IFN-c in the culture supernatants was measured using the Biotrak mouse ELISA system (GE Healthcare). All test samples were assayed in duplicate, and the SD in each test was always ,5% of the mean value.  Therapeutic Vaccination in Chronic Hepatitis B: Preclinical Studies in the Woodchuck Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to a satisfactory result. Induction of HBV-specific T cells by therapeutic vaccination or immunotherapies may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed. The woodchuck (Marmota monax) is a useful preclinical model for developing the new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments with nucleos(t)ide analogues, DNA vaccines, and protein vaccines were tested in the woodchuck model. In this paper we summarize the available data concerning therapeutic immunization and gene therapy using recombinant viral vectors approaches in woodchucks, which show encouraging results. In addition, we present potential innovations in immunomodulatory strategies to be evaluated in this animal model. World Health Organization estimates that about 2 billion people worldwide have been infected with hepatitis B virus (HBV). Since the introduction of preventive vaccination programs against hepatitis B in over 170 countries, the number of new infections is continuously decreasing. Despite the success of prophylactic vaccines, chronic HBV infection is still a global health problem. Over 360 million people are persistently infected with HBV, of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma (HCC). The outcome of HBV infection varies greatly from person to person. In most of the cases the infection is cleared spontaneously, however, 5%-10% of adults develop chronic infection. By contrast, 40%-90% of children which are born to HBV-infected mothers will progress to develop a persistent liver disease [1] . In the recent, years a marked progress has been made in the treatment of chronic hepatitis B. Currently, the two types of antiviral therapies are approved: treatment with pegylated interferon alpha 2a (PEG-IFNα) or nucleos(t)ide analogues, such as adefovir, entecavir (ETV), lamivudine, telbivudine, and tenofovir [2] [3] [4] [5] . However, the efficacy of those therapies in preventing liver cirrhosis and HCC is still limited. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients, regardless of combining the therapy with polymerase inhibitors. On the other hand, the treatment with nucleos(t)ide analogues significantly suppresses HBV replication that leads to a decrease of necroinflammation in the liver. However, those antivirals cannot completely eradicate the virus. After withdrawal of the drug, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drugresistant HBV strains that is often the cause of the therapy failure [6, 7] . Therefore, the new approaches in treating chronic hepatitis B are urgently needed.