Summary Chronic hepatitis C virus (HCV) infection affects an estimated 71 million people worldwide. Chronic HCV infection frequently leads to liver cirrhosis and predisposes infected individuals to liver cancer. Approximately, 400,000 die from HCV-related complications a year. While a cure for HCV has recently been developed, access to and affordability of this treatment is limited. Furthermore, less than 20% of chronically infected individuals are aware of their diagnosis. Therefore, to eliminate HCV, a vaccine is still urgently needed. Because of the genetic variability of the HCV, to date HCV vaccines that have been tested clinically have not been successful at preventing chronic infection. This study takes advantage of recent structural data of HCV antigen complexes, computational methods to optimize antigen structure presentation, multivalent presentation of those antigens on self-assembling nanoparticles, and preclinical testing in a nonhuman primate model that has demonstrated strong predictive value of human antibody responses. Core C: NHP, based at the Southwest National Primate Research Center, will evaluate the immunogenicity of rationally designed HCV vaccine antigens and nanoparticles using a non-human primate (NHP) model, rhesus macaques, and collect blood and tissue samples to enable in-depth analysis of the immune responses elicited by the vaccine antigens in this P01 research program.