne1s•.
u.,..
TIiey compwccl a 10 l'I doec o r ~ nmac with a 20
cloot of plua-ckri"'4 ftCCiDL
& iadicatld ill die llblt, Ollf rawa ill a simibr 11\!dy ill -
buodml and -11 xra:wpti9' baJ&II pro(euioclala, 21-JO J'llll'B
or ag,. rnaled 1UCDtially die - imm1111e rnpouc ia ra:ipiaaa,
of 5 Ill and 10 ,c dDICI of remmbi111Dt yua liqlatitis I ncmc
w,hta romparccl with 1 -..,able pup w,11o received 20141 dam
ol plaaa:nHCri\'N WKQ&
Valid CDDdllliam - bic . . _ &- ll\ldia ill llliny • ·•

lwDdral ftlXlllftl. Mllff atni&iw fflMlittl will lir nqui,ecl ID
n-.lua1r an1i-HB1 mpgaac 111d i11 pcnill~ ir. napic:Du .r
ftCOlllbiND! liltpatitia II n«inc. ID &!It IIICllltimrt, llllf imti■I raul11
an aico11r1p11.
),"'l'\'......,C-,
.... , . _ ..,. . . , .. 1:111
TlfU.At.crT,JA!..'\'Aln' 12. 1915 109
llllCICOh'\'IAIIOl, Uftl AMI> ca,,unuc M1AX TITUI IGMTltll IDONIGATM INDMDU&U. ._,_n GrVD: UCDMIIIJW,."T 00
fUIMA.OU.l\'ID MIPAT1TIS I \ ' ~
■-r. -t
101'11
,,. ,__ ._(20,..,t
,_,
T-•
0
I ~
--.
Altt•HI•
.....,.,
.a-,,,.,..,
11n:1a1
CGMT)
..
G
s,,,.;,....
CGMT)
..19
,,
..,...
AA-Hit
..
21/M,,,..,
dt:181
(GMT)
..
"
11!,1-
C(iMT)
..
21
.......
Aac>Hlle
..
,.lll41IJ",I
. .,c,,.,
l'-111•
IGMT1
..
JI)
2
J
,,.• '°"''""'
49'10111"1-J
0'46CIAI
m
II
Sll
ltll
.,
S2
1'4
tl/Sf.11,.1
SJMCJll,I
SMt(IMol .
4MO~I
IO
,,. .
UII
114
~
.,''
l>4
..,..,,,..,
•Sl47 Clftl
..... ,..,.., .
17
fl
141
Div1dson ~. Krugln!iln S. I nogen1c1ty of recotm1nGnt yeist h.!_l)Qt1t1s B v1cc1ne.

L@ncet 1,es; 1:108-9.
010~1
RECOMBINANT YEAST H'EPATITlS D VACCINE: SIDE EFFECTS AMO

IMMOWOGENICITY COMPARED WITH PLASMA-DERIVED HEPATITlS B V~CCIHE.
Morton Davidson and Saul ~rugman
NYU Medic l Center, New York, N.Y.
A yeast recombinant hepatitis B vaccine (Merck Lot no. 972/C-
K444) was eval u ted in 197 seronegative health professionals, 21-
39 years of age. The clinical and antibody responses were
compared with the results of a previous similar study using a
plasma-derived hepatitis B vaccine (Herek Lot no. 7S1).
~he vaccine was admirtistered ate, land$ months to the
following three groups: l) 51 adults who received a 10 mcg dose
of recombinant vaccine;-2) 56 adults who received a S mcg dose of
recombinant vaccine, and 3) 47 dults who received a 29 mcg dose
of plasma-derived vaccine. The three groups included medical
st udents, house staff, and nurses who were of compar~ble age and
sex.
Results
Side effects were negligible in all three groups. They
inoculation in about 2S\ of the vaceinees in each group. No
systemic reactions were observed.
The seroconversion xates and geometric mean titers are
summarized in the Table. The results are essentia lly the same for
all three groups. Under -the conditions of this study the 5 meg
and 19 mcg doses of recombinant hepatitis B vaccine were, just as
immunogenic as a 2S mcg dose of plasma-derived be~atitis B
vaccine.
Comment
A recent report by Jilg et al (Lancet 1984; 2:1174-75)
described a similar study in 39 seronegative medical students and
laboratory-workers whose age and sex were comparable to those in
our groups. They stated that "the immune response in the
recombinant vaccine group was less pronounced during the first
months than in the plasm, vaccine group, as shown by lower
seroconversion rates . and lower mean anti-HBs levels." Our results
in 197 similar . recipients of the recombinant hepatitis B vaccine
do not support this conclusion • .
It is obvious that valid conclusions canno~ be drawn from
studies involving either 39 or 199 vaccinees. Meie extensive
studies will be required to determine anti-HBs response and its
persistence in recipients of recombinant hepatitis B vaccines.
D v1dson , Krugiun s. R c 1nent ye&st hcpat1t1s B v~cc1n: Side effects

1nd 11111a1noeen1c1ty c M w1th ples -deriv d h pmt1t1s B vaccine.
sutmitttd for pub11c1tion to Hep&t1t1t Sc1ent1f1c !il!Prfnda.
01042
TABLE
Seroconversion Rates and Geometric Mean Titers of seronegative

Adults Who Received Recombinant Yeast Hepatitis B vaccine (Merck
Lot No. 972/C-K4•4) or Plasma-Derived Hepatitis B Vaccine (Merck
LO t ~No • 7 5 l) •
T1me Recombinant Hecatitis B Vaccine

Interval 10 mccr dose S mcq dose
anti-HBS mlU/ml S/N Ratio anti-HBs mIU/ml S/N Ratio
(Months) reseonse GHT GMT reseonse GMT GMT
0
1
-
22/51 (43%)
-42 -
19
-
:1/S6 (37%)
-
ss
-
25
2 48/51 (91.%) 88 37 51 /56 (9,l.%) 69 38
3 50/51 (98%) 145 52 52 /56 (93%) 128 Sl
6 49/50 (98%) 321 63 53/S6 (95%) 184 42
8 1,5/46 (98t) ,Cl}] l ~l. 1.9/50 (98%) 839 1 ?lo
Vaccine given at 9, land 6 months.

Time Plasma-Derived Hepatitis B Vaccine

Interval 20 mcq dose
anti-HBs S/N Rll tio
(Honths2 resconse GMT
0
1
-
18/47 (38%)
-20
2 34/47 (79%) 37
3 45/47" (96%) 79
6 44/47 (94%) 94
7 46/47 (98%) 141
Vaccine given at 0, land 6 months.

A9e range: 21 - 30 years
01043
SAT-LA-10
CUHICAL EVAL0ATION OF A RECOMBINANT HEPA'l'tns 8 VACCINE
F. Deinhardt•, W, Jilf, 0. Zoulek, B. 1.crbeer, and B. Wllske
Mu von Pettenkofer-Institute, 8000 Munchen 2, Western Oermuy
Thirty healthy, younr volunteers free or any HBV mukers were vaccinated with ~ recombinant
hepatitis B vaccine prepued by Merck, Sharp & Dohme, West Point, PA. Ten I.ti HBsAg were
administered lntra ,nuscularly a t time 0, a nd one month la ter. Seroconversion rates and ceonietric meaa
concentrations a fter 1, 2 and 3 months were compued with an are- &.nd sex-matched control rroup
vaccinated with 20 JC of plasma derived vaccine (Merck Sharp & Dohme) (Table 1).
Ta ble 1: Comparison or Immune response after recombinant vaccine and pluma derived
vaccine.
month 1 . .oconversion anti-HBs (geom. nsean)
96 mlU
recombinant plasma recombinant plasma
vaccine vaccine vaccine vaccine
1 21 44 1.6 15.2
2 70 t5 37.1 52.5
3 91 95 27,4 164.4
In the recombinant vaccine group, 31CJ6 of the total uU-HBs et month 3 was directed against the
determinant a of HBsAC, compued to 30'i\!i ln the control rroup. No increase In antibody titers against
candid& albicir\, was found In recipients of the recombinant vaccine 4 weeks after the second Injection
as compared to Pfevacclnatton levels. No Htious side eCtects Ytere ob5erved ln any of the vaccinated
individuals: ·
Deinhardt f. J11~ , Zoulek 6, Lorbeer 8, W11skt 8. C11n1tal eva luation of a

recombinant hepit1tis • B vaccine. In: Vyu SN, D1enstag JL, Hoofnagle
JH, eds . V1r&1 Hep t1t1s 1.ind LivEr Disease . 0rl11ndo:Grune &nd Straton,
1CJ84:699.
01044
llECOMBJNA,.\"T YUST lt!:PATITlS i VACCINt: L~OC:DflC!TY AJ.'1>

$AFtT'!. A 1>hnstag 1 t 'llu'dne 1 and CA IUn'lth, .
Caa trolnt es t1na l Unit, Masaachuocttl Ccnc r a l Ho1piul,
loatoo, ~J.. .
c - lM!r•-• to pro4vc c, czpcn11va, a!MII 11-ited in
aupply, cvrr cntly • • • 1labl c hua.a pla1a1-der1ved ha~atitie
I va ccines a r c li~e ly to be repla ced in the Cutvr• by
•a•n• tica lly cnginec r ec" vacciJlea. lece~tl7, •
r ec-bt.nant DKA vaccine vaa prepared ta r cc-bt..e.ult yeact
S a ccharOWtvc c ■ ccr • •1•1ac ■ train 21~2-l cells tT&nc for-ac d
Vith the pla ■ald pHIS )6-Cl.7347/33, coata 1A1a& the 1n e
for hc pat$t1a l . ■ ur! a c c antiaca (Hl cAa/~l (Va Leuvela et
al. ~a tvr e l912; 29a:l47-~0). Pvri!iad lo)' \iochesical -~
biophy1ical M tbod ■ fr oa the 7ea1t aztract, the Dug
particle, 1ynthe1 i1cd by these 7ca1t ce ll• ar c aot
slyco17laced but othccvi1c arc incli ■ tiarui •ha •l • fr-
a a t1•e 2l - XleAg particlea. Treated vith fo raalia UICI
adaotbcd to alua, the r ccoabinant vaccine 11 u:a111101en1c
and proc c ct1vc 111 cxper1"nta l aaS.-11. _ 'lie aca in1etc r ed
three 10 u& do1c1 of the rec-binanc hc , e ttti.s J.vacc1Ac
(Merck Sharp l Dohac lcscarch 1.al>oracor1cs) a c t1- 0, 1 0
and 6 aoatha to 60 1crone1a t1vc adult hcalch workers. The
fr~qu cacy and acoec crtc acaa titer (s tUls l) of anti-U c
T••-n••· vcrc •• (ollov1 :
tlonch l 2 3 4 5 6
>luaber 37 2, lO 2, •2~ 1'
anU-Hl a• 41% • Ut ,Jt '71 !6% ,,1
arr 1 S1> 7: 2 33: ~ 36:, ,, : , 55:, ,, : ,
,, : S i -• n :.Sil) 1 of the anti- Hl1 va1 1pccil1c for the •
.!. dc t cmin&11t of HlaAg. Chaos•• 1D arac1M4!ic• co 7•••t
aaci s•a • verc oc111&1blc. The aost frequent advcr••
r e1cti011 va1 tf&Al i e nt 1orcnc1a at the ~J • ctioa 1ite,
occurrins a ft e r 521 of !ir1c, 37% of secoad, aod 55% of
third inJ ccc1on1. )lo 1cr1ov1 1dv1r1c 1ffccc 1 v,rc
cncouatcred, and aetthcr t)'?C I nor ua• I hcpa t1t11 has
occurr ed ta aay v ■ cc1ncc. The•• pre liaiury r c ■ l&lt a
dc:aon1tr a cc tha t the r ccoebiaant 1•a•t he pa titis I •accinc
1• 1afc and that 10 us of the r , c- hia.Jt.t v acciac 1•
cqu1valccc 1D u=uaoscoicity to 20 VI of the
pl asaa-sd crivad vaccillc.
D1ensteg JL, stk1ns E, Hinkle CA. Rec0iib1nant yeast he~~t1t1s B vaccine:

