Protective efficacy of a novel hepatitis B vaccine consisting of M (pre-S2 + S) protein particles (a third generation vaccine).

The protective efficacy of a new type of yeast-derived hepatitis B (HB) vaccine (TGP-943, subtype adr), which was formulated from modified M (pre-S2 + S; P31) protein (M-P31c) particles, was investigated in chimpanzees. Animals were injected intramuscularly three times at 4-week intervals with doses of 10 or 40 micrograms (as a protein) of TGP-943. There were no significant differences in the immunogenicity of 10 micrograms compared to that of 40 micrograms of TGP-943 in terms of anti-S antibody response, while the induction and persistence of anti-pre-S2 antibodies seemed dose-related. Chimpanzees, vaccinated with 40 micrograms of TGP-943, produced anti-pre-S2 antibodies 2 weeks after the first injection, which appeared earlier than anti-HBs (S) antibodies. A maximum level of the anti-pre-S2 antibodies was reached 2 weeks after the second injection. Apart from immunization with TGP-943, chimpanzees injected with denatured TGP-943, consisting of 10 micrograms (as a protein) of non-particulate M-P31c antigen, produced anti-pre-S2 antibodies with a non-protecting level of anti-S antibodies (less than 10 mIU ml-1). Five weeks after the third injection, all animals were challenged intravenously with 1000 chimpanzee infectious units of HBV subtype (ayw) and were protected as confirmed by normal serological markers, no signs of infection in the sera and liver biopsies, and no detection of HBV-DNA by PCR method. No side effects from inoculation with TGP-943 or denatured TGP-943 were also encountered in any animals.