Long-term prospective randomised study of hepatitis B vaccines without booster dose in children

Abstract

Introduction: Protective antibodies persisted up to 10 to 15 years after primary hepatitis B virus (HBV) vaccination. Titres of antibody against HBV surface antigen (anti-HBs) decrease with time. Necessity for routine booster dose remains controversial. Immunogenicity and efficacy of HBV vaccination without booster dose was examined in the present study. Methods: From 1984 to 1986, 318 Chinese children from HBV families aged 3 months to 11 years old were randomised into one of the three HBV vaccine regimens without booster doses—group A: 2-dose recombinant; group B: 3-dose recombinant; group C: 3-dose plasma-derived vaccines. HBV surface antigen (HBsAg) titres, anti-HBs, and antibody against HBV core antigen (anti-HBc), were measured yearly. Results: After 22 years, no subject was found to be HBsAg positive. Geometric mean titre (GMT) of antiHBs of group A subjects was significantly lower than that of group B and C subjects at year 1, 5, 10, and 15. No difference was observed in the GMTs between group B and C throughout the 22 years. At year 22, the proportion of subjects with anti-HBs ≥10 mIU/mL (the protective level) for groups A, B and C were 35.3%, 76.5%, and 52.4% respectively. The difference was statistically significant between groups A and B. A total of 72 subjects had ≥1 episodes of anamnestic response with rises in anti-HBs titres after the primary vaccination during the 22 years study period. Of these, eight anamnestic responses were mounted from subjects with the preceding antiHBs titre <10 mIU/mL. Three subjects became positive for anti-HBc. Conclusion: Protective anti-HBs persisted up to 22 years after HBV vaccination without the use of booster dose. The 3-dose regimens have a better long-term immunogenicity. However, the 2-dose recombinant HBV vaccine was not inferior to 3-dose vaccines in terms of protection against chronic HBV infection. Booster doses were not necessary, due to long-term immune memory.