Antibody Levels and Protection After Hepatitis B Vaccination: Results of a 15-year Follow-up

Background: The duration of protection afforded by hepatitis B vaccination is unknown.

Objective: To determine antibody persistence and protection from hepatitis B virus (HBV) infection.

Design: Prospective cohort study.

Setting: 15 villages in southwest Alaska.

Participants: 1578 Alaska Natives vaccinated at age 6 months or older.

Intervention: During 1981-1982, participants received 3 doses of plasma-derived hepatitis B vaccine. This cohort was followed annually over the first 11 years, and 841 (53%) persons were tested at 15 years.

Measurements: Antibody to hepatitis B surface antigen (anti-HBs), markers of HBV infection, and testing to identify HBV variants.

Results: Levels of anti-HBs in the cohort decreased from a geometric mean concentration of 822 mIU/mL after vaccination to 27 mIU/mL at 15 years. Initial anti-HBs level, older age at vaccination, and male sex were associated with persistence of higher anti-HBs levels at 15 years when analyzed by a longitudinal linear mixed model. After adjustment for initial anti-HBs level and sex, those vaccinated at age 6 months to 4 years had the lowest anti-HBs level at 15 years. Asymptomatic breakthrough infections were detected in 16 participants and occurred more frequently in persons who did not respond to vaccination than those who responded (P = 0.01). Among infected persons with viremia, 2 were infected with wild-type HBV and 4 had HBV surface glycoprotein variants, generally accompanied by wild-type HBV.

Limitations: The loss of participants to follow-up at 15 years was 47%. However, characteristics of persons tested were similar to those of persons lost to follow-up.

Conclusions: Hepatitis B vaccination strongly protected against infection for at least 15 years in all age groups. Antibody levels decreased the most among persons immunized at 4 years of age or younger.