Mechanism Of Action
Infection with hepatitis B virus can have serious consequences including acute massive hepatic necrosis
and chronic active hepatitis. Chronically infected persons are at increased
risk for cirrhosis and hepatocellular carcinoma.
Antibody concentrations ≥ 10 mIU/mL against HBsAg are recognized as conferring protection against hepatitis B virus
infection.1 Seroconversion is defined as antibody titers ≥ 1 mIU/mL.
Efficacy In Neonates
Protective efficacy with ENGERIX-B has been demonstrated in a clinical trial in neonates at high risk of
hepatitis B infection.6,7 Fifty-eight neonates born of mothers who
were both HBsAg- positive and hepatitis B “e” antigen (HBeAg)-positive were
given ENGERIX-B (10 mcg/0.5 mL) at 0, 1, and 2 months, without concomitant
hepatitis B immune globulin (HBIG). Two infants became chronic carriers in the
12-month follow-up period after initial inoculation. Assuming an expected
carrier rate of 70%, the protective efficacy rate against the chronic carrier
state during the first 12 months of life was 95%.
Efficacy And Immunogenicity In Specific Populations
ENGERIX-B (20 mcg/1 mL) given at 0, 1, and 6 months was evaluated in homosexual men 16 to 59 years of age.
Four of 244 subjects became infected with hepatitis B during the period prior
to completion of the 3-dose immunization schedule. No additional subjects
became infected during the 18-month follow-up period after completion of the
Adults with Chronic Hepatitis C
In a clinical trial of 67 adults 25 to 67 years of age with chronic hepatitis C, ENGERIX-B (20 mcg/1 mL)
was given at 0, 1, and 6 months. Of the subjects assessed at Month 7 (N = 31),
100% responded with seroprotective titers. The geometric mean antibody titer
(GMT) was 1,260 mIU/mL (95% Confidence Interval [CI]: 709, 2,237).
Adults on Hemodialysis
Hemodialysis patients given hepatitis B vaccines respond with lower titers, which remain at protective
levels for shorter durations than in normal subjects. In a clinical trial of 56
adults who had been on hemodialysis for a mean period of 56 months, ENGERIX-B
(40 mcg/2 mL given as two 1-mL doses) was given at 0, 1, 2, and 6 months. Two
months after the fourth dose, 67% (29/43) of patients had seroprotective
antibody levels ( > 10 mIU/mL) and the GMT among seroconverters was 93 mIU/mL.
Adults with Type 2 Diabetes Mellitus
In a descriptive study, 674 adult subjects with type 2 diabetes (diagnosed within the preceding 5 years) or
without type 2 diabetes were enrolled and stratified by age and body mass index
(BMI). The per-protocol immunogenicity cohort included 378 diabetic subjects
and 189 matched control subjects who received ENGERIX-B (20 mcg/1 mL) at 0, 1,
and 6 months. Among these subjects, the mean age was 54 years (range: 20 to 82
years); mean BMI was 32 kg/m (range: 17 to 64 kg/m ); 51% were male; 88% were
white, 3% were American Indian or Alaskan Native, 3% were black, 2% were Asian,
4% were other racial groups; 2% were Hispanic or Latino.
The overall seroprotection rates (1 month after the third dose) were 75% (95% CI: 71, 80) in patients with
diabetes and 82% (95% CI: 76, 87) in control subjects. The seroprotection rates
in those with diabetes aged 20 to 39 years, 40 to 49 years, 50 to 59 years, and
at least 60 years were 89%, 81%, 83%, and 58%, respectively. The seroprotection
rates in those without diabetes in these same age-groups were 100%, 86%, 82%
and 70%, respectively. Subjects with diabetes and a BMI of at least 30 kg/m had
a seroprotection rate of 72% compared with 80% in diabetic subjects with lower
BMIs. In control subjects, seroprotection rates were 82% in those with a BMI of
at least 30 kg/m² and 83% in those with lower BMIs.
Immunogenicity In Neonates
In clinical studies, neonates were given ENGERIX-B (10 mcg/0.5 mL) at 0, 1, and 6 months or at 0, 1, and 2
months of age. The immune response to vaccination was evaluated in sera
obtained 1 month after the third dose of ENGERIX-B.
Among infants administered ENGERIX-B at 0, 1, and 6 months, 100% of evaluable subjects (N = 52)
seroconverted by Month 7. The GMT was 713 mIU/mL. Of these, 97% had
seroprotective levels ( ≥ 10 mIU/mL).
Among infants enrolled (N = 381) to receive ENGERIX-B at 0, 1, and 2 months of age, 96% had seroprotective
levels ( ≥ 10 mIU/mL) by Month 4. The GMT among seroconverters (N = 311) (antibody titer ≥ 1 mIU/mL) was 210
mIU/mL. A subset of these children received a fourth dose of ENGERIX-B at 12
months of age. One month following this dose, seroconverters (N = 126) had a
GMT of 2,941 mIU/mL.
