Some considerations regarding active immunization with HBsAg.

Krugman has demonstrated that injection of heated serum containing HBsAg conferred some protection against subsequent challenge with live hepatitis B virus (HBV). It is likely that improved protection will result from injections for larger quantities of HBsAg. This can be readily done with purified antigen. We have carried out preliminary studies in mice to investigate the inactivation kinetics of HBsAg antigenicity and immunogenicity. Rates of inactivation of the two parameters by heat have been found to be parallel. Chimpanzees will be required to determine adequacy of inactivation procedures, and optimal dose and immunization schedule, prior to the initiation of human trials. The use of newly imported chimpanzees for this purpose may be hazardous. Of 27 chimpanzees recently tested in an exporter's compound in Sierra Leone, ten were found to circulate HBsAg and five additional had detectable anti-HBs, suggesting a high risk of hepatitis B transmission within the compound. Thus newly imported animals may be incubating HB infection, and could give rise to false positive results in inactivation trials, unless quarantined for a four to six month period prior to use. We have therefore established a laboratory for chimpanzee trials in West Africa, and plan to utilize only animals captured by trapping and held in strict isolation from the time of capture. It is unlikely that immunization against HBV will ever provide absolute immunity. Three chimpanzees who received a massive transfusion of infective plasma one year after resisting challenge with aliquots of the same plasma inoculated intraperitoneally, all developed severe hepatitis, accompanied in two cases by HBs antigenemia, despite strong anamnestic anti-HBs responses in all three animals.