HEPATITIS B VACCINE
DESCRIPTION:
Engerix-B (Hepatitis B Vaccine (Recombinant)) is a noninfectious recombinant DNA
hepatitis B vaccine developed and manufactured by SmithKline Beecham
Biologicals. It contains purified surface antigen of the virus obtained by
culturing genetically engineered Saccharomyces Cerevisiae cells, which carry the
surface antigen gene of the hepatitis B virus. The surface antigen expressed in
Saccharomyces Cerevisiae cells is purified by several physicochemical steps and
formulated as a suspension of the antigen adsorbed on aluminum hydroxide. The
procedures used to manufacture Engerix-B result in a product that contains no
more than 5% yeast protein. No substances of human origin are used in its
manufacture.
Engerix-B is supplied as a sterile suspension for intramuscular administration.
The vaccine is ready for use without reconstitution; it must be shaken before
administration since a fine white deposit with a clear colorless supernatant may
form on storage.
Each 1 mL of vaccine consists of 20 mcg of hepatitis B surface antigen adsorbed
on 0.5 mg aluminum as aluminum hydroxide. Each 0.5 mL of vaccine consists of 10
mcg of hepatitis B surface antigen adsorbed on 0.25 mg aluminum as aluminum
hydroxide. Both formulations contain 1:20,000 thimerosal (mercury derivative) as
a preservative, sodium chloride (9 mg/mL) and phosphate buffers (disodium
phosphate dihydrate, 0.98 mg/mL; sodium dihydrogen phosphate dihydrate, 0.71
mg/mL).
ACTIONS/CLINICAL PHARMACOLOGY:
Several hepatitis viruses are known to cause a systemic infection resulting in
major pathologic changes in the liver (e.g., A,B,C,D,E). The estimated lifetime
risk of HBV infection in the United States varies from almost 100% for the
highest-risk groups to approximately 5% for the population as a whole. (REF. 1)
hepatic necrosis, chronic active hepatitis and cirrhosis of the liver. Sixty to
80% of neonates and 6 to 10% of adults who are infected in the United States
will become hepatitis B virus carriers. (REF. 1) It has been estimated that more
than 170 million people in the world today are persistently infected with
hepatitis B virus. (REF. 2) The Centers for Disease Control (CDC) estimates that
there are approximately 0.75 to 1.0 million chronic carriers of hepatitis B
virus in the United States. (REF. 1) Those patients who become chronic carriers
can infect others and are at increased risk of developing primary hepatocellular
carcinoma. Among other factors, infection with hepatitis B may be the single
most important factor for development of this carcinoma. (REF. 1,3) Considering
the serious consequences of infection, immunization should be considered for all
persons at potential risk of exposure to the hepatitis B virus. Mothers infected
with hepatitis B virus can infect their infants at, or shortly after, birth if
they are carriers of the HBsAg antigen or develop an active infection during the
third trimester of pregnancy. Infected infants usually become chronic carriers.
Therefore, screening of pregnant women for hepatitis B is recommended. (REF. 1)
Because a vaccination strategy limited to high-risk individuals has failed to
substantially lower the overall incidence of hepatitis B infection, both the
Immunization Practices Advisory Committee (ACIP) and the Committee on Infectious
Diseases of the American Academy of Pediatrics (AAP) have endorsed universal
infant immunization as part of a comprehensive strategy for the control of
hepatitis B infection. (REF. 4,5) These advisory groups further recommend broad-
based vaccination of adolescents. The ACIP, AAP, American Academy of Family
Physicians (AAFP) and American Medical Association (AMA) recommend routine
vaccination of adolescents 11 to 12 years of age who have not been vaccinated
previously.(REF. 6) The AAP further recommends that providers administer
hepatitis B vaccine to all previously unvaccinated adolescents.(REF. 7) (See
INDICATIONS AND USAGE.) There is no specific treatment for acute hepatitis B
infection. However, those who develop anti-HBs antibodies after active infection
are usually protected against subsequent infection. Antibody titers >/=10 mIU/mL
against HBsAg are recognized as conferring protection against hepatitis B. (REF.
