Multiple sequence-reactive antibodies induced by a single peptide immunization with hypervariable region 1 of hepatitis C virus

Abstract

Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) is known to contain neutralizing epitopes. We previously found that murine antibodies against HVR1-6 captured a different isolate, HCV-7, and cross-reacted with the HVR1 peptide of HCV-7. We investigated the inducibility and generality of cross-reaction of animal anti-HVR1 antibody responses in this study. Anti- HVRI-7 antibodies, which were induced in mice and a chimpanzee by immunization, were found to be cross-reactive to HVR1-6 peptide. Antibody responses against HVR1-6-1 and HVR1-7 peptides were detected in 11/165 (6.7%) and 26/165 (15.8%) HCV-infected individuals, respectively. Nine HVR1 sequences from six individuals, who were strongly positive for anti-HVR1-7 antibodies, were only 50-64.5% identical to that of HVR1-7. All nine of these HVR1 peptides were reactive to sera from the six patients and/or to antisera against HVR1-6 and HVR1-7 produced in mice and chimpanzees. Cross-inhibition tests of chimpanzee antisera indicated that a given species of anti-HVR1 antibodies was reactive to multiple HVR1 sequences. Fine epitope mapping of polyclonal and monoclonal anti-HVR1 antibodies showed that conserved subregions in HVR1 sequences determined the observed immunological cross- reactivity. Our data demonstrate that cross-reacting anti-HVR1 antibodies are inducible by a single peptide immunization.