1rounogen1c1ty ind safety. Hep1tolopy lt84; 4: 1077 (AbstrBct).
010Q5
'SA't!-.LA..50
SAFETY AND lMMUNOOENlCITY OF A RECOMB[NANT HEPATtns B VACQNE
J.L. Dle,-stq•, E. Watkins, and C.A. Hlnlc.ltl
Outrolntestlnal Unit (Medical Senices), Musachusetu Oeneral Hospital, gnd Department or
Medicine, Huvard Medical School, _Boston, Massachusetts DUH
Currently 11vailable, licensed hepatitis B vaccines are prepared Crom plasma obtained from hepatitis a
surface antigen (HBIA() carriers. Cumbersome to produce, expensive, and available In limited sups,ly,
the plasma vaccine is likely to be replaced in the future by one oC a number or later generation vaccines.
Recently, 11 recombinant D~A vaccine wu prepared In recombinant yeast Saccharomyces cerevisiae
strain 2150-2-3 cells transrormed with plasmid pHBSS6--0AP34T/33, which contains the rene for HBsAt
(Valennela et al, Nature 1982; 291:347•501. The H&Ag synthesized by these yeast cells was puriCie<I
Crom the yeast extract by physical and chemical methods and was round to be lndistinruishable from
native 2i nm HBsAg particles, except that the HBaAg b not rlycosylated. Treated with formalin and
adsorbed to alum, the recombinant vaccine b comparable In purity to the plasma vaccine and ls
Im munorenic and protective In exp4trimental animals.
We studied the lmmunoreniclty and safety or recombinant hepatitis B vaccine Lot 934, Cormulated to
contain 10 microrrams or KBsAr per 1.0 ml dose (~erck Sharp 6: Dohme Research Laboratories). Thirty
seronerative adult health care workers received three 1.0 ml doses or the recombinant nc:cine at tirne o,
1 and 6 months. Adverse e!fects were Umited to soreness at the injection site, and immunogenicity was
excellent, tppf'(!XimaUng 50'16 at one month. Three months or Collow-up will b<c complete by the time or
the International Meeting.
D1enstag JL, watk1ns E, Hinkle CA. Safety .mnd 111iftunogen1c1ty of a recombinant

hepatitis B vaccine (Abstr&ct). In: \fyu 6tl, D1enstag JL, Hoofnagle JH.
eds'. V1ra1 Hepat1t1s and Liver Disease. Orlin~o:6r~ne ind Stratton,
1984:710. ·
tH 046
Anrfrira/ Rurarcn. Suppl. I (l98S) 273-279

Pro,. In Int. TNO Con!. Antiviral Res. l9S5 Rotterdam
A. Billi~u. E. De Clercq and H. Schdlclccns (eds.)
c 1915 Elsevier Science Publishers B.V. (Biomedical Di,·ision)
1munt RESPONSE AFTER VACCINATIO:i WITH P.ECOMSINANT HEPATITIS B V.O.CCIN[ AS

CO:~P.D.Jl[O TO THAT A:'T[R PLAS.'iA-OERIVEO VACClNE
R.A.liElJT!t:1:., J.tRUllUNG, H.SAKK.ER, S.W.SC'nAUlt

De~tr~nts of Virology and Internal ~edicine, Erasmus University Rotterdam,
Rotttrda~, The Netherlands
su~~:.IiV
Thirti-one indivicuals (he~lth care workers) were vaccinated with recombi-
n!nt he~!titis B vaccir.e (10 µg dose) and their imune response (anti-MBs)
was c~~pered to th~t of twenty-five health care worklrs after vaccination
with plasraa-deri~d viccine · (20 ~9 dose). Al"though the _seroconversion rite
and the percentage of anti-HB\/a antibodies at 1110nth 7 were comparable, the
geometric mean titre of anti-Hils at 110nth 7 was considerably lower for the
recombinant . vaccine group (857.4 vs. 6736.S lU/1_). However, vaccine~s fraa
the two groups shewing seroconversion at 1110nth l had COIIIP&rAble titres at ·
11101\th 7. Raising the dose of HBsAg in the_ recombinant vaccine inay favourably
influence the seroconversion rate at 1110nth 1 and thereby the imnune response
after three injec~ions.
IHTRODUCTI~l
Only six years ago, a ·plasm-derived vaccine was introduced to oven:mnt
the worldwide problem of hepatitis B infections. 1 General acceptance of the
vaccine, ho-..ievtr, has been hampered by the high costs and in particular by
dou~ts about the suitability of infectious plasma as its source. Public
concern has waned considl!nbly since the discov_ery of h\Aln T-cell leultaeaiia
virvs as a possible cause of the acquired innune deficiency syndrome and the
possibility of investigating the efficacy of inactivation of this virvs in
vaccine preparation procedures. 2 Meanwhile, an alternative for the latter
objective has been found in the preparation of hepatitis B surface antigen
by recombinant llHA technology· in the yeast _Sae~c•• c•ravuica. 1
Although the yeast recombinant ONA ~roduced HBsAg polypeptides, unlike the
nat~ve HBsAg, are not glycosylated, the vaccine thus prepared has prove_n to
induce protective antibodies during chi111panzee ~hallengE, studies.' Its
safety and i111municity in 11an has bee~ demonstrated by se-n:ral groups of
investigators.' 1 7 1 ,One of these studies is c,resented here.
273
01047
Soon after the introduction of the plasllll-Gtrived vaccine it was uncertain

whether an HBsAg/adw vaccine would protect tgainst HBsAg/ayw virus infections.
r.o..adays it is generally known fron chir.-.panzu studies ,swell as exper-ir.aents
in man 1 ' 1 ~ th•t the antibodies direc:ed a94inst the 111ain determinant!
pn,vide cross protectfon for infections wi _th strains not incorporated in the
vaccine.
However; in the plasma-derived vaccine studi u 11 12 it was found that th~ rela-
tive proportion of ant i-HBs antibodies is variable, which 1114)' partially 1ccount
for hepatitis B infections in the first few 1110nths after vaccination. There-
fore, the ne!d to ~.onitor the developr.ient _of anti-HSs/a antibodies after
vaccination is stressed.
MATERIAL AND METHODS

Popuhticin .
The study population consisted of 56 health care workers. Recombinant
viccine was given to 31 individuals (17 fem~le. 14 mle; 111ean age 32 ~
2 yr, range 20-59); plasma-derived vaccine ~as given to 25 individuals
(13 ·fe~ale. 12 male; mean _age 30 !. Z yr. range 22-53). Participants to this
study were negative for. HBsAg, anti-HSc, and anti-HSs and had a normal
alanine transferase level at the entrance to the study.
Vaccine
Partic1pints were vacc~nated at O, l, and 6 1110nths with either a 10 µg
KBsAg/adw dose of the recombinant hepatitis B vaccine {Kerck, Sbarp and
Dohme, lot 972/C-i444) or a 20 ug HBsAg/adw dose of the plasma-derived
_vaccine (Merck, Sharp and Dohme, lot 1510 J). Recombinant HBsAg used here
1 1
was purified.
by hydrophobic interaction
.
chronatography.
.
Assays
H8sA9. 1nti-HBc, anti-KBs were 11easured in c011111erci1lly available kits
(Ausria II. Corab, and Ausab; Abbott Laboratories, . North Chicago, USA).
The concentration of anti-HBs was calculated by tbe Nthod of Hollinger
et al. 11 and _expressed· in IU/1 after COllll)&rison with the IMO standard pre-
paration (125 IU/1), obtained from _the Central laboratory of the Netherlands
Red Cross 81ood Transfusion Service, ~sterdut, The Netherlands. Calculations
were 111de for positive results in Ausab only (sample/negative control ratio
-~ 2.1). Sanples containing 110re than 200 IU/1 were diluted and retested.
Dilutions were ~ade in the negative control ser11111 from Ausab. Estimation of
the proportion of anti-KSs/a antibodies was perfonied according to the
111ethod of Hoofnag1e et al.'' In short, undiluted or diluted sera conta~ning
1000-2000 cpcn in Ausab were incubated for 2 hat room teaaperature with
pooled HBsAg/ad, H8sAg/1y, ind noniial hunan serun, respectively. Pooled ser1
274
010~8
included reference sera from Or.A.M.Courouc~·?auty as mentioned in an earlier

study.I'_ Reduction of cpm after incubation with HBsAg/ay stnins meuured
the anti-HBs/a proportion of the total amount of tnti-HBs. since the vaccine
consisted of KB~A;/acw only . The· proportion of ~nti-H8s/d(w) antibodies was
obtained by _subtr,cting the reduction percentege after incubation with
HBsAg/ay pooled ser-un from the reduction percentage after incubation with
KSsA;/ad pooled serUIII.
ll£SULTS
Table I sh01ots • delayed seroconversion rate for the recombinant vaccine
group as compared to the plasma-derived vaccine group in the course of the
vaccine study . Sinilar results were obtained for titres~ 10 lU/l. the
supposed protective level of antibodies.
TABLE I
SEROCONVEP.SIOtl .RATE AFTER VACCINATION WITK RECOOINAlff (10 1.19) ANO PLASHA-
OERIVED (20 1.19) VACCiNE IN ~EALTK CARE WORKERS
Month Reeombina.nt Plasma-derived Reconrbinant PlaS111a-derhed

vaccine vaccine vaccine vaccine
Percentage seroconversion Percentage anti-HBs
~ 10 JU/1
1 19( 6/31) 56(U/25) 13( 4/31) 40(10/25)

2 77(2'1/31) 96{ZZ/23) 39(12/31) 74( 17/23)
J 90(28/31) 100(25/25) 74(23/31) 96(24/25)
Ii 94(29/31) 100(25/25) 87(27/Jli 100(25/25)
7 100(31/31) 100(22/22) 100(31/31) 100(22/22)
Ge0111etric inean tHres of anti-HBs were significantly lower in the recombi-

nant vaccine group as C011pared to the plasm.,-derived vaccine group at 110nth
z. 30 6 0 and 7 (Table II).
After three injections females had significantly (p < 0.05) higher anti-
HBs titres than ■ales in the r-ecoabin&nt vaccine gT'Oup (1412 vs. 468 JU/1)
but not In the plasma-derived vaccine group (6036 vs. 7519 IU/1).
All vacc1nees were negative for HBsAg and anti-HBc at 7 1110nths and had
nol"lllil alanine transferase levels in all sera obtained. Table Ill illustrates
the increase of the relative p_roportion of anti-HBs/a antibodies frU11 about
Ii~ at month l to about 10~ at 110nth 7 following the first injection for
both vaccine groups as me&sured by specific absorption. In any sample at
275
TASLE II
GEOi~ETR!C ~l[AN TITRES OF ASTl•!-!Bs AFiER \'ACCliiATlO:; WITH RECOMBINANT VACCINE
(10 ;:g) A!IO PLAS~IA-OERlVED \'Ai:CINE (20 119)
Hon th Re~omb~nant vaccine Plasma-derived vaccine

GMT in IU/1 GMT in IU/1
l 16.B(ns 6l 1g.7(n"14)
z 13. 7(11=24) 61.B(ns22) 0
3 34.B(ns:28) 177. 7(n•25) 0
6 69.0(11•29) 2!!l . l(n•2.S)O
7 857 .4 (n•Jl) E736.5(n,.22) 0
O
t Responders o~ly p< 0.05 Uilcoxon's ~ank sur1 test
.TABLE Ill
OETEP.MINATION OF SUBDETER:~INA.'U SPECIFIC AHTIBOOIES AFTER VACWIATION WITH
RECO:-tBIN~T VACCINE (10 119) A.~D PLASMA-DERIVED VACCINE (20 119) PS OETEi!MINED
BY SPECIFiC ABSORPTION
Month Recombinant vaccine Plasma-derived vaccine

