Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus

The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface prote in has raised the possibility that such variants represent neutralization e scape mutants, We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present stud y, the protective efficacy of licensed hepatitis B vaccines was evaluated a gainst challenge with this mutant virus, Four chimpanzees were immunized wi th 1 of 2 licensed recombinant hepatitis B vaccines. Shortly after the chim panzees developed antibodies to hepatitis B surface antigen (anti-HBs), the y were challenged intravenously with mutant HBV strain AS. Two unvaccinated chimpanzees served as positive controls. The 4 vaccinated chimpanzees did not develop evidence of HBV infection or hepatitis during 2 years following virus challenge. In contrast, the 2 unvaccinated chimpanzees developed HBV infection and hepatitis. Serum anti-HBs in the vaccinated chimpanzees reac ted not only with wild-type surface antigen, but also with mutant surface a ntigen by competition enzyme-linked immunosorbent assay (ELISA), Thus, immu nization of chimpanzees with licensed recombinant hepatitis B vaccines stim ulates anti-HBs that is broadly reactive and affords protection against inf ection with a surface gene mutant of HBV, suggesting that properly immunize d individuals are not at significant risk of infection with this prototype variant strain of HBV.