6) Seroconversion is defined as antibody titers >/=1 mIU/mL.
Immunogenicity In Healthy Adults And Adolescents: Clinical trials in healthy
adult and adolescent subjects have shown that following a course of three doses
of 20 mcg Engerix-B given according to the ACIP recommended schedule of
injections at months 0, 1 and 6, the seroprotection (antibody titers >/=10
mIU/mL) rate for all individuals was 79% at month 6 and 96% at month 7; the
geometric mean antibody titer (GMT) for seroconverters at month 7 was 2,204
mIU/mL. On an alternate schedule (injections at months 0, 1 and 2) designed for
certain populations (e.g., neonates born of hepatitis B infected mothers,
individuals who have or might have been recently exposed to the virus, and
certain travelers to high-risk areas. See INDICATIONS AND USAGE.), 99% of all
individuals were seroprotected at month 3 and remained protected through month
12. On the alternate schedule, an additional dose at 12 months produced a GMT
for seroconverters at month 13 of 9,163 mIU/mL.
Immunogenicity In Adolescents: In clinical trials with healthy adolescent
subjects 11 through 19 years of age, immunization with 10 mcg using a 0, 1, 6-
month schedule produced a seroprotection rate of 97% at month 8 (N=119) with a
GMT of 1,989 mIU/mL (N=118, 95% confidence intervals=1,318-3,020). Immunization
with 20 mcg using a 0, 1, 6-month schedule produced a seroprotection rate of 99%
at month 8 (N=122) with a GMT of 7,672 mIU/mL (N=122, 95% confidence
intervals=5,248-10,965).
Immunogenicity In Neonates: Immunization with 10 mcg at 0, 1 and 2 months of age
produced a seroprotection rate of 96% in infants by month 4, with a GMT among
seroconverters of 210 mIU/mL (N=311); an additional dose at month 12 produced a
GMT among seroconverters of 2,941 mIU/mL at month 13 (N=126).
Immunization with 10 mcg at 0, 1 and 6 months of age produced seroconversion in
100% of infants by month 7 with a GMT of 713 mIU/mL (N=52), and the
seroprotection rate was 97%.
Clinical trials indicate that administration of hepatitis B immune globulin at
birth does not alter the response to Engerix-B.
Immunogenicity In Children: In clinical trials with 242 children ages 6 months
to, and including, 10 years given 10 mcg at months 0, 1 and 6, the
seroprotection rate was 98% 1 to 2 months after the third dose; the GMT of
seroconverters was 4,023 mIU/mL.
Immunogenicity In Older Subjects: Among older subjects given 20 mcg at months 0,
1 and 6, the seroprotection rate 1 month after the third dose was 88%. However,
as with other hepatitis B vaccines, in adults over 40 years of age, Engerix-B
vaccine produced anti-HBs titers that were lower than those in younger adults
(GMT among seroconverters 1 month after the third 20 mcg dose with a 0, 1, 6-
month schedule: 610 mIU/mL for individuals over 40 years of age, N=50).
Hemodialysis Patients: Hemodialysis patients given hepatitis B vaccines respond
with lower titers, (REF. 7) which remain at protective levels for shorter
durations than in normal subjects. In a study in which patients on chronic
hemodialysis (mean time on dialysis was 24 months; N=562) received 40 mcg of the
plasma- derived vaccine at months 0, 1 and 6, approximately 50% of patients
achieved antibody titers >/=10 mIU/mL. (REF. 7) Since a fourth dose of Engerix-B
given to healthy adults at month 12 following the 0, 1, 2-month schedule
resulted in a substantial increase in the GMT (see above), a four-dose regimen
was studied in hemodialysis patients. In a clinical trial of adults who had been
on hemodialysis for a mean of 56 months (N=43), 67% of patients were
seroprotected 2 months after the last dose of 40 mcg of Engerix-B (two X 20 mcg)
given on a 0, 1, 2, 6-month schedule; the GMT among seroconverters was 93
mIU/mL.
