Human monoclonal antibody to hepatitis C virus El glycoprotein that blocks virus attachment and viral infectivity

Human antibodies elicited in response to hepatitis C virus (HCV) infection are anticipated to react with the native conformation of the viral envelope structure. Isolation of these antibodies as human monoclonal antibodies that block virus binding and entry will be useful in providing potential therapeutic reagents and for vaccine development. H-111, an antibody to HCV envelope 1 protein (E1) that maps to the YEVRNVSGVYH sequence and is located near the N terminus of El and is able to immunoprecipitate E1E2 heterodimers, is described. Binding of H-111 to HCV El genotypes la, 1b, 2b, and 3a indicates that the H-111 epitope is highly conserved. Sequence analysis of antibody V regions showed evidence of somatic and affinity maturation of H-111. Finally, H-111 blocks HCV-Iike particle binding to and HCV virion infection of target cells, suggesting the involvement of this epitope in virus binding and entry.