Development of T-cell vaccine for hepatitis C virus

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We tried to develop T-cell vaccine to prevent and treat hepatitis C virus (HCV) infection. We established cytotoxic T cell clones from peripheral blood lymphocytes of two HLA B44-positive patients with chronic HCV infection that recognize HCV core antigen 88-96 as a minimal and optimal epitope. We demonstrated that positions 4 and 6 of the 9 amino acid epitope were important for the binding of the epitope and T-cell antigen receptors of the CTL clones. When amino acids at positions 4 and 7 were substituted by other amino acids, a wild type epitope for type 1b and 2a HCV (NEGLGWAGW) and a variant type for 2b HCV (NEGCGWMGW) were recognized most efficitntly by CTL slones. HCV DNA that express HCV core antigen in the tranfected mammalian cells induced HCV-specific CTL when the DNA was injected directly into the spleen of mice. Intramuscular injection of the DNA did not induce CTL in either mice or chimpanzees.