No. : anti- Santi- No. Santi- : anti-
samples HBs/a HBs/d sanp les Has/a HBs/d
(r1nge) (range)
l 4 . 60( 19· 92) 1 39 6 57(22- 99) 42

2 9 81(4!>- 98) 17 15 83(25- 99) 17
3 18 95(74-100) 5 23 88(26-100) 11
6 26 99(89-100) 1 24 94(43-100) 6
7 31 99(90-100) 1 '22 97(91-100) 3
R Oetenaination of ariti-HBs/a and anti-HBs/d was liaited by the mini,;__

1110unt of 25 IU/1 anti-KBs.
nonth 7 the proportion of anti-~Bs/a antfbodies ins at le1st 90:. Jn sera

with anti•KBs ~ 10 lU/1 at 110nth 1, two out cif four in the recori>inant
vaccine group and three out of si~ in the plaS1111-derived vaccine group hid
less than so:; anti-HBs/a. ln only two cases. one in each group, the anti-
HBs/a percentage at 1110nth 1 was •bove 90, suggesting an anemnestic response.
Geoinetric •inean titres for thOse vaccinees with a positive anti-HBs response .
"276
01050
at month 1 increased to 11158 IU/1 (n=S) in sera from the recoabinant vaccine
group and to 13748 IU/1 (ntl3) in sera from the pl•siu-derived vaccine group,
both at 110nth 7.
DISCUSSION
Table IV co11pares the result~ of the im1unicity of recombinant hepatitis B
vaccine of Herek, Sharp and Oohr.~ in our study with results of others as
recently pu~lfshed. ' • 7 • Severe! lots of vaccine with ainor differences
in the purification procedure were used. Comparison is made in s0111e studies
\oith earlier results using phs.w-derived vaccine from the sa111e 111nuhcturer,
ln our· study veccinHion with rtc(l(llbinant vaccine and pluina-derived vaccine
took place sim~lteneously. Serv111 samples could therefore be handled similar-
ly and investigated with the same batch of reagents.
~e found 1nti-HSs develop111ent during•the first six 110nths following the
first injection very similar to Scolnick et al. 5 ind Jil~ et 11.'. After
the booster ir.jection at 110nth 6 we found a lower ge0tnetric 111ean titre than
o~served by others . The proportion of anti-K8s/a antibodies, however, was
very similar for the two v1ccine groups and incn!ased fM)ffl 61r. at 110nth l
to about 100! at month 7.
Interestingly, we noted high titres of 1nti-H8s at 1110nth 7 for tnose
v,ccinees who had already shown seroconversion at 110nth 1, Titres in thfs
subgroup were c0111p&rable to those in early responders in the plasma-derived
v1ccine group . Since we had the lowest seroconversion rate at 110nth 1
observed so fir for recombinant vaccine (l~). this inay explain the low
geometric 11ean titre 1t 1110nth 7. The re1son for the initial low conversion
rate in our study is unknown. Sex and age ·d ifferences with other study
groups 111ay have contributed. Sex and age effects •ay have their 110st pro-
nounced influence on vaccination of weak responders. 11 17 The highest sero-
convenion rate (67:) and the highest geometric 11t1n titre (2749 IU/1) at
mnth 7 were observed by Papaevangelou et al. 1 in .male recruits aged 17-19
yun.
If our observations can be confinned in 110re extended studies, equalizing
the dose of HBsAg in the recombinant vaccine preparation to that of the
plaSN-derived v1ccine iuy favour1bly influence the seroconversion rite at
110nth 1 and the 1110unt of anti-HBs . produced 1fter three injections.
ACKXOWLEDGEHEHT
We thank Hrs . R.S.Engels-Bakker for preparation of the aanuscript.
277
TABLE IV
J~IHUNE .RESPOIISE: AFTER VACCINATION WITH RECOMBINANT AND PlASHA-DERlVED HEPATITIS D·vACCllfE I\S COMPARED rROH LITERATURE
Author, Dose Geocnetrl~ mean ·titres in tU/1 No. Hean l!JC · lfo. of No. of Lot no.
llll!n women
Honth
·J 6 7
Recombin ant v1tcfne
Scolnlck et al. 1 10 µg 8 -56 68 1905 15 ll,ZJ-53 10 5 934

Jllg et al. 1 10 µg 9 29 68 2135 30 !S,21-34 I) 17 934
~ 198 189 2749 55 17-19 55 979
CD Papaevangelou et al. • 10 11!1 11
Davidson ahd Krugnian' 10 11!1 42 145 321 1911 51 21-JO 972
Present study JO 11!1 17 JS 69 . 0S7 31 32,~0-59 14 17 972 .
Pla1m1-dertv1d vacctne
Jilg et al. • 20 11!1 15 164 263 4299 41 ZS,21-32 18 23

Present study 20 \19 20 177 291 6737 ZS 30,22-53 1Z 13
Papaevangelou et 11.• 10 µg 4 278 492 9227 so
-
0
-
I.II
01052
R£FHENCES
1. sz~uness W, Stevens c~. Zang EA, Harley EJ, Kellner A (1981) Hepatology
1: 377-385
2. Stevens CE, T~ylor PE, Rubinstein P, Ting RCY, Bodner AJ. Samsadharan
l'IG, Ga1lo RC (1985) N Engl J Med 312: 375-376
3. Valenzuel1 P, Medina A, Rutter WJ, /.mlllerer G, Hall BO (1982) K•ture
298: 347-350
4. HcAleer IIJ, 8uynak ES, Htigetter RZ; Wampler OE, Hiller WJ, Hilleman HR
(1984) Nature 307: 178-180. ·
S. Scolnick EM, Hclean AA, \lest OJ, t'.cAleer WJ, Hiller WJ, 8uyn1k. EB (1984)
J Am Med Au 251: 2812-2815 .
6. Ji\9 W, Lort>ur 8, Schmidt K, \lilske 8, Zoulek G, Deinhardt F (1984)
Lancet II: 1174-1175
7. Devidson H, Krugman S {1985) uncet I: 108-109
8. Papaevan9elou G, Dandolos E, Roun,eliot~u-Karayannis A, Richardson SC
(1~85) Lancet I: 455-456.
9. Barker LF, Maynard JE, Purcell RH, Koofnagle JH, Berquist KR. london WT
{1975) k:t J Med Sci 270: 1S9-195
10. Szm~ness W, Stevens CE, Harley EJ, Zing EA, Alter KJ, Taylor PE.
De Vern A. Chen GTS, Kellner. The Dialysis V1ccine Trill Study Group
{1982) N Engl J Med 307: 1481-14116
11. Legler K, Strohmeyer H, Ritter S, Gerlich WH, Tholllssen R {1983} Develop
Biol Standard S4: 179-189 .
lZ. Jilg W, Delhoune C, Deinh•rdt r, Roumeliatou-~rayannis AJ, Papaevangelou
CJ, Hushehwar Jl, Overby ~R (1984) J 1'4ed Viro·l 13: J71-178
13. Hollinger fll, Adam E, Heiberg D, Melnick Jl (1982) ln: Stainus V,
Alter HJ, Haynard JE (eds) Viral Hepatitis. Philadelphi•, Franklin
Institute Pres5, pp. 451-466
14. Hoofnagle JH, Gerety RJ, Scullwood LA, Barker LF (1977) Gastroenterology
72: 290-296
15. Hetjtink RA, Van fflttum J, Schalm SW, Hasurel Ii (1982) J Med Yirol l_O:
83- 90
16. Heijtink RA, De Jong P, Schal~ SW, ~.a5urel N (1984) Hepatology 4: 611-
614
17. Suvens C[, St111Uness W, Goochin AI, Weseley SA, Fotino H (1980) L1ncet
It: 1211-1213
279
01053
ANTI-HBs/~ DETERMINATION An'ER HEPATITIS B VACCINATION
Sir, - Th1: deurminatirJn of Aintibudiu :ll!:tinHt ll1•: ~ tf•:lt•r1ni,,:u1l (r,1111

HBsA1 ~ft r v ccination vith H!sAg/adw is of interest. ~ince enti-HBs/a
antibodies re thought to be protective. Twc methods for aeagurement of
these Antibodies are io use: I) Specific bscrption of serum anti-HBs
1
vith pooled HBsAg/~y. The reduction of &nti-HBs, as measured in direct
tests for anti-H!ls, reflects the proportion of anti-HBs/a antibodies.
2) A radi~i:cunoassay or £LISA usi~g R!sAg/ay .as solid phase ar.tigen.
We applied methods I .and 2 on sen from our comparative study on the
imniunogcnicity of recombinant_ nd plu111.-derived vaccine, Thirt)·-one
health care workers wer~ vaccinated with recombinant vaccine and
tvcnty-five vith plasma derived-vaccine, both from Merck, Sharp 6
Dohme. All participants showed seroconversion at month 7. ln all
individual sera &ampled at month 7 ve found that the anti-HBs contained
9Cr-100% anti-H!s/a antibodies by method I in both groups of vaccinees,
as published elsewhere. 2 The percentage of anti-HSs/a according to
method 2 vas calculated from the geometric mea~ anti-HBs concentratio~s
found in Ausab (Abbott Laboratories) using HBsAg/ad~.&)"W coated beads
(Auubt) and in Ausab using HBsAg/ayv c·oa:ed_ buds (Auu.bay>· All nra
yere prediluted until the concentration in Ausabt was less than 200 IU/1.
For both assays, Ausabt and Ausabay' anti-HBs ~•• determined by linear
intrapolation of the results fr0111 the test sam~les in between the
results fro• a twofold dilution series of the WHO reference serum.
Results in the recombinant vaccine and the plasma-derived vaccine g~oups
shoved 80 and ,0% anti-HBs/a, respectively. An ELISA (Ortanon Diatnostics
Rese:srch Labs, Oss, The Netherlands) usint microtitre plates coated vith
HBsA&l&)'W, shov d 60 and 45% anti-llBs/a in the recombinant vaccine and
plasma-derived vaccine groups, respectively.
The specific absoTption method confirmed the findings o! Scolnick
et a1 3 (90-100% anti-HBs/a after recombinant vaccine a dministration),
Yhere.111 our re,;ults vith 111ethod 2 C nti-HBs/a "specific" tests) are
4
in . ~ccordance Yith those of Jila et al. (49% nti-HB1/ ·_ftef pl asma-
derived vaccine dmini1tr~tion). Our results show, however, that the
pp rent difference, in percentage &nti-HBa/a I published by Scolnick
He1jt1nk ftA. Schilm Stj, Ant1-H8s/i d tel"filin;t1on after hep1t1tis B vaccination.

