The Chimpanzee Model: Contributions and Considerations for Studies of Hepatitis B Virus

Efforts to control the global pandemic of human hepatitis B virus (hHBV) infection have been hampered by incomplete understanding of viral-host interactions in this disease. This situation has been confounded by the fact that hHBV has a limited host range and cannot be propagated in simple cell culture (1 ). Reproducible experimental infection with determination of infectivity was demonstrated in chimpanzees (Pan troglodytes ), but not other primates (2 –4 ), long before other animal models such as the woodchuck were identified. After successful inoculation of chimpanzees was reported in 1972, multiple institutions, including a multigroup collaboration between the FDA, CDC, and NIH, initiated studies to evaluate them as a model for the study of HBV. For the majority of studies only chimpanzees “with no prior exposure” to virus were used because those with positive serology [either from exposure to hHBV or chimpanzee HBV (chHBV)], with an estimated prevalence of 3–6% in Africa (5 ), were not reproducibly susceptible to infection (3 ). It has been widely reported that the effects of HBV infection in chimpanzees are milder than in humans, that is, few have developed fulminant hepatitis, and inoculated chimpanzees exhibit few symptoms or signs of infection. Furthermore, the incidence of chronic infection with HBV (see Table 2 ) and horizontal and vertical transmission (from mother to offspring) in chimpanzees is lower than in humans (6 ,7 ). Chimpanzees have been the cornerstone of all research on infectivity of HBV and safety and efficacy of vaccines.