Therapeutic vaccination in chronic hepatitis B virus carriers

Despite effective prophylactic vaccines against hepatitis B virus existing for over 20 years, more than 2.5 billion people worldwide have been exposed to the disease and approximately 370 million people are chronically infected with it. Chronic infection in more than two thirds of infected patients results in chronic liver disease, which may lead to cirrhosis, exposure to noncarcinomatous complications and hepatocellular carcinoma. Currently available therapies fail to allow complete control of viral replication in most patients. Viral persistence has been associated with a defect in the development of hepatitis B virus-specific cellular immunity. Immunomodulatory strategies to boost or to broaden the weak virus-specific T-cell response have been proposed to bypass the chronic hepatitis B infection, including hepatitis B virus envelope- and nucleocapsid-based vaccines, and new formulations for recombinant and DNA-based vaccines, which are currently being evaluated in clinical trials.