Submitted for publication to Lancet.
OtOSQ
et 1. and Jilg ~t 1. mre u~t primarily releted to the differences in

the v ccinH but to the 111et_hodol0gy applied to Hseu nti-Hh/a £nti-
bodiu.
Which test iyatem provides the most useful deta? In D£thod 1. ~nti-HBs
antibodies re bsorbed vith n excess of pooled HB1Ag/ey 0 which may
contain other epitopei in addition to a- and y-related epitcpes. Hi&h,
but also low affinity ~otibodiea 5 re removed nd the reduction of
anti-HSs will be optim l. This test will likely overestimate the
percentage of neutralizing ~nti-HBs/a antibodies.
Problems vith the determination cf mnti-HBs/a by method 2 are
illustrQted in the figure. Anti-HBs/c containing rc~uents (unti-a
monoclond antibody, posi tivc control serum Au1111b test, tlit- i.'lll) rt>f.:-
t
rence standard containin& -200 IU/1) and anti-d nion<'clonal antibody \:ere
tested in various dilutions simultaneously in Ausab and Ausab
•
t ay
Monoclon 1 anti-a gave almost identical results in both tests, and
fitted the line of identity. About 10? (based on cpm) anti-d 1110noclcn£l
antibody measured in Ausabt was detected in Ausab ay , presumably as a
result of non-specific absorption. The line obtained with the Ausab
positive control serum vas also linear, but not'parallel to the line
o! identity. Results for the WHO reference serum sho~ed a cut·ved line.
Quantitation of anti-H!s/a usin& the Aus&b positive contr.ol and/or the
\.IHO reference serum as a standard is therefore in fact i~pcssible.
although both standards contain more than 90% anti-H!s/a antibodies.
accordin& to specific absorption. In our opinion. antibodies with
variable affinity and/or reacting ~ith different epitopcs must be
present to explain the discrepancies,
Detailed description of the anti-HBs response nfter vaccination is
important. The initial interest concerned the quantitative aspects,
Manyinvestigators are shifting their interest to the qualitative
aspect of the anti-HBs evoked by vaccines.
In our opiniofl, there is an urient need for unambiguous t st systems
for vaccine evaluation, especially vhen results from vaccines with
HBsAg from different eources (pl~sma, recombinant, synthetic) or with
different compo5itions (with advithout pre-s-polypeptides) are to
be comp red.
Departments of Virology nd R.A.HEIJTI~
Internal Medicine~ Er nius University, S.W.SCRALM
P.0.Box 1738, 3000 DR Rotterdu,
The Netherbnds
01055
J. Hoofnagle JH, Cerety u.Sm&llwood l..A 0 Barker LF. Subtyping of

hepatitis B eurfa ce &mtigen a n~ ~ntibody by radioimmuno ssay.
Castroenterology 1977; 72: 290-296.
2. Heijtink RA, Kruiuini J. Bakker M, Schalm S\l. Immune response after
vaccinat ion with recombinant hepatitis B vaccine s compared to
that aft er pla~-derived vaccine. Antiv Res (in press).
3. Scolnick EH, Kcl.e n M, ~est DJ, McAleer WJ, Miller ~J, Buynak EB.
Clinical evaluation in healthy dult s 0! • hepatitis B vaccine
111ade by recombinant DNA. J Am Med Ass 1984; 251: 2812-2815.
4. Jilg W, Delhoune C, Deinhardt F, loumeliotou-Karayannis AJ,
Papaevangelou CJ, Mushahvar IK, Overby Lk. Hep3titis B surface
antigen (HBsAg) s ubtype-specific antibodies in persons vaccinated
against hepatiti s B. J Med Virol 1984; 13: 171-178.
5. Brown SE, Howard CR, Zuckerman AJ, Steward MW. Affinity of antibody
responses in man to hepatitis B vaccine deten:iined with S)-nthetic
peptides. Lancet 1984; 11: 184-187.
Figure: Comparison between counts per minute (n&tut31 logarithni) in

•
Ausab t (HBsAg/ dw,
_
ayw coated beads) a nd Ausab ay (HBsA,/a~v
coa ted beads) in dilution series of monoclonal anti-a (e--41 ),
monoclonal a nti-d (~ e ), the WHO standard reference serum
(0---0), and the Aus bt positive control serum(~). The
dashed line repre~ents identical results in Ausabc and
Ausabay•
01056
10 ,,
>-
Ill
IJ 9
•::,
<--
.5
II
.!:,
C
.,.
i
7
C.
-tll
C
::,
0
-
1,1
.E
6
5
•
6 7 8 10
ln(counts per minute) in Ausab 1
01057
Maurice R. Hilleman, Eugene 8. Buynak. Henry Z . Markus.

Robert Z. Maigetter, William J. McAleer. Arlene A . Mclean.
William J. Miller. D. Eugene Wampler and Robert E. Weibel
·22
Control of Hepatitis B Virus Infection: Vaccines
Produced from Alexander Cell Line and from
Recombinant Yeast Ct:!11 Cultures
Human hepatitis B virus has yet. to be successfully grown in cell culture. Current
vaccines ( J-S) against hepatitis B virus employ hepatitis B surface antigen (HBsAg)
that is obtained from the plasmas of human carriers of hepatitis B virus infection.
The HBsAg stimulates antibody against the virus and prevents infection and illness
caused by the aeent. Available supply of suitable carrier plasma a nd the need to
apply highly te chnical procedures to purify HBsAg and to render it safe limit the
amount of plasma-derived vaccine that can be made and impose cost restrictions
on its use . We have sought to explore alternative sources of HBsAg to prepare
hepatitis B vaccine and have prepared and tested vaccines made from HBsAg
secreted from carrier hcpaloccllular carcinoma {HCC) cells (6) and from yeast
cells carrying an expression vector of HBsAg (7). The properties of such vaccines
arc the subject
,. of this report.
HEPATms B V ACCINE DERIVED FROM A

HEPATOCELLULAR CARCINOMA CEU LINE
Alexander and co-workers (8) recovered a continuous line of HCC cells (PLC/
PRF/.5: Alexander cell line) in culture from a cancer patient who was also an
HBsAg carrier. These cells, grown in vitro, secrete HBsAg but no infectious virus
(9). The immortality of such cells offere d an alternative source or HBsAg but the
yields grown in conventional culture were too small to be considered feasible
economically (10-JJ). McAleer and colleacues (6,U). in our laboratories, adapted
the Alexander cells to irowth in Vitafibcr pseudoc:apillary units. In this S)'Stem,
the Alexander cells are propagated in the interstices of bundles of semipcnneable
membrane capillaries through which the erowth medium is circulated. Maximal
VIRAL HEPATITIS and LMR DISEASE Copyright e 1984 by Grune & Str1non
ISBN o«J89-1g-]8-5 All righla of N1production in any t~ ,~ .
H1 11eM&n R, Buynak ER. rkus HZ, 1gett r RZ, cAl eer t.JJ, ~clean AA, et . al .
Control of Hepat1t1s B virus infection: Vacc1n s produced frcmi Gl ex1nd er
cell 11n nd frOlil r ecombin1nt yeast cel l cultures. In : Vy&s GN, Di enstag
JL, Hoofnasile JH, eds. Vir1 l Hep11t1t1s and LiveF Dhe11s • Orlando:Grune
and Statton. 1984 : 307-14 .
01058
308 Hilleman, Buynak, Markus, et al
fl&. 22.1. Hepatitis B surface anti,en panicles purified rrom Alexander hepat~inoma
cell culture l!luid.
yields of HBsAg were obtained in the fiber bundle units under conditions that
lowered celJular metabolism. This consisted of lowerina the temperature of incu-
bation to 32•c with the addition of 10-• molar caffeine to the circulatina medium.
Such cells could be maintained for periods up to a year, with periodic harvest of
fluid that contained an amount of HBsAg equal to that of some human plasmas.
The HBsAg was readily purified from the cell culture fluid by immune affinity
chromatography followed by diaestion with pepsin and DNase.
Figure 22. J shows purified HBsA1 particles. that were indistinguishable mor-
phologically from those that were purified from human plasma. Panicles obtained
from plasma were essentially identical in aJI measurable aspects to those purified
from AJexander cell fluids. The particles were 22 nm in diameter; the ultraviolet
absorption spectra were the same; and the E"' and the HBsAg to protein ratios
were alike.
Purified HBsAg derived from Alexander cells was treated with formaldehyde
and was fonnulated into vaccine (6) by absorbing 20 ~• of HBsAe to each ml of
aluminum hydroxide suspension containin& 0.5 mg of aluminum and addin& t :20.000
concentration ofthimerosal as preservative. The vaccine was proved safe in tests
in four chimpanzees that were aiven aqueous material by the intravenous route.
The vac:c:ine was assayed for immunizina potency in mice by a standardized
extinction dilution assay and was compared with pl&sma-derived vaccine. Table
22.1 shows that the 50% extinction dose, ED,., was nearly the same for both
vaccines and the geometric mean titers were comparable. It is evident that the
HBsAg produced in HCC cells is indistinguishable in potency from that derived
from plasma. · ·
New HBV Vaccines 309
Table 22.l
Mouse Potency of HBsAg Vacc:ine Prepared in Alexander Cell
Cuhure Compared with That Prepared from Human Plasma
Alexander Cell Vaccine Plasm, Vaccine Lot 799-l
Vaccine No. mice G.M. No. mice G.M.
(~&) positive/total Titer- positive/total Titer
JO &'JO l'431 8/10 1729

2.S MO 504 9/10 1204
0.625 7/10 74 4/10 8
0.156 0,/9 <8 0/10 <8
ED,.t 0.79 0.81
•Geomeuic mcan cilcr.

tOose ~uired lO seroconvert ~ of mice.
Two penons who were initially seronegative for hepatitis B virus markers
and who had advanced central nervous system cancer were 1iven two primary
doses of vaccine a month apart and a booster dose 6 months after the initial
irtjection. The findings shown in Table 22.2 revealed that both patients developed
antibody to HBsAg (anti-HBs) in low titer. Three persons, two of whom were
given only the primary doses and one of whom was ,iven all three doses of vaccine,
but were lost to follow-up. demonstrated no anti•HBs response. The slow and
relatively low antibody responses to the HCC cell-derived vaccine were similar to
those in other immunosupprened persons who were given vaccine of human
plasma origin. The vaccine was well tolerated in all the subjects.
Table 22.J
Findinas in Two Cancer Patients wbo Received Alexander Cell-
Produced Hepatitis B Vaccine at Time 0, I, and 6 Months
Titer-
Months after Vaccination
Observation Patient Pre•vaccinet 2 3 6 7
Anti-HBs 717-C <I < 8 I 16 16 l6
-6 < I < 8 <8 ND <8 36
HBsA 717-C
-6
Anli-HBc 717-4
-6
AST 717-4 IS 25 16 24 16 14
-6 9 7 8 NO 9 6
ALT 717-4 19 23 24 21 22 18
-6 2, 20 20 ND 17 12
"Titer i, upnssed in uniu. NO m no dc1,mnina1ion; - ., below 1hc limit o( de1ect~n.

