Immunization of chimpanzees with hepatitis B virus-derived polypeptides

Abstract

Previous studies established that the purified polypeptides derived from the 22-nm particles associated with hepatitis B surface antigen (HBsAg) produce both humoral and cellular immunity against HBsAg in guinea pigs. Therefore, the two major polypeptides with molecular weights of 22,000 and 25,000 (P22 and P25, respectively) were isolated, adsorbed to an alum adjuvant, and used to immunize four nonimmune chimpanzees. A vigorous anti-HBs response was observed in all four animals after one inoculation of an alum-adsorbed polypeptide vaccine containing 40 micrograms of protein. After one to two booster inoculations, anti-HBs switched from being predominantly immunoglobulin M to the immunoglobin G class, indicating the establishment of immunological memory. Challenge of the vaccinated chimpanzees with 30,000 chimpanzee infectious doses of hepatitis B virus provided evidence for the efficacy of this vaccine. None of the four animals developed serological markers associated with an active hepatitis B infection, and no biochemical or histopathological changes of hepatitis were observed. A nonvaccinated control chimpanzee that was inoculated with the same hepatitis B virus material developed hepatitis B infection, confirming infectivity of the challenge inoculum.