Protective Efficacy: Protective efficacy with Engerix-B has been demonstrated in
a clinical trial in neonates at high risk of hepatitis B infection. (REF. 8,9)
Fifty-eight neonates born of mothers who were both HBsAg and HBeAg positive were
given Engerix-B (10 mcg at 0, 1 and 2 months) without concomitant hepatitis B
immune globulin. Two infants became chronic carriers in the 12-month follow-up
period after initial inoculation. Assuming an expected carrier rate of 70%,
(REF. 1) the protective efficacy rate against the chronic carrier state during
the first 12 months of life was 95%.
Other Clinical Studies: In one study, (REF. 10) four of 244 (1.6%) adults
(homosexual men) at high risk of contracting hepatitis B virus became infected
during the period prior to completion of three doses of Engerix-B (20 mcg at 0,
1, 6 months). No additional patients became infected during the 18-month follow-
up period after completion of the immunization course.
Interchangeability With Other Hepatitis B Vaccines: Recombinant DNA vaccines are
produced in yeast by expression of a hepatitis B virus gene sequence that codes
for the hepatitis B surface antigen. Like plasma-derived vaccine, the yeast-
derived vaccines are protein particles visible by electron microscopy and have
hepatitis B surface antigen epitopes as determined by monoclonal antibody
analyses. Yeast-derived vaccines have been shown by In Vitro analyses to induce
antibodies (anti-HBs) which are immunologically comparable by epitope
specificity and binding affinity to antibodies induced by plasma-derived
vaccine. (REF. 11) In cross absorption studies, no differences were detected in
the spectra of antibodies induced in man to plasma-derived or to yeast-derived
hepatitis B vaccines. (REF. 11)
Additionally, patients immunized approximately 3 years previously with plasma-
derived vaccine and whose antibody titers were <100 mIU/mL (GMT: 35 mIU/mL;
range: 9-94) were given a 20 mcg dose of Engerix-B. All patients, including two
who had not responded to the plasma-derived vaccine, showed a response to
Engerix-B (GMT: 5,069 mIU/mL; range: 624-15,019). There have been no clinical
studies in which a three-dose vaccine series was initiated with a plasma-derived
hepatitis B vaccine and completed with Engerix-B, or vice versa. However,
because the In Vitro and In Vivo studies described above indicate the
comparability of the antibody produced in response to plasma- derived vaccine
and Engerix- B, it should be possible to interchange the use of Engerix-B and
plasma-derived vaccines (but see CONTRAINDICATIONS).
A controlled study (N=48) demonstrated that completion of a course of
immunization with one dose of Engerix-B (20 mcg, month 6) following two doses of
Recombivax HB(R)* (10 mcg, months 0 and 1) produced a similar GMT (4,077 mIU/mL)
to immunization with three doses of Recombivax HB (10 mcg, months 0, 1 and 6;
2,654 mIU/mL). Thus, Engerix-B can be used to complete a vaccination course
initiated with Recombivax HB.
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* yeast-derived, Hepatitis B Vaccine, MSD.
*/* plasma-derived, Hepatitis B Vaccine, MSD.
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INDICATIONS AND USAGE:
Engerix-B is indicated for immunization against infection caused by all known
subtypes of hepatitis B virus. As hepatitis D (caused by the delta virus) does
not occur in the absence of hepatitis B infection, it can be expected that
hepatitis D will also be prevented by Engerix-B vaccination.
Engerix-B will not prevent hepatitis caused by other agents, such as hepatitis
A, C and E viruses, or other pathogens known to infect the liver.
