Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection

Hepatitis C virus (HCV) infections were evaluated in chimpanzees that had p reviously cleared HCV and were rechallenged. Animals that had previously cl eared HCV infection rapidly cleared homologous and heterologous virus upon rechallenge, indicative of a strong protective immunity. In one animal, ste rilizing immunity was observed with regard to viremia, although viral RNA w as transiently detected in the liver. Accelerated viral clearance following rechallenge with HCV was observed in animals that had not been exposed to HCV for over 16 years, suggesting that long-lasting protective immunity may be possible. The ability of peripheral blood mononuclear cells (PBMC) to r ecognize HCV proteins was evaluated during the course of the rechallenge ex periments. A very early and strong in vitro recall response to HCV nonstruc tural proteins appeared to be associated with viral clearance. in contrast, proliferative responses to HCV proteins were not observed in 4 persistentl y infected chimpanzees, and a weak proliferative response was observed in 1 of 2 animals during acute resolving infection. The results suggest that a strong T-cell proliferative response is induced upon rechallenge of chimpan zees with HCV and that this response is associated with rapid viral clearan ce. The antibody response to HCV proteins increased by over 1,000-fold in a ll animals following rechallenge as well. A more complete understanding of the role of the cellular immune response in the clearance of HCV and the na ture of the protective immune response following viral clearance may aid in the generation of therapies and vaccines.