Immunogenicity In Children And Adults
Persons 6 Months through 10 Years of Age
In clinical trials, children (N = 242) 6 months through 10 years of age were given ENGERIX-B (10 mcg/0.5 mL) at
0, 1, and 6 months. One to 2 months after the third dose, the seroprotection
rate was 98% and the GMT of seroconverters was 4,023 mIU/mL.
Persons 5 through 16 Years of Age
In a separate clinical trial including both children and adolescents 5 through 16 years of age, ENGERIX-B
(10 mcg/0.5 mL) was administered at 0, 1, and 6 months (N = 181) or 0, 12, and
24 months (N = 161). Immediately before the third dose of vaccine,
seroprotection was achieved in 92.3% of subjects vaccinated on the 0-, 1-, and
6-month schedule and 88.8% of subjects on the 0-, 12-, and 24-month schedule
(GMT: 117.9 mIU/mL versus 162.1 mIU/mL, respectively, P = 0.18). One month
following the third dose, seroprotection was achieved in 99.5% of children
vaccinated on the 0-, 1-, and 6-month schedule compared with 98.1% of those on
the 0-, 12-, and 24-month schedule. GMTs were higher (P = 0.02) for children
receiving vaccine on the 0-, 1-, and 6-month schedule compared with those on
the 0-, 12-, and 24-month schedule (5,687.4 mIU/mL versus 3,158.7 mIU/mL, respectively).
Persons 11 through 19 Years of Age
In clinical trials with healthy adolescent subjects 11 through 19 years of age, ENGERIX-B (10 mcg/0.5 mL) given
at 0, 1, and 6 months produced a seroprotection rate of 97% at Month 8 (N = 119)
with a GMT of 1,989 mIU/mL (N = 118, 95% CI: 1,318, 3,020). Immunization with
ENGERIX-B (20 mcg/1 mL) at 0, 1, and 6 months produced a seroprotection rate of
99% at Month 8 (N = 122) with a GMT of 7,672 mIU/mL (N = 122, 95% CI: 5,248,
Persons 16 through 65 Years of Age
Clinical trials in healthy adult and adolescent subjects (16 through 65 years of age) have shown that
following a course of 3 doses of ENGERIX-B (20 mcg/1 mL) given at 0, 1, and 6
months, the seroprotection (antibody titers > 10 mIU/mL) rate for all
individuals was 79% at Month 6 (5 months after second dose) and 96% at Month 7
(1 month after third dose); the GMT for seroconverters was 2,204 mIU/mL at
Month 7 (N = 110).
An alternate 3-dose schedule (20 mcg/1 mL given at 0, 1, and 2 months) designed for certain populations
(e.g., individuals who have or might have been recently exposed to the virus
and travelers to high-risk areas) was also evaluated. At Month 3 (1 month after
third dose), 99% of all individuals were seroprotected and remained protected
through Month 12. On the alternate schedule, a fourth dose of ENGERIX-B (20
mcg/1 mL) at 12 months produced a GMT of 9,163 mIU/mL at Month 13 (1 month
after fourth dose) (N = 373).
Persons 40 Years of Age and Older
Among subjects 40 years of age and older given ENGERIX-B (20 mcg/1 mL) at 0, 1, and 6 months, the
seroprotection rate 1 month after the third dose was 88% and the GMT for
seroconverters was 610 mIU/mL (N = 50). In adults older than 40 years of age,
ENGERIX-B produced anti-HBsAg antibody titers that were lower than those in
Interchangeability With Other Hepatitis B Vaccines
A controlled study (N = 48) demonstrated that completion of a course of immunization with 1 dose of
ENGERIX-B (20 mcg/1 mL) at Month 6 following 2 doses of RECOMBIVAX HB® (10 mcg) at Months 0 and 1 produced a similar GMT (4,077
mIU/mL) to immunization with 3 doses of RECOMBIVAX HB (10 mcg) at Months 0, 1,
and 6 (GMT: 2,654 mIU/mL). Thus, ENGERIX-B can be used to complete a
vaccination course initiated with RECOMBIVAX HB.8
5. Centers for Disease Control
and Prevention. A Comprehensive Immunization Strategy to Eliminate Transmission
of Hepatitis B Virus Infection in the United States. Recommendations of the
Advisory Committee on Immunization Practices (ACIP). Part 2: Immunization of
Adults, MMWR 2006;55(RR-16);1-25.
6. Andre FE, Safary A. Clinical
experience with a yeast-derived hepatitis B vaccine. In: Zuckerman AJ, ed. Viral
Hepatitis and Liver Disease. New York, NY: Alan R Liss, Inc.; 1988:1025-1030.
7. Poovorawan Y, Sanpavat S,
Pongpunlert W, et al. Protective efficacy of a recombinant DNA hepatitis B
vaccine in neonates of HBe antigen-positive mothers. JAMA. 1989;261(22):3278-
8. Bush LM, Moonsammy GI,
Boscia JA. Evaluation of initiating a hepatitis B vaccination schedule with one
vaccine and completing it with another. Vaccine. 1991;9(11):807-809.