Immunization is recommended in persons of all ages, especially those who are, or
will be, at increased risk of exposure to hepatitis B virus, (REF. 1) for
example:
Health Care Personnel: Dentists and oral surgeons. Dental, medical and nursing
students. Physicians, surgeons and podiatrists. Nurses, Paramedical and
ambulance personnel and custodial staff who may be exposed to the virus via
blood or other patient specimens. Dental hygienists and dental nurses.
Laboratory and blood-bank personnel handling blood, blood products, and other
patient specimens. Hospital cleaning staff who handle waste.
Selected Patients And Patient Contacts: Patients and staff in hemodialysis units
and hematology/oncology units. Patients requiring frequent and/or large volume
blood transfusions or clotting factor concentrates (e.g., persons with
hemophilia, thalassemia, sickle-cell anemia, cirrhosis). Clients (residents) and
staff of institutions for the mentally handicapped. Classroom contacts of
deinstitutionalized mentally handicapped persons who have persistent hepatitis B
surface antigenemia and who show aggressive behavior. Household and other
intimate contacts of persons with persistent hepatitis B surface antigenemia.
Infants, Including Those Born Of HBsAg-Positive Mothers Whether HBeAg Positive
Or Negative (See DOSAGE AND ADMINISTRATION.)
Adolescents (See ACTIONS/CLINICAL PHARMACOLOGY.) Subpopulations With A Known
High Incidence Of The Disease, such as: Alaskan Eskimos. Pacific Islanders.
Indochinese immigrants. Haitian immigrants. Refugees from other HBV endemic
areas. All infants of women born in areas where the infection is highly endemic.
Persons Who May Be Exposed To The Hepatitis B Virus By Travel To High-Risk Areas
(See ACIP Guidelines, 1990.)
Military Personnel Identified As Being At Increased Risk.
Morticians And Embalmers.
Persons At Increased Risk Of Disease Due To Their Sexual Practices, such as:
Persons with more than one sexual partner in a 6-month period. Persons who have
contracted a sexually transmitted disease. Homosexually active males. Female
prostitutes.
Prisoners.
Users Of Illicit Injectable Drugs.
Others: Police and fire department personnel who render first aid or medical
assistance, and any others who, through their work or personal life- style, may
be exposed to the hepatitis B virus.
Adoptees from countries of high HBV endemicity.
Use With Other Vaccines: The Immunization Practices Advisory Committee states
that, in general, simultaneous administration of certain live and inactivated
pediatric vaccines has not resulted in impaired antibody responses or increased
rates of adverse reactions. (REF. 12) Separate sites and syringes should be used
for simultaneous administration of injectable vaccines.
CONTRAINDICATIONS:
Hypersensitivity to yeast or any other component of the vaccine is a
contraindication for use of the vaccine. Patients experiencing hypersensitivity
after an Engerix-B (Hepatitis B Vaccine (Recombinate)) injection should not
receive further injections of Engerix-B.
WARNINGS:
(See CONTRAINDICATIONS.)
Hepatitis B has a long incubation period. Hepatitis B vaccination may not
prevent hepatitis B infection in individuals who had an unrecognized hepatitis B
infection at the time of vaccine administration. Additionally, it may not
prevent infection in individuals who do not achieve protective antibody titers.
MULTIPLE SCLEROSIS: In persons with multiple sclerosis, stimulation of the
immune system may induce an exacerbation of the disease. Consequently, in
persons with multiple sclerosis who have not been previously infected with
hepatitis B as demonstrated by serologic absence of immunity, the benefit of
immunization must be weighed against the risk of exacerbation of the disease.
PRECAUTIONS:
GENERAL As with any percutaneous vaccine, epinephrine should be available for
use in case of anaphylaxis or anaphylactoid reaction.
As with any vaccine, administration of Engerix-B should be delayed, if possible,
in persons with any febrile illness or active infection.
PREGNANCY Pregnancy Category C: Animal reproduction studies have not been
conducted with Engerix-B. It is also not known whether Engerix-B can cause fetal
harm when administered to a pregnant woman or can affect reproduction capacity.
