ENHANCEMENT OF CELLULAR AND HUMORAL IMMUNE-RESPONSES TO HEPATITIS-C VIRUS CORE PROTEIN USING DNA-BASED VACCINES AUGMENTED WITH CYTOKINE-EXPRESSING PLASMIDS

Development of a broad based cellular and humoral immune response to h epatitis C virus (HCV) structural proteins may be important for irradi cation of infection. DNA-based immunization is a promising approach to generate HCV-specific immune responses. Previous studies of DNA-based immunizations in mice using an HCV core DNA expression plasmid (pHCV2 -2) demonstrated an efficient CTL response against HCV core epitopes; however, the humoral and Th cell proliferative responses were found to be weak. To enhance the immunogenicity of this nonsecreted viral stru ctural protein at the B and T cell level, we coimmunized mice with pHC V2-2 and DNA expression constructs encoding for mouse IL-2, IL-4, and granulocyte-macrophage CSF proteins. Under these experimental conditio ns, a seroconversion frequency to anti-HCV core increased from 40 to 8 0% in immunized mice. The CD4(+) inflammatory T cell proliferative res ponses as well as CD8(+) CTL activity to HCV core protein were enhance d substantially after coimmunization with the IL-2 and granulocyte-mac rophage CSF DNA expression constructs. In contrast, coimmunization wit h an IL-4-producing construct induced differentiation of Th cells towa rd a Th0 subtype and suppressed HCV core-specific CTL activity. Taken together, these studies emphasize that generation of antiviral immune responses using DNA-based immunization may be modified by local cytoki ne production at the site of Ag presentation.