Project Summary Given the ongoing hepatitis C virus (HCV) pandemic, HCV vaccine development is an urgent priority. Despite the extraordinary genetic diversity of the virus, some antibodies are broadly neutralizing, meaning that these antibodies are able to block infection by genetically diverse HCV isolates. Stimulation of broadly neutralizing antibodies is likely to be a major component of a protective HCV vaccine, so accurate and standardized measurement of antibody titers and neutralization breadth is key to accelerating HCV vaccine development. However, there is currently no standard assay or panel of HCV envelope proteins or viruses used to measure antibody titers or neutralization. We propose here to develop pure HCV antigens and a standardized immunoassay for quantification of anti-HCV antibody responses to vaccination, and to develop a standardized HCV neutralization panel with genetically and phenotypically diverse viruses for quantification of neutralizing antibody responses to vaccination. These reference panels could be adopted as a standard for measurement of antibody titers and neutralizing breadth, which would allow meaningful comparisons of results obtained in different laboratories, and more rapid advancement of HCV vaccine development. Development of an HCV vaccine is an urgent priority. Accurate and standardized measurement of the titers, neutralizing potency and breadth of antibodies using diverse HCV isolates is key to evaluating HCV vaccine candidates and comparing results obtained in different laboratories. By generation of pure HCV antigens, a standardized immunoassay, and a standardized neutralization panel, we will facilitate accurate, reproducible measurements of antibody responses, and accelerate HCV vaccine development.