Engerix-B should be given to a pregnant woman only if clearly needed.
NURSING MOTHERS It is not known whether Engerix-B is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
Engerix-B is administered to a nursing woman.
PEDIATRIC USE Engerix-B has been shown to be well tolerated and highly
immunogenic in infants and children of all ages. Newborns also respond well;
maternally transferred antibodies do not interfere with the active immune
response to the vaccine. (See ACTIONS/CLINICAL PHARMACOLOGY for seroconversion
rates and titers in neonates and children. See DOSAGE AND ADMINISTRATION for
recommended pediatric dosage and for recommended dosage for infants born of
HBsAg-positive mothers.)
ADVERSE REACTIONS:
Engerix-B (Hepatitis B Vaccine (Recombinant)) is generally well tolerated. As
with any vaccine, however, it is possible that expanded commercial use of the
vaccine could reveal rare adverse reactions.
Ten double-blind studies involving 2,252 subjects showed no significant
difference in the frequency or severity of adverse experiences between Engerix-B
and plasma-derived vaccines. In 36 clinical studies a total of 13,495 doses of
Engerix-B were administered to 5,071 healthy adults and children who were
initially seronegative for hepatitis B markers, and healthy neonates. All
subjects were monitored for 4 days post-administration. Frequency of adverse
experiences tended to decrease with successive doses of Engerix-B. Using a
symptom checklist,** the most frequently reported adverse reactions were
injection site soreness (22%) and fatigue** (14%). Other reactions are listed
below.
INCIDENCE 1% TO 10% OF INJECTIONS
Local Reactions At Injection Site: Induration; erythema; swelling.
Body As A Whole: Fever (>37.5 deg C).
Nervous System: Headache**; dizziness.**
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** Parent or guardian completed forms for children and neonates. Neonatal
checklist did not include headache, fatigue or dizziness.
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INCIDENCE <1% OF INJECTIONS
Local Reactions At Injection Site: Pain; pruritus; ecchymosis.
Body As A Whole: Sweating; malaise; chills; weakness; flushing; tingling.
Cardiovascular System: Hypotension.
Respiratory System: Influenza-like symptoms; upper respiratory tract illnesses.
Gastrointestinal System: Nausea; anorexia; abdominal pain/cramps; vomiting;
constipation; diarrhea.
Lymphatic System: Lymphadenopathy.
Musculoskeletal System: Pain/stiffness in arm, shoulder or neck; arthralgia;
myalgia; back pain.
Skin And Appendages: Rash; urticaria; petechiae; pruritus; erythema.
Nervous System: Somnolence; insomnia; irritability; agitation.
Additional adverse experiences have been reported with the commercial use of
Engerix-B. Those listed below are to serve as alerting information to
physicians.
Hypersensitivity: Anaphylaxis; erythema multiforme including Stevens-Johnson
syndrome; angioedema; arthritis. An apparent hypersensitivity syndrome (serum-
sickness-like) of delayed onset has been reported days to weeks after
vaccination, including: arthralgia/arthritis (usually transient), fever and
dermatologic reactions such as urticaria, erythema multiforme, ecchymoses and
erythema nodosum (see CONTRAINDICATIONS).
Cardiovascular System: Tachycardia/palpitations.
Respiratory System: Bronchospasm including asthma-like symptoms.
Gastrointestinal System: Abnormal liver function tests; dyspepsia.
Nervous System: Migraine; syncope; paresis; neuropathy including hypoesthesia,
paresthesia, Guillain-Barre syndrome and Bell's palsy, transverse myelitis;
optic neuritis, multiple sclerosis. (See WARNINGS); seizures.
Hematologic: Thrombocytopenia.
Skin And Appendages: Eczema; purpura; herpes zoster; erythema nodosum, alopecia.
Special Senses: Conjunctivitis; keratitis; visual disturbances; vertigo;
tinnitus; earache.
