Objective: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response. Design: Single centre, randomised, double blind, dose-response study. Setting: Research vaccine evaluation centre at a teaching hospital. Subjects: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component. Intervention: Each subject was randomly allocated two doses of 5, 10, 20, or 40 mu g of a new hepatitis B vaccine two months apart Main outcome measures: Immunogenicity of the four doses. Seroconversion and seroprotection were defined as an antibody titre > 10 IU/l and > 100 IU/l respectively against an international antibody standard. Results: 69 subjects seroconverted after a single dose of the vaccine. After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects given 5 mu g of vaccine, 19 given 10 mu g, 16 given 20 mu g, and 20 given 40 mu g seroconverted. Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. Conclusion: A single dose of 20 mu g of the vaccine was as effective as two doses of either 40 mu g or 20 mu g of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.
