Development and chimpanzee testing of a vaccine against human hepatitis B.

Highly purified hepatitis B virus surface antigen (Australia antigen) purified by physical and chemical procedures from infected human plasma was used to prepare hepatitis B vaccine. The purified antigen was treated with formalin and the vaccine was tested exhaustively for safety by ordinary procedures and additionally in marmosets (for live hepatitis B virus). The vaccine was highly potent, inducing antibody in guinea pigs, grivet monkeys, and chimpanzees given three doses of vaccine containing up to 20 mug of hepatitis B antigen per dose. A protective efficacy trial was carried out in chimpanzees that were given three doses of vaccine subcutaneously and then challenged intravenously with 1000 chimpanzee infectious doses of human hepatitis B virus. All of five unvaccinated control animals developed hepatitis B virus antigenemia following challenge and all of six vaccinated animals were protected, including one animal that had failed to develop detectable antibody following vaccination.