Immune response to hepatitis B vaccine with high antigen content in non-responders after standard primary vaccination in Chinese adults.

Context Alternative schedules are needed to provide greater immunogenicity in adults who fail to respond to the standard hepatitis B (HB) vaccine regimen. Objective To evaluate the immunogenicity and safety of high antigen content HB vaccine formulations administered to non-responders after routine primary vaccination. Design setting, and participants This was a phase III, double-blind, controlled clinical trial in China. We enrolled healthy participants (16–60 years old) seronegative for HB surface (HBs) antigen after primary vaccination, who had HBs antibody (anti-HBs) titres <10 mIU/ml at 28 days following routine vaccination with licensed HB vaccine containing 10 μg of antigen. Participants were randomised (2:2:1) to receive three booster doses of HB vaccine formulations containing 60 μg, 30 μg or 10 μg of antigen per dose 28 days apart. Blood samples were obtained pre-vaccination and 28 days after each dose to assess immunogenicity. Reactogenicity and safety were evaluated up to 28 days after each vaccine dose. Results Seroconversion rates were ≥92.1% and ≥87.1% as from the second dose of the 60 μg and 30 μg HB vaccine formulations, respectively, with geometric mean concentrations (GMCs) of ≥286.0 mIU/ml and ≥164.0 mIU/ml. In the 10 μg HB vaccine group the seroconversion rates were ≥83.0% and the GMCs ≥110.1 mIU/ml as from the second vaccine dose. All HB vaccine formulations were well tolerated: 352/1091 (32.3%) participants reported at least one injection-site or systemic adverse reaction (145/434 [33.4%] from the 60 μg group; 138/435 [31.7%] from the 30 μg group and 69/222 [31.1%] from the 10 μg group). Most reactions were mild or moderate and resolved within 24 h. No serious adverse events were reported. Conclusion Booster vaccination with a three-dose schedule of a high antigen content HB vaccine formulation was immunogenic and well tolerated in healthy adults. Clinicaltrials.gov identifier NCT01203319.