Immunomodulation as an option for the treatment of chronic hepatitis B virus infection: preclinical studies in the woodchuck model

Abstract

New therapeutic approaches for chronic hepatitis B virus infection based on immunomodulation are now under investigation. The woodchuck model for hepatitis B virus infection has emerged as a useful animal model for the evaluation of such approaches, after developing necessary assays and reagents for immunologic studies in this model. Conventional and novel vaccines such as DNA vaccines were tested in woodchucks for their ability to induce protective immune responses against challenge infection with the woodchuck hepatitis virus (WHV). Furthermore, immunotherapeutic approaches for the control of chronic hepadnaviral infection were evaluated in woodchucks. Immunizations with WHV proteins and DNA vaccines led to the development of antibodies to the WHV surface antigen and to a significant decrease of viral load in chronically WHV-infected woodchucks. Viral vector-mediated gene transfer was explored for the delivery of antiviral cytokines IFN-alpha in woodchucks and resulted in the decrease of viral replication. It is now generally accepted that a combination of antiviral treatment and immunization will be necessary to achieve successful immunomodulation with a long-term control of chronic hepatitis B virus infection.