The overarching goal of this proposal is to isolate a large and representative set of E1E2-specific broadly neutralizing antibodies (bNAbs), bNAb unmutated ancestors, and bNAb intermediates from Elite Neutralizers (EN), individuals with broadly neutralizing plasma and spontaneous clearance of HCV infection. Together, these studies will identify a large, representative set of bNAbs associated with spontaneous clearance of HCV, defining key epitope residues and structural features in E1E2 that could be stabilized to optimize vaccine antigens. These studies will inform structure-based design efforts to improve E1E2-based vaccine candidates, which is an urgent challenge with global public health implications.