PREVENTION OF HEPATITIS-C VIRUS-INFECTION IN CHIMPANZEES BY HYPERIMMUNE SERUM AGAINST THE HYPERVARIABLE REGION-1 OF THE ENVELOPE-2 PROTEIN

The identification of the neutralization domains of hepatitis C virus (HCV) is essential for the development of an effective vaccine. sere, we show that the hypervariable region 1 (HVR1) of the envelope 2 (E2) protein is a critical neutralization domain of HCV. Neutralization of HCV in vitro was attempted with a rabbit hyperimmune serum raised agai nst a homologous synthetic peptide derived from the HVR1 of the E2 pro tein, and the residual infectivity was evaluated by inoculation of HCV -seronegative chimpanzees. The source of HCV was plasma obtained from a patient (H) during the acute phase of posttransfusion non-A, non-B h epatitis, which hall been titered for infectivity in chimpanzees. The anti-HVR1 antiserum induced protection against homologous HCV infectio n in chimpanzees, but not against the emergence of neutralization esca pe mutants that were found to be already present in the complex viral quasispecies of the inoculum. The finding that HVR1 can elicit protect ive immunity opens new perspectives for the development of effective p reventive strategies. However, the identification of the most variable region of HCV as a critical neutralization domain poses a major chall enge for the development of a broadly reactive vaccine against HCV.