Broadly Effective HCV Vaccine

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Program Summary The overarching goal of this P01 proposal is to develop novel hepatitis C virus (HCV) vaccine candidates that can elicit potent broadly neutralizing antibody responses in immunization. Despite highly effective antiviral drugs against HCV now being available, the continuous increase in new infections underscores the real-world challenges in combating this human infection without a vaccine. This P01 proposal “Broadly Effective Hepatitis C Vaccine” is built on the hypothesis that an HCV vaccine effective against diverse circulating HCV strains can be developed through rational engineering of vaccines to enhance antigen immunogenicity and presentation of conserved neutralizing epitopes, and to target well-defined multidonor class broadly neutralizing antibody (bnAb) responses to HCV. Multidonor class antibody responses are antibodies sharing common genetic and functional features produced in infection or vaccination at the population level. This P01 program consists of 2 research projects, supported by an admin core and 2 scientific cores. The overall aims of the program are: (1) To determine the structures of HCV envelope glycoproteins important for rational vaccine design; (2) To rationally design HCV vaccine antigens for elicitation of broadly neutralizing antibodies that will be effective against diverse circulating viral strains; (3) To determine the antibody responses elicited by HCV vaccine antigens in preclinical animal models. Success in this research program will result in both basic scientific knowledge and a strong HCV vaccine candidate for future pilot production and clinical testing.