Immunogenicity of a 'pre-S2 plus S' hepatitis B vaccine in healthy adults.

The product of the pre-S plus S gene of hepatitis B virus appears to be more immunogenic in mice than the S-gene product (HBsAg) alone. Therefore, we tested the immunogenicity in healthy adults of a hepatitis B vaccine containing the 'middle protein' gene product of pre-S2 plus S (pre-S vaccine). We compared the immunogenicity of three doses of the pre-S vaccine with that of a commercially available recombinant hepatitis B vaccine (Recombivax-HB); 87 seronegative adults were randomized to receive 12 micrograms (group 1), 24 micrograms (group 2), or 48 micrograms (group 3) of the pre-S vaccine or 10 micrograms of Recombivax-HB (group 4) by deltoid injection at 0, 1 and 6 months. Antibody to HBsAg (anti-HBs) appeared after booster vaccination in > or = 94% of vaccinees. Immunogenicity was best in recipients of 48 micrograms of the pre-S vaccine and Recombivax-HB, and geometric mean titres (GMT) for the pre-S vaccine were higher than those for Recombivax-HB only at the pre-S vaccine dose of 48 micrograms (group 3). Antibody to pre-S2 developed in 75% of the pre-S2 vaccine recipients (not in Recombivax-HB recipients) within 7 months. These findings indicate that the pre-S vaccine is immunogenic in healthy adults but that a dose of 48 micrograms of the current formulation is required to equal or exceed the immunogenicity of currently available, recombinant S-only vaccine. Studies in non-responders to S-only vaccines will be necessary to define an immunological advantage of the pre-S vaccines, and additional assessments will be necessary to determine whether anti-pre-S2 enhances protective efficacy.