DIFFERENTIAL CELLULAR AND HUMORAL IMMUNE-RESPONSES TO HCV CORE AND HBV ENVELOPE PROTEINS AFTER GENETIC IMMUNIZATIONS USING CHIMERIC CONSTRUCTS

Development of a broad based cellular and humoral immune response to h epatitis C virus (HCV) structural proteins may be important for eradic ation of viral infection. In previous studies in mice we demonstrated that facilitated DNA-based immunization with an HCV core DNA-expressio n construct stimulated the generation of weak cytotoxic T lymphocyte ( CTL), helper T cell (Th), and humoral immune responses against HCV cor e related epitopes. To enhance the immunogenicity of the non-secreted viral structural protein at both the B- and T-cell level, several chim eric HBV-HCV constructs were prepared which were designed to express a nd secrete HCV core protein along with various regions of the hepatiti s B envelope protein. No secretion of the chimeric proteins into the c ulture supernatant was detected using sensitive radio-immunoassays, Ho wever such chimeric proteins were capable of generating CD4+ inflammat ory T cell and CD8+ CTL activity against both HBV and HCV components o f the fusion proteins. It was determined that the proliferative activi ty of T cells as well as the humoral immune responses to HCV core prot ein were substantially enhanced by some chimeric fusion proteins as co mpared to the HCV core protein alone. The strength of the immune respo nses appeared directly related to the level of Th1 cytokines produced by CD4+ T cells obtained from immunized animals, Further characterizat ion of the immune responses stimulated by these DNA constructs studied helped to define some of the most immunogenic regions of the chimeric proteins that they encode. (C) 1998 Elsevier Science Ltd. All rights reserved.