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The hepatitis c virus is a single-stranded (+)-strant RNA-virus. It belongs to the genus Hepacivirus a member of the family Flaviviridae. It is classified into 6 different genotypes and 30 subtypes with a different geographic distribution.
The infection with HCV can cause an acute hepatitis that can lead to a chronic infection associated with the development of liver cirrhosis and hepatocellular carcinoma HCC). Because of the enormous global meaning, there are currently 170 million people infected with HCV worldwide, the insufficient therapeutic options and the lack of a prophylactic vaccine it would be of great importance to develop an HCV specific vaccine.
This way it would be possible to prevent the spread of HCV-infection with passing into liver cirrhosis and to reach primary prevention against HCVinduces HCCs.
Because it is expected that especially the lack of an efficient t-cell response is responsible for the chronicity of a HCV infection there are increased approaches to develope HCV specific T-cell vaccines.
The aim of this project was to establish more basics for the development of a HCV vaccine.
This has been achieved by cell permeable virus like particles (VLPs) based on the capsid from the hepatitis B virus presenting HCV specific antigens on their surface.
On the one hand the highly ordered structure should induce an efficient humeral immune answer. On the other hand the membrane permeability should allow a transfer of the particles into the cytoplasm and a proteasomal degradation to obtain the efficient loading of MHC class I complexes for the induction of a t-cell mediated immune response. In this work correct assembled cell permeable particles carrying HCV specific antigens were generated and isolated. The ability of membrane permeability could be shown in vitro and in vivo. In further projects it must be investigated in first immunization trials if it is possible to induce an efficient B- and T-cell response. If these tests prove positive in this way produced VLPs were interesting p rophylactic or therapeutic vaccine candidates.