Preliminary Study Of HCV NS3 Vaccine In Mice And Experimental Treatment Of Rabbit Cirrhosis Model

Chronic viral hepatitis and cirrhosis are major hepatic insults endanger health. Since the development of HBV vaccine, HCV infection has emerged as the most important causative agent of chronic hepatitis. Prevention of HCV infection and cure of cirrhosis have become the two most important tasks confronted by hepatologist. Current study presented preliminary results for these issues. Part I: Induction of Potent Cellular Immunity in Mice by HCV NS3 Protein Immunization with Double-Stranded RNABackground: Double-stranded RNA is produced during virus replication and is responsible for inducing host anti-virus immunity through Toll-like receptor 3 pathway. The HCV NS3 protein has been implicated in the immune evasion of HCV, and is one of the prime targets for raising immunity against HCV infection. Methods: Mice were immunized with recombinant NS3 protein (rNS3) and poly (I:C) emulsified in Montanide ISA 720 (M720). Cytokine production was assayed by ELISPOT, and CD4~+ IFN-γ~+ T helper cells or CD8~+ IFN-γ~+ cytotoxic lymphocytes (CTL) were detected by flow cytometry. Anti-NS3 titer and IgG2a, IgG1 amount was monitored by ELISA. Results: The cytokine profile showed that rNS3 formulated in poly (I:C) and M720 induced Thl-biased immunity with several fold more IFN-γ producing cells than IL-4 producing cells. In contrast, rNS3 in M720 without poly (I:C) induced Th2-biased immunity. The frequency of IFN-γ producing cells induced by rNS3 in poly (I:C) and M720 was significantly higher than that induced by rNS3 alone, rNS3 in M720, or rNS3 in poly (I:C), and was comparable to that induced by rNS3 in CpG oligo and M720. In addition, the percentage of CD8~+ IFN-γ~+ T cells induced by rNS3 formulated in poly (I:C) and M720 was comparable to that mduced by rNS3 in CpG oligo and M720. This CD8~+ T cell immune response persisted up to 7 months after immunization. Conclusion: Poly (I:C) with rNS3 in M720 can elicit strong and persistent specific CTL response and Th1-biased immunity in mice through cross-priming. It highlighted a promising formulation for inducing efficient cellular immunity against HCV and the potential for developing a clinical grade HCV vaccine.