PREVENTION OF HEPATITIS-C VIRUS-INFECTION IN CHIMPANZEES AFTER ANTIBODY-MEDIATED IN-VITRO NEUTRALIZATION

Hepatitis C virus (HCV) is the most important etiologic agent of non-A , non-B hepatitis and is a major cause of chronic liver disease and he patocellular carcinoma, Development of an effective vaccine would be t he most practical method for prevention of the infection, but whether infection with HCV elicits protective immunity in the host is unclear. Neutralization of HCV in vitro was attempted with plasma of a chronic ally infected patient, and the residual infectivity was evaluated by i noculation of eight seronegative chimpanzees. The source of HCV was pl asma obtained from a patient during the acute phase of posttransfusion non-A, non-B hepatitis, which had previously been titered for infecti vity in chimpanzees. Neutralization was achieved with plasma obtained from the same patient 2 yr after the onset of primary infection but no t with plasma obtained 11 yr later, although both plasmas contained an tibodies against nonstructural and structural (including envelope) HCV proteins. Analysis of sequential viral isolates from the same patient revealed significant genetic divergence as early as 2 yr after infect ion. However, the HCV recovered from the patient 2 yr after the infect ion had a striking sequence similarity with the HCV recovered from one of the chimpanzees inoculated with the acute-phase virus, suggesting that the progenitor of the new strain was already present 2 yr earlier . This evidence, together with the different sequences of HCV recovere d from the chimpanzees that received the same inoculum, confirms that HCV is present in vivo as a quasispecies. These results provide experi mental evidence in vivo that HCV infection elicits a neutralizing anti body response in humans but suggest that such antibodies are isolate-s pecific. This result raises concerns for the development of a broadly reactive vaccine against HCV.