17 ays prior 10 IW\Ulll vaccinalion.
01060
310 Hilleman, 8uynak, Markus, et al
-!'1'11"~~:3:!!.~.-i,
fl&. ll•.2. Hepatitis B surfact anti1en panicles purified from recombinant yeast cell cul-
ture.
Careful attention was given to the matter of safety of the vaccine, considering
its oriein from human liver cancer cells. The methods used for treatment in puri-
fying the HBsAg and the DNA-destructive processes aimed at viral and cellular
nucleic acids that were used to prepare the vaccine were of such efficiency as to
delete any possible oncogenic DNA that might have been theoretically present in
the starting fluid.
Joint efforts between our laboratories and those of W. Rutter and B. Hall led
to the preparation of vectors carrying the DNA sequence for HBsAg (7,/$). The
HBsAg was of subtype adtt• and was produced in fermentation cultures of Soc-
charom'JIU:S cutvisiot carrying the vector and employing yeast alcohol dehydro-
genasc J as the promoter. HBsAg was released from the cells by homogenization
and was purified by immune affinity chromato,raphy (16).
Electron microscopy of yeast-derived HBsAg, as shown in Figure 22.2, revealed
a homoeeneous array of panicles free of extraneous morphologic entities. The
ultraviolet absorption spectrum was the same as for plasma-derived HBsAg with
an E"' of "15. The SDS-polyacrylamide gel elcctropboretic pattern under reducing
conditions shown in Figure 2~.3 revealed a sin&le band at 23.000 daltons (23K)
corresponding lo the nonglycosylated polypeptide of HBsA1 derived from plasma.
The purified HBsAg was formulated into vaccine by adsorbing to aluminum
hydroxide adjuvant to contain 40 ~ of HBsAJ protein and 0.5 mg aluminum per
010f>1
2 3 4
. .. .; .. -: ..-••ia .' ,
. . ..
.
.. : ··-.:..
: ~.
~? ~-,~'.·:?~!f-:
~~',:f:t'.\.:-_:.._:~: _
fie. 22.3. SDS-polyacryltmide 1el electrophoresis of puri-
fied Alexander cell (lane 2) and yeast-derived (lane 3) hepatitis
B surface antisen. Lane I contains molecular weisht stan-
dards and lane 4 contains clarified yeast extract before puri-
fication.
dose. The standardized extinction mouse potency test, shown in Table 22.3,
demonstrated that the yeast-derived HBsAg was at least as potent as plasma-
. derived antigen based on the 50% utinction dose (ED,o) and the geometric mean
titen.
Table 22.4 shows that Jrive t monkeys also developed antibody following
vaccination with the yeast-derived antigen. A single injection at all dose levels
resulted in seroconversion of all the animals in both yeast and plasma vaccine
groups. High antibody titers were maintained for more than a year.
Protective efficacy was tested in challenge experiments with susceptible chim-
panzees. In the tests shown in Table 22 ..S. four chimpanzees were given three I-
ml iruections of the adw subtype yeast-derived vaccine I month a part and four
animals were held as unvac:cinatcd controls. One month after the third dose of
vaccine wa s 1iven, two. vaccinated and two control animals were challenged
intravenously with adr subtype virus and the other four vaccinated or unvaccinated
animals we re challe nged with ayw subtype virus. All the vaccinated animals devel-
oped antibody followin1 immunization and all were solidly protected..aiainst the
virus with all serologic a nd histopathologic markers remaining neptive . Protection
01062
312 Hilleman, 8uyn11k, Markus. et al
Table 22.l
Antiaenic Potency in Mice ofHBsAg Purified from Yeast and from
Human Plasma
Anti•HBs response after
HBsAa dose
vaccination
per irtjeciion
Vaccine Source (p.& protein) No. pos.frotal GMT
Human Plasma JO 9110 563
Lot 799-2 2.S 10/10 2235
0.625 C.19 32
0.156 0/10 4
ED. 0.639
Yeast co 10/10 5432
Lo18l--t 10 10/10 ~
~s 1/)0 673
0.625 1/10 %7
ED. < 0.625
was afforded irrespective of HBsAa subtype. The findina or subtype cross-protec-
tion is consistent with the presence of the common a anti1en detenninant present
in all hepatitis B virus subtypes (17.18). That this common a antigen suffices to
protect against all subtypes was c:onftnned recently in clinical studies ( 19) in which
HBsAg/ad vaccine protected renal dialysis staff against type HBsAg/ay exposures.
Qinical studies of the yeast cell-derived vaccine have been initiated by our
group. The early findines indicate most favorable antibody responses in man that
are being reponed elsewhere in this symposium (Abstr. SAT. LA 50 and chapter
23).
CONCLUSION
The evolution in our laboratories of a fiber bundle-cncineered culture system
for production of HB,Aa by Aleu.nder HCC cells presents a simple and practical
means for hepatitis B vaccine preparation. However. the more recent develop-
Table 22.,
Anti,cnic Potency in Grivet Monkeys of HBsAg Purified from
Yeast and from H1&n1&n Plasma•
Anti-HBs response after initial vaccine dose
HBsAg dose
(Geometric mean titer)
Vaccine per il\iection
Source (~S protein) WeekC Week8 Week ll Weel; ,2
Human plasma 10 l6 213 170 127
Lot 86016 2., 343 6227 173<18 9924
0.62' 53 '642 ll6' 5688
0.156 IS 128 83 358
Yeast
Loi 11-C
40
10 184
88 1078
m
7103
1489
m,"
C984
2., 225 1168 6361 .
0.62' 109 925 ,18 I~
•Vaccine Biven a1 lime Oand 4 weeks.

01063
Table ll.5
Protective Efficacy of Purified Yeast HBsAg Vaccine
Challen,e
Result
AST&
Anti-HB, HB,Ag ALT Liver
Vaccine Chimp Titers Subt)'JIC HBsA1 Anti-HBc Elevations Patholon
Yeast
· Vaccine I 1830 adr 0 0 0 0
2 S40 odr 0 0 0 0
3 18300 trJW 0 0 0 0
◄ 7200 ay•· 0 0 0 0
Controls 5 < 8 odr + + + +
6 <8 odr + + + +
7 < 8 4JYM' + + + +
I <I "Y"'' + + + +
ment. by our group, of HBsAg production in recombinant yeast cells appears to
offer advantaees that exceed those of the Alexander cell system. The most impor•
tant advantaaes of the recombinant vaccine relate to simpler HBsAc production
by yeast cells in fennentation tanks and removal of any lingering apprehensions
about wety of vaccine derived from a human cancer cell source. ·
Human plasma-derived hepatitis B virus vaccine is limited by the supply or
plasma and the technic:al complexity of the process to assure safety and efficacy.
Alternative technolQiies developed in our laboratories include production from
(a) hepatoc:ellular carcinoma c:ells (Alexander cell line: PLC/PRF/S) cells in culture,
and (b} from recombinant yeast carrying a high expression vector for hepatitis B
surface antigen (HBsAg) gene subtype odiv. HBsA, was purified mainly by affinity
chromatography and formulated on alum adjuvant. The polypeptide dimer of
HBsAg produced in Alexander cells was identical to that from plasma; the yeast•
derived dimer was not glycosylated but was otherwise the same. Both vaccines
were as potent as plasma vaccine in mice and both were highly immunogenic when
tested in humans. The subtype adw yeast vaccine was aJso highly immunoaenic
for monkeys and pvc solid protection in chimpanzees a,ainst challense with
hctcrol010us subtype odr and ayM' viruses. Vaccine prepared from yeast offers a
means for simplified production of HBsAg in fenncntation tank culture and does
not bear the stigma of cancer cell oriain or
Alexander cell vaccine. Recombinant
yeast-derived HBsAa shows 1rcat promise for simplified mass production or hep-
atitis B vaccine.
REFERENCES
I. Hilleman MR.. BertJand AU, Buynak EB, et al. Oinical and laboratory studies or
HBsAg vacc,ne. In Vyas GN, Cohen SN. Schmid Reds. Viral Hepatitis. Philadelphia,
Fmiklin Institute Press, 1978:S25-S37.
2. Hilleman MR. Buynak EB. Mc:Aleer WJ, et al . Hepatitis A and hcpatiti, B vaccines.
In Szmuncss W , Aller H, Maynard J eds. Viral Hepatitis. 1981 Interna tional Sympo-
sium. Philadelphia, Franklin ln5titute Press, 1982:38.S-397. ·
010btl
314 Hilleman, Buynalt, MQrkus, et al
3. Buynak EB, Roehm RR, Tytcll AA, ct al. Vaccine apinst human hepatitis B. JAMA
1976: 235:2832-213...
41. Adamowicz P. Gerfaux G. Platel A. el al. Larae scale production or an hepa1i1is B
vaccine. In Maupas P, Ouesry P eds. Hepatitis B Vaccine. lNSERM Symposium No.
18. Amsterdam, Elsevier/Nonh-Holland Biomedical Press, 1981:37-49.
5. Coutinho RA. Lclie N, Albrech1-Van uni P, ct al. Efficacy or a heat ;nactivatcd
hepatitis B vaccine in male homosexuals: outcome of a plac:ebo controlled double
blind trial. Br Med J 1983; 286:llOS-1308.
6. McAlecr WJ, Markus HZ, Wampler DE, et al. Vaccine apinst human hepatitis B
virus prepared from anti1en derived from human hepatoma cells in culture. Proc Soc
Exp Biol Med l9M; 175:314-319.
7. McAleer WJ, Buynak EB. Mai1etter RZ. et al. Human hepatitis B vaccine from
recombinant yeast. Nature 19&4; 307:178-180.
8. Alexander J, Macnab G. Saunders R. Studies on in viiro production of hepatitis B
surface anti,en by a human hepatoma cell line. In Pollard M ed. Perspectives in
Virology. New York. Raven Press, 1978:103-120.
9. Tabor E, Copeland JA, Mann GF, et al. Nondetection of infectious hepatitis B virus
in a human hepatoma cell line producin& hepatitis B surface an1i1en. ln1er-..ir0Joay
1981: 15:82-86.
10. Macnab OM, Alexander JJ, Lccatw 0, et al. Hepatitis B surface anti1en produced
by a human hepatoma cell line. Br J Cancer 1976: k:509-51.5.
I I. Skelly J. Copeland JA. Howard CR. et al. Hepatitis B surface anti&en produced by 1
human hepatoma cell line. Nature 1979; 282:617-611.
12. Copeland JA. Skelly J, Mann GF, et al. Hepatitis B surface antigen production as a
vowth cyclc•related terminal event in PLCJPRF/S hepa1oma cells. J Med Virol 1980;
.5:257-264.
13. Dacmer RJ, Feinstone SM. Aleunder JJ, ct al. PLC/PR.FIS (Alexander) hepatoma
cell line: funhercharacterization and studies ofinfectivity. Infect lmmun 1980: 30:607-
611.
14. McAlecr WJ, Markus HZ. Bailey FJ. et al. Production of purified hepatitis B surface
anti1en from Alexander hepatoma cells 11own in artificial capillary units. J Virol Meth
1983; 7:263-271.
IS. Valenzuela P, Medina A. Rutter WJ, et al. Synthesis and assembly of hepatitis B virus
surface anliJCfl particles in yeast. Nature 1982; 298:347-350.
16. Wampler DE, Buynak £B. Harder BJ, et al. Hepatitis B vaccine purification by
immune affinity chromato,raphy. In Chanock R. Lemer R eds. Modem Approaches
to Vaccines. Cold Spring Harbor. Cold Sprina Harbor Laboratory. 19~. in press.
17. Purcell RH. Gerin JL. Hepatitis B subunit vaccine: a preliminary repon of safety and
efficacy ccsr.s in chimpanzees. Am J Med Sci 197.5; 270;39~399.
18. Barker LF, Maynard JE, Purcell RH. et al. Viral hepatitis. type B. in experimencal
animals. Am J Med Sci 1975; 270:189-195.
19. Szmuness W, Stevens CE. Harley EJ. et al. Hepatitis B vaccine in medical staff' of
hemodialysis units. N Enal J Med 1981: 307:I.C8l-l486.
01065
Jou.mol of the H0118 Kone Medical ~ n , Vol.87, No. 2, 1986.
east
Vaccine
MAURlCE Jl. lllLLEMAN, ROBERTE. WEIBEL & EDWAllD /Ji. S()(}LIVJCK
ABSTRACI'
Tht human hrpatitis B 11GCcine of plasma or;,in prepared by 011r loborotor~, Ml performed well with rerpect to ,afety,
immuno,enicity and protretiue r(fic,cy. Th, uacciM ha. now ~,n u•d in about 2 million persons u,oridwide. The m:enl
dtmon1tration of HTL V-ITJ or LAV l>irW • pula/iue ro/r in AIDS and ill ,w,dy inacti1.1Glion t:,y tht 1ttp1 u,rd in INJCCint pr-oduction
lull rvnoutd thr llllt lui,erin, doubts about safety from thl! dondpoinll of JJDS in relation to pl4'nuM1triutd IICICcinc.
TIit limit in 6Ul)ply of haman h,patitil B carmr
pllwna ond the Mtd lo opp/y hi;ily technical procedures for purificaaon and
inactwotion itim11/otcd th, ,eelrin, of an allemattvr ,ourc, of antigen from y«ut t>«zrtn, tht surface an«,m 1rne. Preliminary
dl,t,, indicate tlw,t lht recombinant 1H1Ccinr prepared t:,y our lal>orotoriu Ital lhown at INII 1quioaltnt immuna,enicity for onimoll
·111 wdl a, lulmon adults and children co,npared with plo,mo-demd uoccine. The 1111,wen in the 11GCcinc is hithly purified and
coiuu no clinically important rNCtiona. Eilhtern lot, of 1111ecine lw,ue bttn p ~ d to dat, and liceNUn u up«ted durin8 /au
1986.
Key,,or : Recombinont Hepatitis B uacclnt - ,_,, - immurao,enictty - 1W1Ctiona
PLASMA VACCJNE T■blt l

