CELLULAR AND HUMORAL IMMUNE-RESPONSE TO HEPATITIS-B VIRUS STRUCTURAL PROTEINS IN MICE AFTER DNA-BASED IMMUNIZATION

Background & Aims: Development of a broad-based cellular immune respon se to hepatitis B viral structural proteins may be important for recov ery from infection, and lack of such responses may lead to persistent viral infection and chronic liver disease. Strategies designed to enha nce the hepatitis B virus (HBV)-specific immune response may be able t o reduce persistent viral infection of the liver, The aim of this stud y was to induce HBV-specific cellular and humoral immune responses in mice using DNA-based immunizations with the large and middle envelope and nucleocapsid proteins, Methods: Antibodies to HBV structural prote ins, T-helper-cell proliferation, and cytokine release and generation of cytotoxic T lymphocyte (CTL) activity were measured in vaccinated m ice, Results: Immunized mice developed high-titer antibodies against e nvelope and core proteins in serum. More importantly, 93% of the immun ized mice produced strong inflammatory CD4(+) T-cell and CD8(+) CTL re sponses to viral proteins, Conclusions: This study shows that DNA-base d vaccination will generate broad-based CTL activity as well as strong T-helper cell responses with the production of TH1-type cytokines to HBV structural proteins. Such constructs are promising candidates as a ntiviral agents, and these studies have defined some of the most immun ogenic antigens for an immunotherapeutic approach of chronic HBV infec tion.