Perspectives for a vaccine against hepatitis delta virus

Hepatitis delta virus (HDV) causes severe hepatitis in carriers of hepatitis B virus (HBV). In ∼90% of patients, HDV persists together with HBV and causes early development of cirrhosis and liver carcinoma. Worldwide ∼15 million people are coinfected with HBV-HDV. Specific defects in the immune response causing persistence of the virus have not been identified. Several approaches to develop a vaccine to prevent superinfection in the preclinical model of the woodchuck have failed. Recent findings show that a DNA prime and viral vectors boost immunization regimen can induce a HDV specific CD8 T cell response and can prevent HDV infection in simultaneous infection of woodchuck hepatitis virus-HDV. The vaccine-induced specific CD8 T cell response is effective in preventing HDV replication and spread in the liver. However, the perspectives for a HDV vaccine against genotype-1 to prevent superinfection are much less promising. The T-cell response induced by the current DNA prime and viral vector boost immunization in the preclinical woodchuck model seems insufficient to prevent the spread of HDV in chronic HBV carriers. A more potent vaccine and repeated vaccinations are necessary to induce a HDV-specific T-cell response, which may prevent superinfection in HBsAg carriers.