Chronic hepatitis B virus infection is a serious worldwide health problem for which there is no effective treatment for most patients. The goal of the present proposal is to develop an HBV-specific vaccine capable of eliciting HLA class I-restricted CTL that will eliminate hepatitis B virus from chronically-infected patients . During the SBIR Phase I study, the investigators: 1) identified an optimal HBV-specific CTL epitope and 2) modified the peptide cells expressing the appropriate HBV antigen. Based on this, a Phase I clinical trial was performed in which it was shown that an effective cytotoxic immune response could be generated in man to the chosen CTL epitope. The present application proposes to: 1) enhance the vaccine T helper function, 2) determine optimal procedures for immunization with multiple CTL epitopes, and 3) define which CTL epitopes can mount an immune response in animals that are immunologically tolerant to the whole virus. This technology represents a novel therapeutic approach with broad ranging potential application to many diseases other than hepatitis B infection, including hepatitis C, HIV, herpes viruses, tuberculosis, malaria and many forms of cancer