Prevention and treatment of HCV infection employing antibodies that inhibit the interaction of HCV virions with their receptor

摘要

Human monoclonal antibodies binding to epitopes common to type 1 and 2 HCV are provided, as well as conformationally conserved HCV E2 2a and 2b proteins. Compositions comprising the antibodies find use in diagnosis and therapy. The antibodies recognize conformational epitopes that are conserved across multiple genotypes of HCV. Thus the antibodies have the potential to be useful in the prevention and treatment of the majority of HCV infections. A subset of the antibodies (CBH-2, CBH-5, CBH-7, CBH-8C, CBH-8E, and CBH-11) have the ability to prevent the binding of HCV E2 proteins of multiple genotypes to human CD81, a possible co-receptor for HCV infection. A subset of the antibodies (CBH-2 and CBH-5) have been shown to inhibit the binding of HCV virions (as opposed to purified E2 protein) to human CD81. A further subset of the antibodies (CBH-4D, CBH4B, CBH-8C, and CBH-9) have been shown to prevent HCV envelope mediated fusion using an HCV psuedotype system.