Prevention of hepatitis C virus infection in a chimpanzee by vaccination and epitope mapping of antiserum directed against hypervariable region 1

We previously reported on a chimpanzee immunized with both putative envelop e glycoproteins (E1 and E2) of hepatitis C virus (HCV), strain HCV-N2, and synthetic peptides of hypervariable region 1 (HVR1) of a different isolate, HCV-#6. The chimpanzee suggesting that an immune response to the HVR1 is m ore essential in protecting protection against HCV-#6 infection only when t he titer of anti-HVR1 increased, chimpanzee from HCV infection than an immu ne response to E1 and E2. In this study, immunized this chimpanzee with onl y synthetic HVR1 peptides after anti-E1 and antibody levels dropped and the n rechallenged with 10 infectious chimpanzee doses ai The immunized animal was protected, and neutralization of HCV with the antiserum the protected a nimal was achieved by inoculating another chimpanzee with HCV preneutralize d by this antiserum mixture. Epitope analysis of HVR1 by Pin-ELISA using an tiserum seemed to demonstrate that the antibody response was directed mainl y against the C terminus of HVR1. Moreover, our results showed that, if a p art of the sequences was conserved, a broad cross-reactivity of the antiser um could be observed, even if amino-acid sequences in this epitope were sub stituted for those of other HCV strains. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.