Project 1 Summary HCV infects nearly 3% of the world population and is a leading cause of liver cirrhosis and cancer. A vaccine that can stop virus transmission will be a highly valuable tool for the public health system. However, HCV is antigenically variable and an effective vaccine must target conserved immune epitopes on the virus. An important goal in HCV vaccine is to develop antigens that will elicit broadly neutralizing antibodies (bNAbs). The proposed project aims to discover the epitopes targeted by bNAbs during vaccination and natural infection, and the evolutionary pathways of bnAbs. The knowledge learned from the human studies will be applied to studying the antibody responses in mice, guinea pigs and non-human primates immunized with candidate HCV vaccine antigens. The research will help uncover the pros and cons of each animal model as a preclinical model for efficacy study of future HCV vaccine candidates. This project will contribute to the knowledge and tools for the development of a broadly effective HCV vaccine.