Potential Adverse Experiences: In addition, certain other adverse experiences
not observed with Engerix-B have been reported with Heptavax- B(R)*/* and/or
Recombivax HB. Those listed below are to serve as alerting information to
physicians:
Urogenital System: Dysuria.
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* yeast-derived, Hepatitis B Vaccine, MSD.
*/* plasma-derived, Hepatitis B Vaccine, MSD.
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DOSAGE AND ADMINISTRATION:
Injection: Engerix-B should be administered by intramuscular injection. Do Not
Inject Intravenously Or Intradermally. In adults, the injection should be given
in the deltoid region but it may be preferable to inject in the anterolateral
thigh in neonates and infants, who have smaller deltoid muscles. Engerix-B
should not be administered in the gluteal region; such injections may result in
suboptimal response. The attending physician should determine final selection of
the injection site and needle size, depending upon the patient's age and the
size of the target muscle. A 1-inch 23-gauge needle is sufficient to penetrate
the anterolateral thigh in infants younger than 12 months of age. A 5/8-inch 25-
gauge needle may be used to administer the vaccine in the deltoid region of
toddlers and children up to, and including, 10 years of age. The 1-inch 23-gauge
needle is appropriate for use in older children and adults. (REF. 13)
Engerix-B may be administered subcutaneously to persons at risk of hemorrhage
(e.g., hemophiliacs). However, hepatitis B vaccines administered subcutaneously
are known to result in lower GMTs. Additionally, when other aluminum- adsorbed
vaccines have been administered subcutaneously, an increased incidence of local
reactions including subcutaneous nodules has been observed. Therefore,
subcutaneous administration should be used only in persons who are at risk of
hemorrhage with intramuscular injections.
Preparation For Administration: Shake Well Before Withdrawal And Use. Parenteral
drug products should be inspected visually for particulate matter or
discoloration prior to administration. With thorough agitation, Engerix-B is a
slightly turbid white suspension. Discard if it appears otherwise. The vaccine
should be used as supplied; no dilution is necessary. The full recommended dose
of the vaccine should be used. Any vaccine remaining in a single-dose vial
should be discarded.
Dosing Schedules: The usual immunization regimen (see Table 1) consists of three
doses of vaccine given according to the following schedule: 1st dose: at elected
date; 2nd dose: 1 month later; 3rd dose: 6 months after first dose.
There is an alternate schedule with injections at 0, 1 and 2 months designed for
certain populations (e.g., neonates born of hepatitis B infected mothers, others
who have or might have been recently exposed to the virus, certain travelers to
high-risk areas. See INDICATIONS AND USAGE.). On this alternate schedule, an
additional dose at 12 months is recommended for infants born of infected mothers
and for others for whom prolonged maintenance of protective titers is desired.
In infants born of mothers who are not hepatitis B infected, Engerix-B may be
administered at birth, 1 month of age and 6 months of age.
TABLE 1
Group Dose Schedule*
Infants born of:
HBsAg-negative mothers 10 mcg/0.5 mL Usual
HBsAg-positive mothers 10 mcg/0.5 mL Either
Children:
0 through 10 years of age 10 mcg/0.5 mL Either
Adolescents:
11 through 19 years of age 10 mcg/0.5 mL Usual
20 mcg/1.0 mL Either
Adults (>19 years) 20 mcg/1.0 mL Either
Adult hemodialysis 40 mcg/2.0 mL** 0, 1, 2, 6 months
* Usual dosing schedule is 0, 1, 6 months; alternate dosing schedule is
0, 1,2, 12 months. When the alternate schedule is used for adolescents,
the 20 mcg/1.0 mL dose should be used.
** Two x 20 mcg in one or two injections.
For hemodialysis patients, in whom vaccine- induced protection is less complete
and may persist only as long as antibody levels remain above 10 mIU/mL, the need
for booster doses should be assessed by annual antibody testing. 40 mcg (two x
20 mcg) booster doses with Engerix-B should be given when antibody levels
decline below 10 mIU/mL. (REF. 1) Data show individuals given a booster with
Engerix-B achieve high antibody titers (See ACTIONS/CLINICAL PHARMACOLOGY.)
