NOVEL PRIME-BOOST STRATEGIES USING VACCINES FROM DNA LAUNCHED SUICIDAL FLAVIVIRUSES

Hepatitis B virus (HBV), Hepatitis D virus (HDV), and Hepatitis C virus (HCV) infections constitute a major global health problem causing chronic liver disease. These infections are also a major factor underlying liver cirrhosis and hepatocellular carcinoma (HCC), which justifies treatment despite high costs side effects. Although these infections all involve the liver, they require different vaccine strategies for prevention and/or treatment. For HCV, a preventive vaccine strategy will contain the genetically stable non-structural proteins to induce protective T cell responses. For HBV and HDV, a therapeutic vaccine will contain conserved parts of the HBV envelope and the HDV antigen (HDAg) which would induce both neutralizing antibodies and HBV- and HDV-specific T cells. We will here develop both prophylactic and therapeutic hepatitis vaccines exploring the use of Echericiha coli derived proteins used in combination with our newly developed flaviviral DNA replicon vaccine candidates. The use of E. coli-derived proteins and DNA as vaccine platforms are highly attractive from an industrial perspective since these molecules are easy and cheap to produce with excellent stability. These intrinsic characteristics make E. coli expressed proteins and plasmid DNA replicons highly suitable for large-scale vaccinations under simple conditions.