Therapeutic vaccination in chronic hepadnavirus infection

Interferon α and nucleoside analogues are available for treatment of chronic hepatitis B virus (HBV) infection but do not lead to a satisfactory result. New findings about the immunological control of HBV during acute infection suggest the pivotal role of T-cell mediated immune responses. Several preclinical and clinical trials were undertaken to explore the possibility to stimulate specific immune responses in chronically infected animals and patients by vaccination. Vaccinations of patients with commercially available HBV vaccines did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed. Some new approaches including DNA vaccines and combinations with antiviral treatments were tested in the woodchuck model. It could be shown that therapeutic vaccinations are able to stimulate specific B- and T-cell responses and to achieve transient suppression of viral replication. These results suggest the great potential of therapeutic vaccination in combination with antivirals to reach an effective and sustained control of HBV infection.