Booster Vaccinations: Whenever administration of a booster dose is appropriate,
the dose of Engerix-B is 10 mcg for children 10 years of age and under; 20 mcg
for adolescents 11 through 19 years of age and 20 mcg for adults. Studies have
demonstrated a substantial increase in antibody titers after Engerix-B booster
vaccination following an initial course with both plasma- and yeast-derived
vaccines. (See ACTIONS/CLINICAL PHARMACOLOGY.)
See previous section for discussion on booster vaccination for adult
hemodialysis patients.
KNOWN OR PRESUMED EXPOSURE TO HEPATITIS B VIRUS: Unprotected individuals with
known or presumed exposure to the hepatitis B virus (e.g., neonates born of
infected mothers, others experiencing percutaneous or permucosal exposure)
should be given hepatitis B immune globulin (HBIG) in addition to Engerix-B in
accordance with ACIP recommendations (REF. 1) and with the package insert for
HBIG. Engerix-B can be given on either dosing schedule (see above).
REFERENCES:
1. Centers for Disease Control: Protection against viral hepatitis:
recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR.
39(No. RR-2),1990. 2. Robinson, W.S.: Hepatitis B virus and the delta virus. In
Mandell, G.L., Douglas, R.G., Bennett, J.E. (eds): Principles And Practice Of
Infectious Diseases, vol. 3, New York, John Wiley & Sons, 1990, pp. 1204-1231.
3. Beasley, R.P., et al.: Efficacy of hepatitis B immune globulin for prevention
of perinatal transmission of hepatitis B virus carrier state: final report of a
randomized double-blind, placebo-controlled trial. Hepatology 3:135-141, 1983.
4. Centers for Disease Control: Hepatitis B virus: a comprehensive strategy for
eliminating transmission in the United States through universal childhood
vaccination: recommendations of the Immunization Practices Advisory Committee
(ACIP). MMWR. 40(No. RR-13):1-25, 1991 5. Committee on Infectious Diseases:
Universal hepatitis B immunization. Pediatrics 89(4):795-800,1992. 6. Ambrosch,
F.: Persistence of vaccine-induced antibodies to hepatitis B surface antigen--
the need for booster vaccination in adult subjects. Postgrad. Med. J. 63(Suppl.
2):129-135, 1987. 7. Stevens, C.E., et al.: Hepatitis B vaccine in patients
receiving hemodialysis. N. Engl. J. Med. 311:496-501, 1984. 8. Andre, F.E., and
Safary, A.: Clinical experience with a yeast-derived hepatitis B vaccine. In
Zuckerman, A.J. (ed): Viral Hepatitis And Liver Disease, Alan R. Liss, Inc.,
1988, pp. 1025-1030. 9. Poovorawan, Y., et al.: Protective efficacy of a
recombinant DNA hepatitis B vaccine in neonates of HBe antigen-positive mothers.
JAMA. 261(22):3278-3281, June 9, 1989. 10. Goilav, C., et al.: Immunization of
homosexual men with a recombinant DNA vaccine against hepatitis B:
immunogenicity and protection. In Zuckerman, A.J. (ed): Viral Hepatitis And
Liver Disease, Alan R. Liss, Inc., 1988, pp. 1057- 1058. 11. Hauser, P., et al.:
Immunological properties of recombinant HBsAg produced in yeast. Postgrad. Med.
J. 63(Suppl. 2):83-91, 1987. 12. Centers for Disease Control: Recommendations of
the Immunization Practices Advisory Committee (ACIP): General Recommendations on
Immunization. MMWR. 38(13):April 7, 1989. 13. Centers for Disease Control and
Prevention: General Recommendations on Immunization: Recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR. 1994; 43(RR-1):6.
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