Human bepatttll B c1111 bt raadDy conlrolled by propbylac-
tlc Yacclnatlon. UNGM4 "ftnt ,enentlon" TaCCID• prepared Present: l'IMna-derlftd bwn■n bepatitll B uccine
lllinf 111rfact 111tl,en purlfted from tbe plum• of hepatitis B
cmlen have been procluct d In ...,eza1 countria (1-5). And,-11 IOIUff! Pi■-na of h-■11 bep■tltia 8 carrlen.
Vaccine prepared In our -laboatorla <-
Tlble 1) -
Preparation: Ellenti■lly pun surface antlten.
Uc.n•d for ,enn distribution In 1981. 'lbil ,aeelne hal
pert-eel very well. 111, Yll:Clnt consllta of -,n11a11y pun lnactinUon by S dlffennt methom,
aurface ut11ea that la !ranted by 3 dttennt lnactlntlon applied aequentillly.
procedures wblcb are NqVtntlally applied ud which an
deslped to deltroy all mlcrobllll llfe form,. 'lbt fteClne lncorpontect.ln alum adjuunt.
lncorpontecl Into alum adjuunt Induces bapatltla B utlbody >9~ of DOrmal c:hDdml and aduUa
In mon tban 961. of nclplsnta, DYnall, and affords men Uwl clenlop antibody after 3 doNa.
95~ protection aplnat b. .litla B In upaaed nonuJ pmo111
(8 ). Al uiay be up91:&ed, the qcclne la I• effecUff In i,-nom >9R prot«tlon ln nonnal ptDOIII.
whOII 11Dmu111 ,y,te_ 8N! Jmmuaoddlcient or are lmmuno-
Leta effectlff In lmmvnodeDc1111t or
suppNWd. Lea than especPCS antibody reepOlllell ban been ilnmun01Upp1 -d p,nons.
reporwd in 1101nt lituatlom of u• (7,8). hnestlptlon b•
mealed that IUCh lower antibody IIIPOIIIII may occur Ill Duration of Immunity ill not known. It II
penom In wbom tbe qccine wu injected into tbe bllttocb llao unlmcnrn when late booater dCIIIS of
rather tban iDto tbe arm. Vacclnr pen in tbe bUttocb may Yllldne mlpt bf needed.
ran frequently to rncll mlllde and be depmlted lllltead Into
Tuwtta: hnom of dltftnld blp risk. Especially
lat wtme It may ftOt be well moblllltd (9).
lnfanll born to eamer motben In hill!
pl'nll- UNI.
Bnntually Ill penons.
Safety and
...,. __ ,,,..,...a-k,_..,._......., Extnt of Uee: ~.600,000 ca. dlatributed.
_...,.._.....,,._.._lNN,U.L\. >2,000,000 penons reeelftd 'flleelne to
- I I. 1111-. 1'11. D .. D. le. date.
Mw... 11. - k . 1 1.Il.
~-,--.u.-,,.,....,.... ..... ., .........

, _ _ . . . , . . . , . _ lllN. U.L\.
'lbe •acclne la ale,
concerm.
ineludlnr AIDS
1<1..,;i11. - l . l l.Il.
Cc:.r za •••••to:Dr,....._&,KINau
,._..It ..... 1-.....,.,,Go.A. __ ..,
JUI AUllll-lllillcC..I_ , Ho,elili,- - -
lllud,U,IN•
75
0!066
~ombinAnt Yeast Human Hepatitis B Vaccine.
The duniuon of protective efllccey followlns vaccination Is contact in n11t11n (11) u well IIS In prol'iding l'flident actin
not )lnown but, 11S ahown in Fl111n 1, the IJ'Bt majority of immunity. Because immunity aplast hepatitis B infection·may
penona (39/'4) retain utlbody for at least 4-5 years (lff 6). be present at antibody ln'ell Im than de&eclable in the
The 3-dole repneo for Immunization, atvinl the booster dole labonitory, and because or the pbenomtnon of anamnestic
at 6 monthl after the Initial dote, Is biSIIIY efrectlTe in priming recall, It may be premature (12) to project wben late booster
the immune system for npld anamnestlc immune recall on immunizations mllbt be needed.
laur contact with viral ant11en on nvaecination (10) or 011
vaccine 100¾
4096
2048 ii i100%-
1024
512
89%
Geometric
256 ,L.._ 91%
V -If--'>
128
Mean Titer
(Ausab Units)
84
32
16 % =o/o Seropoaitive
8
4
2
0
Time Following I I
i
Vaccination (months)
Number of Persons
0 3
65 65 656564
67 9 18
55
2,
60
36
57
' 48
44
f'ilure 1
Antibody denlopment and penistence In adults wbo recel•ed 3 1a11 of hepatltl1 B Yacclne (study 665).
The .-lne has been talpwd mainly for 111t In apecial infected pl.ma and by the need lo apply blply technical
r,roups a t' high rid: &o hepatitis B. Prelently, added emphula Is procedum for purification and lnricUTatlon of poalble
bein, p,n &o pff'fffltlq infl!Ctlon In newbon lnfanll born to inftcUOUI apntl that mipt be pmtnt ill lllCh plllllll.
curter motbm in blply encllmlc populatlo111 IIICb II ID S.C.U.. of thia, alternatln 1011rces of antiJta wtre 10111ht and
Eutern Alla and Africa. Enmually, all 111eceptlble penona two pnettc recombl111Dt antl,eru baff been 1Utd In our
IDIIY be •aceluted. More than ~.5 mWion doaee of the ftOCilcle labolll.torieu (19-21). One ot th-, the Callier Alnandtr
have been diatrlbuted and more than 2 mmton penom ban hepatoc:uctnoma elll (22) ls a reeomblnant of natun. The
recelYed oM or IDONI doMI or tbe TICCin• to date. other, obtained by clo!WI(! the ,-n, of hepatitis B 111rfaee
Conctm hal been 1Jq1.-d for poalblt trammllllloa of ant!IH ln&o yeut (28), II quite unllDtUial.
aeq11ired Immune delcitney dilellt (AIDS) by lmplOPfily AICUllldu h,pGtOCfftlno,no celL Veeclne (19) prepared
prepared bll)l&ICil B 'flCCIIMI liDct thf IDtillD ii obCalntd rrom antlten IICllted from the bepetocuemoma cella pown
frolll hwu.n pluma. RtlloTIIIINI of tbe HTLV-m or I.AV In cultun lnlUllly pJO'flCl 'tltfY aUIICUH bom the standpoint
,n,up han now been lho'll'll (13-17) to be tbe Dkeiy c11111e for of yield and lmmunlllna potency, but It ... el'idtnt that a
tbil blood and body IICfftloa-~ltted dlmae. 'l1leN Yaccint dnl'f9d fnllD a n o n ~ IIO\llft would be more
1111111 an nadDy lnactl'flted and deatroyed by the P10CeE acctp&ablt. Hepatltll B neclne pNpand ulln, anti,-n obtain-
UJed to prwpare tb1 TaeclM (18), 11'11111 dlrlct ffidtntial proof ed from tltlltr lrlllafonDed or flullly neopJaatlc hWIWI or
tor the safety or the ncclne flom the atandpolnt or "AIDS anilllal cell• an DOt likely &o bt accapt.ct by llclDalna author!•
•lrln". Utt and tbe mecllcal pioffllion, ttptelllly llnct tht antlpns
llEOOMBINANT YEAST VAOCINE CID be rude efflcltnUy ID ncomblnant yeu& ctlla.
The production ot human bepatltla B 'QCClne flom tbe Hepatitu B _.,_ 1111ff,wn prcptll'Gtfo11 in recombined
human pluma 1011rce Is limited by Ult nlllablt 111pply of yeo,t. Joint ,ttoru betw•n our laboaatori" ud tboae of Dn.
76
01067
Journal of the Hong Kone Medicail Auocimtion, Vol. 37, No. 2, 1985.
Rutter and Hall of the Universities of California and Washlnc- Fi1111n 3, consists o( the hepatitis B surface anU,en eene
ton led to the preparation or a recombinant yeut cell system flanked on one side by a promoter (llyceflldehyde 3.p
tor producine hepatitis B antieeo (23). Fi,un 2 mows the dehydroeenase l, ADH-1), both bein1 esaential to proper
principal defined areas or the hepatitis B cenome The eene translation of the surface anti1en. The mt of the nucleic acid
retion that encodes the hepatltli B 111rfact anti1en, but not the in the plasmid Is needed to achieve Its functions in the yeast
''pre-S" (24) or the core antisen, was inserted into a suitable cell syawm and to serve as a marker (yeut leucine 1ene l for
vector and was lmplanced into ordinary Baker's yeast or pl'IM!nce or the plumld ID yeut cell,. The con,uu~t employed
SOfcharomyca cenu;.ilu. The plumid constNct, shown in subtype Adw surface antipn ,ene.
PRE-5 ANTIGEN
(163 Amino acids)
HEPATITIS B
..,. SURFACE ANTIGEN
(226 Amino acids)
HEPATITIS B HEPATITIS B VIRUS DNA:

CORE ANTIGEN
LONG STRAND
(183 Amino acids)
- - SHORTSTRAND
Fisun 2
Hepatitis B virus 19nome and defined antigens Chat an produced.
77
01068
Recombinant Yeast Human Hepatitis B Vaccine.
HEPATITIS B SURFACE ANTIGEN GENE
ADH-1 TERM INATOR

GAPDH PROMOTER
----.., ---........ ... ,
',
''
I /\,
L.1
4.__---- E. coli DNA ,
f (PBR-322, Ampicillin ~
: resistant)
Yeast Leucine-2
Gene
--cto
Fiture 3
Construct of plasmid (pHR~GAPM 7 /33) used to produce hepatitis B 111rface 11\tittD In y-t.
'l'be hepatitis B 111rfact antigen pioduced in yeat is clll• inclYlduals that react• with antlren encoded in the pre•S repon
uaoc:iatff. Surface anttaen wu nleued from tbe yeut celb by (28-30) but It ii not known 1riltther such antibody 1n1y pll)' a
hoinopniUtlon, the purirlc11tlon wu achlned malllly by role in protectin immunization. Tkoupi sugl!ltions of lht
silica, hydrophobic interaction (bUtyl &prOA) and pl eac:lu• lmportuce of pre-S repon in aenerating full immunity to
sion cbromatopapbia. 'lbe hepatltia B •rface antis• IUed In hepatitia B ba'ft been made (31), thla statement Is not 111pport-
the vaccine comi1u of polypeptida that lff identical ID -ino td by tbe known ICilntUlc nldellce llld the publillled Uteri·
acid MqU•- to tbOR of hWD&D p l - - - but laeldna tun (321, Indeed, 'f10Clna without p~S an•o have been
llyeosylation. 1bt llycoayl groups are not nquired for PIOYed blpily tfftctlYI In inducing Ulllllllnity aplnst hepatitis
immun011nieity. Other mH1Ur11blt physical, cbtmlcal, and B In the extemiYe cliniclll and field atudits carried out during
inununolop:al attributes of die yeas&-dlr1,ed vaccine an the peat aennl yean (6,33-34). It is quite clear that there are
subltantillly the aame u tbOllf of the antlpn pnpared from many lmmunolopc determl11a11ta or epitopet within lbe
bUlll&II plllllll&, collection of viral utipna productd under the total of lht
N stated abon, tbe ncombin&Dt bepatitil B surfece Viral 11neue code. 'lbe fllltltlon mlpt be Iliad or bow 111111y
1nti11n vaccine dots not contain COft antlpn. e antipn, or dUfnent 1Pltopel an netcltd or 01&1bt to be Included in the
antiseo from tilt ao-called "pre-S" regioc (aee F'qun 2). YaDeine: 'nie • antlpa epltopa of the surface antlpn 1ft quite
Antibody ap1111t con antlp n and perhapa apilllt e anu,en adlquate to afford IOlld and luting protection apimt hepatl•
iuy provide at leut putlal protection apimt hepatitis B ,1ru1 til B and there ii praently no .evident need or benefit to be
inftetion (25-27). Antibody has been clemonstrnted in infected derived from increulng the clllt or complexity of the vaccine
by a ddl1111 antipm 111cb u tbOII frGm the pre-S region.
78
OlO&Q
Jouml of tbe Hong Kong Medk:nl Astocilltion, Vol. 37, No. 2, 1985.
F1111n4
Electron miCJOll'IPh of purified hepatitis B 111rfaee uu,en derived from yeut recombinant cells
(Lot C1,Y52-1, ma,niflcation 156, 750X)
The hepatitis B 111rface antiren parddes produced In y- t uay, u shown In Table 2, lhowtd tbe y-t-derlved Tacclae
cells, shown In fi111re 4, an morpholop:ally similar &o Uioee &o btat leut u potent II pluma-dtrlted enti1en belled on
isolated from human P'-• thoup the mean particle 1ize of comparbon of &he ~ extlnc:tlon dole (EDH) and the
the former may be llilhtlY smaller. geometrie mean tlten.
Hepatitis B 11C1Ccine prrpared from recombi111111t Y•t-
derivtd mrf.:e ontifcn.
The purified antiltn wu formul■te4 Into v■ccllle by
adsorblnc to aluminum bydrHldt adjuftllt to contain 10 111
of anti1en and 0.5 mi alumln11111 per 1 ml vaccine doee.
Potency - y by the standard extinction mouat potency
7g
01070
Recombinant Yeast Hum11n Hepatitis B Vaccine.
Table 2
Ant~enlc poteney In mtee of HBoAa purified from yeast and from human pllllllmn
Anti-HBIAI respome aft.er vaccination

