Induction of Cell-Mediated Immune Responses in Mice by DNA Vaccines That Express Hepatitis C Virus NS3 Mutants Lacking Serine Protease and NTPase/RNA Helicase Activities

摘要: Effective therapeutic vaccines against virus infection must induce sufficient levels of cell-mediated immune responses the target viral epitopes and also avoid concomitant risk factors, such as potential carcinogenic properties. The nonstructural protein 3 (NS3) hepatitis C (HCV) carries a variety CD4+ CD8+ T cell epitopes, induces strong HCV-specific responses, which are correlated with clearance resolution acute HCV infection. On other hand, NS3 possesses serine protease nucleoside triphosphatase (NTPase)/RNA helicase activities, not only play important roles in life cycle but concomitantly interfere host defense mechanisms by deregulating normal cellular functions. In this study, we constructed series DNA that express HCV. To harm NS3, introduced mutations to catalytic triad (H57A, D81A S139A) NTPase/RNA domain (K210N, F444A, R461Q W501A) eliminate enzymatic activities. Immunization BALB/c mice each vaccine candidates (pNS3[S139A/K210N], pNS3[S139A/F444A], pNS3[S139A/R461Q] pNS3[S139A/W501A]) expresses an mutant lacking both NTPase/helicase activities induced degree comparable wild type NS3/4A complex, demonstrated interferon-γ production cytotoxic lymphocytes NS3. present study has plasmids expressing mutants, NS3(S139A/K210N), NS3(S139A/F444A), NS3(S139A/R461Q) NS3(S139A/W501A), lack would be good for safe efficient