To Örebro University

Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. Chronic infections with the hepatitis C virus (HCV) can be effectively cured by antivirals. However, the cured patients can be re-infected as they lack protective immune responses. In addition, the relatively high cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect vaccines with high efficiency to control and possibly eradicate Hepatitis viruses globally. The vaccine should induce either, or both, neutralizing antibodies and protective T cell responses. We have developed and utilized flavivirus replicons as delivery system to prime hepatitis-specific T cell responses. We generated subgenomic replicons of Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), and Kunjin virus (KUNV) expressing either a fusion protein between the HCV NS3/4A and a stork hepatitis B virus core or a vaccine candidate gene of HB/DV. Transfection experiments showed that the antigen expression by KUNV and WNV replicons was several folds higher than the antigen expression of control DNA plasmid with CMV promoter. The immunogenicity of these flavivirus replicons was evaluated in mice. The KUNV replicon triggered a potent cellular immune response with respect to priming of HCV NS3/4A-specific T cells as determined by ELISpot, and polyfunctionality. In short, the newly developed KUNV replicon- based vaccine is an attractive candidate to provide protection against hepatitis viruses.