Vaccine Source Antilen Doe2 ~r illj5ctlon (Ill! protein)
no. pos./to&III GMT
Human plasma 10 9/10 563
Lot 799-2 2.5 10/10 2,235
0.625 4/9 32
0.156 0/10 4
EDso 0.639
Yeast 40 10/10 5,432

Lot81-4 10 10/10 3,400
2.6 8/10 673
0.626 8/10 967
ED,o <0.625
Chimpanzea liven yeut ncombinant bepatitla B ,recclne In mabn remainlna neptln. 'l'he h1p11titbs B aurface anti,en
suitable repmen dfl'elop antibodift and are protecled apimt contains the a antigen common to all subtypes plus the d and
inftetion on challenae with live hepatltil B \'inu. In the !Nb w subtype deutnniDIDts. Protection wa& ,inn lll&inst heter-
summarized In Table 3, four chlmpomees wtn Jh'•n three oio,oua 111btypes odr 1111d cryw, abowtnc the acwquacy or the
intram1191:Ul&r injections of Yaeclne containing 40 'Ill of antlpn broad 11pee1JUm II tpltopes in the ncomblnant antl19n to
per ml dcJle at monthly 1Dtm1al1. One month after the third protect aplnat the beterolCJIOU• subtype&. Tbe llndln1 or
dose was ,inn, 2 •acclnlted and 2 control anillllll were htterolotoas subtype protection wit.II ncombinant-deri•td
challen,ed intravenoully With beterolOl(IUI 11/r lllbtype YINI vaccine ii cona!ICtllt with the Ondinp with plum-derived
and a simil,ar INJUP of anilllala wtre cb'1Jenpd with beleroloa· vaccina obtained in ■tudlea In anlmlla (3~6) and in clinical
oua ayw 111btype YiN&• .All the nccinat.ed anilllala cleYeloped atudla (34) In wblcb Nbtype tld vaccine protecwd renal
antibody follo'Win« immunization and all were aollcly protect- dialysis 1tatt worken apinst Ill btype oy challeng,.
ed 11ainat the virus with all serolollc and hlltopatholOIIC
Table 3
Protectm .mcaey or purified JN1t 1Dtian YICdDe

Cballeap
Antibody
Clllmp Re9pollll a.■alt
&o
HJleA&! An~ Anti- Euyme LiYft
(Hll&Ag) HBcA( Elnaliolln Patboloa
Yeut
Vaccine 1 1,830 Adr 0 0 0 0
2 540 Adr 0 0 0 0
3 18,300 Ayw 0 0 0 0
4 7,200 Ayw 0 0 0 0
C.Ontrol, 5 <8 Adr + + + +
6 58 Adr + + + +
7 <a Ayw + + + +
8 <8 Ayw + + + +
80
01071
Joumal of the Hone Koll( Ml!dical Aaociation, Vol. 37, No. 2, 1985.
Clinkal tests in human bei/'111. Studies in human subjects or complaints such as headDChe, fatirue a nd malal1t have bttn
the recombinant yeat vaccine hue been initiated for purpose stated by a 1n1all pen:entace of veccinees.
of m.asurin& antibody rHponses and for demonstrating Prior atudles establilbed (6 ,3:1-34) the relationship between
protective efflcaey. About 1500 persons of divene •1e, sex, antibody rnponR lo vaccina tion and immunity to bepatitis B.
and health status, and reosraphlc -idence have received Thouri, any new vattine rnust stand on its own merits, it is
vaccine to date. There were no important clinical reactions Instructive to compare the aerolOlic responses in human bein,s
attributed to vaccination. Mild soreness at the Injection site to the widely uaed plasma -derived ,accine prepared in our
h~ been reported in 19% or
recipients and othu minor laboratories with th01e to the new recombinant preparation.
Time Following First Dose Of Vaccine {Months)
1 2 3 6 7 9
100
90
80
C Vaccine
0 70 Given At
...
"iii
Q) 60 0. 1. 6 Months
>
C
0
50
0
...
0
CD
40
en 30
if-
20
10
0
. . z<
al al D..0..0 0.. Q. Q. Q. 0.. Q D. Q. 0 Q. 0.. 0
Q) E E C11 0 CII
0
0 0 CII CIIOCII
°'◄ CII Cl
"' Cit CII
◄ ◄ ::a ◄ ◄ ::i ◄ ◄
- ... 0◄
C: =t =I :::i ◄ :I.
uu al al
ii: ii: °'
0=-
000
N .- .-
0 0
N .-
0
.- ~ ......
0 0 N
0 0 0
N ... ...
0 0
1G
> ~
0
01
::i
0
...
N
Fl,un 5
S.rolOlic ft1110ll$H to 3 doles of pl111111 (20 Ill or 10 µg) compared With recombinant (101,11) Yacciue in adults
Fipre 5 llhowa the Rl'Olotic ftndiap In a compGlite of liven 10 Ill yeast vaccine compared With 10 14 or 20 µs
studies carried out by our laboratoria to compare the anti• plasma vaccine per dow were nearly alike. Most important,
body lffPOIIRI in adult penons to 3 doles of plasma-derived 87% of the. 111bjecta had deYelopecl antibody within 1 month
vaccine at 20 or 10 JAi antlp n per dole wltll tbat of tht followiq Injection of the 1eeond dole of y-t-clerlved ftCCine
recombinant vecclne at 10 ,q Pff dole. Data were Crom 400 to (I-month llleedlnc) and tllil wu lncreued to 96-99% by 1 or 2
800 au bjecb per n ccint ,roup. All ncclnes were p ven intra• months followiDI the booa&er dOR clttn at 6 moatha.
muscularly by the mne rt,unen at time 0, 1 and 6 months.
The rate and rapidity of antibody aeroconvmlon in peno111
01072
Recombinant Yeast Human Hepatitis B Vaccine .
Time Following First Dose Of Vaccine (Months)

1 2 3 6 7-8
G.M.T.•
(SIN Ratio) 20 19 37 37 79 52 51 94 63 141 164
25 38 42 124
,oo "GMT •
Geometric
90 Mean Titer
Vaccine
80 Given At
C: 0. 1 & 6 Mos.
0 70
...
iii
GI 60
-46-56
Persons
> Per Group
C:
0 50
.
0
0
GI
(/)
40
30
0~
20
10
0
z<
a. a.
z<
CII Q Q lL Q 0 Q 0 CL. Q C
CD E
C: 0 Q 0
CII
::i
Q
::i
at
:i.
Q
:i. ~! 1:1'>
::i
Q
:i.
Q
:i. "'
=I
Q
:i.
Cl
=I
ij
i
>
CII
a:
Cl
:i.
Cl
-
:i.
0
CD
::i
II)
~
0 in C
N ...
0 It) 0
N ~
It) C
N
-
0 It)
flluft 6
Seroloflc - ~ to 3 dolet or pluma (20 111) compand with neomblnaat (10 Ill or 5 111) vaccines In 21-30 year.old
penou (adapted from DaVldaon 1111d Knicman, LAllcet 1: 108, 1985).
Similar ftndlnp, 111111mariztd In Flpn 6, wtre oblalned In

1tudift canled out In 21-30 year old adults by Dnldaol! and
KNpun (31) In which rates for seroconnnloa, and btilha
of antibody following 20 Ill dole p1llllla Yltdnt wtn COlllpU•
ed with 10 1-11 or 5 Ill etc- ynat •111:elne. n- authon
su111ested that tbe les81!r antibody , . . , _ lo ytat ncom-
binant VIICCine reported by .m1 et Ill. (38) mleht ban been
related to the IIDIIII aum ben of iadi'fichials includtd la that
study.
82
01073
Joumal ol Ille Hq iCon8 .Mlecliclll Alllociation, Vol. 37, No. 2, 1985.
Time Following First Dose Of Vaccine (Months)
1 2 3 6 7
100 Persons :
90 DNA · 21 To
28 Per Group
80 Plasma. 62
C
0 70 Vaccine
...
ui
Q)
60 Given At
0, 1 & 6 Mos.
>
C: 50
0
u
...
0 40
Q)
m as
en 30
iii ;;
# 0 0
20
10 z
0
z0
0
., a. 0 0 a. 0 0 Q. 0
IP
C
.
E
Ill z< z<
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F1111re 7
Serolopc: respomes to 3 doles of pl1111111 (10 #II) compared with recombinant (5 pg or 2.5 111) Yaccin• in chiidren· 1-11
yeanofaae.
Studies to meuure antibody nspoma in children and technolOI)'. It II anllclpated that the yeut vaccine will be
infants an In P'°lfflL Ooly limited ftndinp are uailablt to llctnstd in tbe U.S.A. and other countri• by late 1985 and
date and tbeee an from ,cu& clfflfll out by our poup ID 1· that tbe vacd11e will be anllable for renen1 distribution in
to ll•YHr old children. F'lfllre 7 lhows th• 1erolOC1c m p - early 1986. In anticipation of tbt de•llopmenl ol 111ch
In tll- children, to 3 dONS of plalma-dmvtd 'flCCint ll•en In rec:omblaant vacclA•, tbe World Healtb Orpnlzl&lon CODYen-
10 JIC doN (62 chDclnn) compued with ytaat recombinant •d a poup ol expena durtnc Nonmber of 1984 who wrote tbt
Yaecine liven In S.0 J1C or 2.S 14 dole (21 and 28 clllldrtn ptr pro'fillcmal requlnmeats for the 1tandard1Zation and control
poup, rt1pectlnlyt. 'lbt rnponaeg wer. eaenti.Uy equlnlenl or' hepatltl1 B necine made by ncomblnant DNA techniquea
in all Jl'OIIP', tboutb It must bt noted that tbe nwnben of In y-t. 'lbne requb:emenu should bt made final btfon the
lndividulb pwn 'fllCCIDt lff anal.I. end of 1985 111d abould proYide I bull for worldwide l'tfllll•
tory control of hepatitis B Yaccine produced In ncomblnant
CONCLUDING 11.IMARKS y•tclll&.
It is clnr, wt believe, Chat tht pla&ma-dtdnd hepatitis B
•aecine bu perfonntd in u exemplary way and has pro'1dfll 1 Acbowleclpmeat:
means for lncucln1 Immunity, with safety, epimt human 'nit authon ant indebted to Dr. 0.Yid ,. Weat, Ph. D.,
hepaUUs B vlnu Infection. 'lbt DeCftllty for deftlopinr • M.P.H. and to Dr. Barbara A. Zajac, M.D., Ph. D. for the
subltl&ute but equally Ntiafllc&ory YICCine, Jne from the med diDlcal mpome dllta.
for human pl111111 and technolop:ally limpler to produce, lull
beeo accompliahtd by the application of y-t nc0111binanl
83
01074
Recombinant Yeast Human Hepatitis B Vaccine.
REFERENCES 17. Sompdharan, MG; PopoYic, M; Bruch, Let al: Antibodies

