Worldwide, 170 million people are chronically infected with Hepatitis C virus (HCV). Development of a safe and efficacious recombinant subunit vaccine for HCV is our long-term goal. Since the quality of the humoral response to viral envelop proteins and the breadth of the cellular response to multiple HCV proteins influence disease resolution, an HCV vaccine must be comprised of multiple HCV proteins and utilize a strategy which elicits broad based immunity. Feasibility of this approach was demonstrated in Phase I research within the production of five viral structural proteins. These proteins appear to have native-like structure, and each has specific attributes which make them attractive as subunit vaccine candidates. In Phase II research additional HCV proteins will be produced. Mice will be immunized with individual and combinations of proteins, and the composition of the humoral response and the extent and type of cellular response elicited will be evaluated. By dissecting the immune response, a vaccine strategy can be defined which maximizes each subunit's potential. In the last year of Phase II research, the identified vaccine strategy will be tested in primates. The information generated from Phase II research represents a crucial step in developing a multi-component vaccine against HCV. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE