Evaluation of new approaches to prophylactic and therapeutic vaccinations against hepatitis B viruses in the woodchuck model.

The woodchuck model is most suitable for vaccine studies of prophylaxis and therapeutic treatment of hepatitis B virus infection. Recently, methodological advances allowed the examination of antigen-specific T cell responses in woodchucks during woodchuck hepatitis virus (WHV) infection and vaccinations. Similar to hepatitis B virus infection in humans, multispecific T-cell responses to WHV occur during acute self-limiting infection in woodchucks. Immunizations with WHV core antigen (WHcAg) or DNA vaccines expressing WHcAg demonstrated that priming of specific T-cell responses leads to the control of WHV infection. B-cell responses but no T-cell responses to WHV surface antigens (WHsAg) were induced in chronically WHV-infected woodchucks by the therapeutic immunizations with WHsAg. Breaking T-cell tolerance appears to be critical for immunotherapeutic approaches to chronic hepatitis B.