1. Buynat. EB; Roehm, RR; Tytell, AA et al: V1eeioe reactive with hwnan T-lymphotropic retroviruses (HTLV-
11ainst human hepatitis B. Journal oC the American III) in the serum of patients with AIDS. Science 1984;
Mlldict.1 AsT.ociatiOI\ 19'16; 7.35: 2837.-2834 . 224: r,O{,-r»08.
2. Hilleman, MR; &rtlood, AU; Buynak, EB et al: Oinical 18. CDC: Hepatlti& B vaccine: Evidence confinninc lack of
and laboratory studies of H&Ag vaccine: in: Vyas, GN; AIDS tr■mmlulon . Morbidity and Mortality Weekly
Cohen, SN and Schmid, R (F.ds) Viral Hepatitis, pp. 525- Report 1984; 33: 68S-687.
537 (The Franklin Institute Press, Philadelphia 1978). 19. Mc:Aleer, WJ, Markus, HZ; Wampler, DE et al: Vaccine
s: Adamowi4%, P; Gerfaux, G; P\atel, A et al: l..aqer 11Cale ,pinst lluman hepatiti, B YiNs prepu.d hom anti1en
dtrlvtd from h11111811 bepatoma Ctlll In culture. Proeeed-
production oC an hepatitia B YaCCine; in: Maupu, P ud
Guesry, P (Eds) Hepatitis B Vaccine. INSERM Sympo- inp of the Society Cor Experimental BioloCY and Medi-
sium No 18, pp. 37-49 (Elsevier/North-Holland Biomedi- cine 1984; 175: 314-319.
cal Presr., New York 1981). 20. Mc.Aleer, WJ; Buynek, EB: MaiJetter, RZ et al: Human
4. Hilleman, MR; Buynak, EB; McAleer, WJ et al: Hepatitia llepallt11 B •accine from recombinant yeast. Nature 1984;
A and hepat.it.il JI vaccines; in: Szmuneu, W; Alter, Hand 307: 178-180.
Maynanl, J (Eds) Viml HepatitiL 1981 lntematlODlll 21. Scolnict, EM; McLean, AA; West, DJ et al: Clinical
Syinposium, pp. 386-397 (The Franklin lnl&itute Pre11, euluation In healthy adults of ■ bepatiti, B YICCioe made
Philadelphia 1982). by ncomblnant DNA. Journal of the American Medical
5. Coutinho, RA; Lelle, N; Albrecht-Van Lent, P et al : Auoclatlon 1984; 251: 2812-2815 . .
ECricacy of a heat inactivated hepatitis B 'taccine in male 22. Alexmder, J; Macnab, G ■nd S.unden, R: Studies in /n
hom01txuD1s: ou&come or a placebo controlled double Vitro production or hepatitis B surface ant!pn by a
blind trllll. British Medical Journal 19&3; 286: 1305 buman hepaioma cell line; in Pollard, M (U) Penpectlves
-1308. ID VlroloCY, Vol 10, pp. 103-120 (Rann l'rffg, New York
6. Samunes&, W; Stnena, CE; Zani, EA et al: A cona-olled 1978).
clinical trial of the emcacy of the hepatitia B Yaccine 23. Valenzuela, P; Medina, A; Rutter, WJ et al: Syntheaia and
(Heptavax B): A final report. HepalOloCY 1981; 1: 377- auembly of bepatiti1 B viN1 surface ■nt11en partlclK in
385. yeut. Nature 1982; 298: 347-350.
7. Schutt, DM; Lender, M; Snedeker, Pet al: Hepatitis B 24. 1'olllil, P; Dejean, A; Brecbot, C et Ill: Structure of
vaccine in a hospital. Annals or lnwmal Medlcint 191M; bepatlt.is B YINS DNA; in: Vyu, GN; Dlemtag, JL and
101: 702-721. ffoofnaele, m (&Is) Viral Hep■t1t11 and Llnr Dlleut,
8. Strickler. AC; Klhley, PC and Vellend, H: Seroconvenion pp. 4M5 (Grune i. Stnttoa, Orlando 1984).
rates with hepatitis B vaccine. Annals of lntemli Medicine 25. Tabor, E ■nd Gerety, RJ: Poulble role of immune
1984; 101: 564. JtSP011M1 to hepaUtia B core antiJen in protection ■clinst
9. COO Suboptimal mpoue to hepatitis B Y&CCine pven by bepatitia B lnf1et10111. Lancet 1984; 1: 172.
injection into the buttock. Morbidity and Mortality 26. Mumy, K; Bnlct, SA; Hinnen, A et al: Hepatitis B Ylr,is
Weekly Report 1985; 34: 10~108, 113. antietns made in microbial cells immunise a,lllnst Yin!
10. Hilleman, MR: Vaccines aplmt vlnl hepatitis. Intern&· infection. F.mbo .bimal 19&4; 3: 645-650.
tional R.Yie• of the Anny, Navy and Air Fon:e Mriical 27. Stephan, W; Prince, AM and Brotman, B: Modulation oC
Services 1984; 57: 11-2'. bepatlti1 B Infection by lntnvenous application of an
11. Stevem, CE; Taylor, PE; Tone, MJ et al: Hepatitis B immUnoClobulln prepantion that conLalm antlbodiH to
vaccine: an oveniew; in: Vy•. GN; I>lensta,e, IL and bepatltla B e and core ant11ena but not to hepatitis B
Hoofn■sle, JH (Eda) Viral Hepatitis and Liver Dileut, surface antlpn: Journal or Virology 1984; 51: 420-62-4.
pp. 276-291 (Gnine & Strltion, Orlando 191M). 28. Neuratb, AR; Kent, SBH and Strict, N: Location ■nd
12. Jils, W; Schmidt, M; DeinhwdL, F et al: HepatlCII B chemic■! syntheai1 of a pre.S 1eae coded lmmunodmlnant
vaccination: How lo111 does protection lut? t.ncet 1984; epilOpe of hepatitis B Yln,a. Science 1984; 224: 393-394 . .
~45~ . 29. Ha,rmann, KH; Goldmann, U; Schwmu, W tt al: Lu,..
13. Vilmer, E; Rouzioux, C; Vninet Bnin, F et Ii: Isolation .urface proteins of bepatltu B l'ini1 contatnin1 the pre-S
of new lymphouopic rettcmn11 [rom two liblln&S With Mqlltnct, Joumal of ViroloCY 1984; 62: 396-602..
haemophilia B, one with AIDS. Lancet 1984; 1: '163-757. 30. Machida, A; Kiahimoto, S; Ohnum■, H et al: A hepatitis B
14. PopoVic, M; Sam,adbaran, MG; Rnd. E et al: Detecdon, surface anlipn polypeptide (P31) with the receptor for
isolation, and continuous procmcuon or cytopathlc polymerized bWDID u well as chimpanzee albumins.
retroYiNMS (HTLV-W) from patients with AIDS and GutroenllrolOIY 1983; 85: 268-274.
pre-AIDS. Science 1984; 224: 497-500. 31. Walpte, R: Hepatitis B. Taiwan plan& mus vaccination.
15. Gallo, RC; Salabuddin, SZ: l'oporic, M et Ii: Frequent Nature 191M;Sl2: 190.
detection and isolation of cytopathlc retroviruses (HTLV- 32. Hilleman, MR: ViNs ftetina. Nature 1985; 313:

Recombivax HB Clinical Trial

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Recombivax HB Clinical Trial

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TABLE OF CONTENTS

Vol ume Starting

II. lllTllune Affinity Vaccine 00052

III. 6 2f Vaccine 1 00121

a. Individual Study Sumnary

Reference No. 85-053 Drug Licensed Name: Hepatitis B Vaccine

Hepatitis B Vaccine (Recombinant), RECOMBIVAX HB, is a non-infectious subunit

I. INDICATIONS FOR USE:

RECOMBIVAX HB is indicated for immunization against infection caused by

RECOMBIVAX HB will not prevent hepatitis caused by other agents such as

Vaccination is recommended for those persons who are or will be at

II. DOSAGE AND ADKIRISTRATIOH:

RECOMBIVAX HB consists of hepatitis B surface antigen which is produced

contains 10 mcg of hepatitis B surface antigen adsorbed onto 0 . 5 mg of

Primacy vaccination consists of three injections of vaccine, with the

III . MANUFACTURING A.ND CONTROLS:

A. MANUFACTURING A.ND CONTROLS

The organism, Saccha romyces cerev1s1ae, strain (b)(4)

The final container is tested for sterility, general safety,

The manufacturer submitted for evaluation samples and protocols of

The recoawended storage temperature of the vaccine, adsorbed onto

The product will have an expiration dating of twenty-four months at

The major equipment used in the manufacture and filling of the

The package insert (copy attached) contains appropriate statements

A pre-license inspection of the MSD biological production facilities

F. ENVIRONMENTAL IMPACT ANALYSIS REPORT

An environmental assessment for the manufacture and use of

IV. PHARMACOLOGY, BIOCHEMISTRY AUD SEROLOGY:

RECOKBIVAX HB is composed of HBsAg which is the product of a plasmid

Serological studies have been perfonned to evaluate the anti-HBs

An inhibition assay using a monoclonal antibody that had been shown to

Avidity constants against entire HBsAg ranged from 4 to 8 x 1010 in

Comparison of the proportions of the anti - a and anti- d components of the

These serological studies show that although the antibodies induced by

Hepatitis B virus is one of several viruses (hepatitis A, hepatitis.

In the United States and Northern Europe, hepatitis B virus infects

Hepatitis B surface antigen is the main component of the outer

Antibodies to HBsAg (anti-HBs) have been shown to be protective

From July 1983 to January 1986 RECOMBIVAX HB was administered to

The vaccine was administered as a series of three intramuscular

Vaccine recipients were asked to report their temperature and any

Post-vaccination blood samples were obtained for the determination

The vaccine was proven non-infectious for man in a human safety

RECOMBIVAX HB has been well tolerated. There have been no

In the clinical trials, no cases of anaphylaxis, severe

The frequency of clinical complaints reported within five _days

Clinical studies have demonstrated that Hepatitis B Vaccine

Anti-HBs responses of 511 healthy adults 20- 69 years of age, 83

Antibody response to the vaccine is age dependent. The younger

Preliminary data from a double - blind. randomised, controlled

recombinant vaccine and 93~ (38/41) for the plasma-derived

The protective efficacy of RECOMBIVAX HB has been demonstrated

VI. ADVISORY PANEL CONSIDERATION.

Data concerning the manufacture, safety and efficacy of Hepatitis B

VII. APPROVED PACKAGE INSERT

A copy of the approved package insert is attached. (Exhibit 1)

Ira Berkower, M.D.

PERSONS INCLUDED IN CLINICAL STUDIES OF HEPATITIS B

Health Care Personnel/ Other 2414

FREQUENCY OF CLINICAL COMPLAINTS WITHIN 5 DAYS FOLLOWING

FREQUENCY OF CLINICAL COMPLAINTS WITHIN 5 DAYS FOLLOWING

FREQUENCY OF CLINICAL COMPLAINTS WITHIN 5 DAYS FOLLOWING

FREQUENCY OF CLINICAL COMPLAINTS WITHIN 5 DAYS FOLLOWING

ANTIBODY RESPONSES AT 7/8 MONTHS AMONG HEALTHY INDIVIDUALS