Monoclonal antibodies to the hypervariable region 1 of hepatitis C virus capture virus and inhibit virus adsorption to susceptible cells in vitro

To analyze the neutralizing-related activity of antibodies against the hype rvariable region 1 (HVR1) of hepatitis C virus (HCV) in more detail, monocl onal antibodies (mAbs) against HVR1 were raised by immunizing various strai ns of mice with one of two synthetic HVR1 peptides that had been derived fr om two isolates of HCV. The epitope specificity of all six mAbs could be as signed by the use of a series of linear peptides in competitive ELISA. It s eems that most subregions In the amino acid sequence of HVR1 can induce a h umoral immune response in mice. All three mAbs specific to HVR1-6-1 had the ability to capture homologous HCV-6 and inhibit its absorption to suscepti ble cells in vitro despite the fact that the epitope of each mAb was at a d ifferent location in HVR1, whereas the other three mAbs specific to HVR1-7 could not capture HCV-B nor inhibit the absorption of HCV-6 to susceptible cells. The data in this study suggest that mAbs against HVR1 can prevent th e infectivity of HCV in an isolate-specific and epitope position-independen t manner. (C) 2000 Academic Press.