Murine antibodies against E2 and hypervariable region 1 cross-reactively capture hepatitis C virus

The absence of readily available animal and cell culture models for hepatitis C virus (HCV) replication has bottlenecked research on protective immunity to HCV infection. Antibodies reactive with HCV virions in vitro are assumed to be candidates for neutralizing or inhibitory antibodies against HCV. To find potentially neutralizing or inhibitory antibody candidates, anti-C, anti-E1, anti-E2, and anti-HVR1 antisera acquired from mice immunized with corresponding recombinant proteins or synthetic peptides were used to capture HCV viral particles in vitro based on antibody-virus interaction assays. Both anti-E2 and anti-HVR1 antibodies effectively captured HCV in vitro. Furthermore, it was found that anti-E2 and anti-HVR1 antibodies could immunoprecipitate an isolate of HCV unrelated to the original antigenic HCV isolate. ELISA confirmed that anti-HVR1 antibodies cross-reactively bind to these unrelated HVR1 peptides. These findings suggest that anti-E2 and anti-HVR1 antibodies induced in mice have the ability to bind with HCV particles in an isolate cross-reactive manner and highlight the possible application of combining several sequences of HVR1 to generate broadly reactive anti-HVR1 antibodies.