"Can Broadly Neutralizing Antibodies Lead Us to an HCV Vaccine?"
Abstract: Hepatitis C virus (HCV) infects over 71 million people worldwide and kills more people in the United States annually than HIV. Direct-acting antiviral (DAA) therapy has revolutionized care, but development of a vaccine for HCV remains essential for disease eradication. The enormous genetic diversity of HCV makes this a daunting challenge. Early development of broadly-neutralizing antibodies is associated with spontaneous clearance of HCV infection, but the mechanisms of immune-mediated clearance are poorly defined. We have isolated broadly neutralizing monoclonal antibodies (bNAbs) from individuals who cleared HCV infection, and studied how these antibodies can drive viral evolution, leading to a loss of replicative fitness. We are also studying the structural interactions between these bNAbs and HCV envelope proteins to identify conserved binding epitopes and antibody features critical for neutralizing breadth, with the goal of informing HCV vaccine development.