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Vaccine design for hepatitis C virus

Hepatitis C (HCV) is an inflammatory blood borne disease that will affect some 0.4-2% of the world's population. For almost half of these, it will evolve into a chronic condition and in 20% of these chronic cases, leads to liver cirrhosis. Moreover, HCV causes hepatocellular carcinoma. Through the analysis of the HCV specific immune response a new strategy that aids the design of a vaccine against the HCV has been developed.

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HCV, a RNA virus, has a high degree of sequence variability among different genotypes. In studying its activity researchers therefore have had great difficulty in activating and expanding cytotoxic T-lymphosytes (CTL) in-vitro, in order to mimic antigen presentation to CTL occurring during natural infection. At the same time, primary infected hepatocytes cannot be used as stimulator/target cells for CTL analysis. Therefore, a group of experts focused their efforts primarily on the specification of the components involved in the protective immunity for the development of vaccine strategies, outlining the factors that potentially affect viral clearance and liver disease. The role that the immune response plays in the course of HCV infection is an undiscovered mystery for scientists, who need also to decide whether the antigenic variation found among different HCV genotypes contributes to the pathogenesis of hepatitis C. Therefore, the team proceeded to characterise the immune response to the different HCV proteins for two subject groups: patients with acute infection who recovered and those who develop a chronic infection. Hence, the team succeeded in assessing the immune response in both cases, namely viral clearance and pathogenesis of liver disease. During these studies, the team identified the antigenic specificity and effector functions of both HLA class I and class II restricted T cell responses to HCV in the peripheral blood and in the liver and conducted a quantitative (ELISA) and a qualitative (neutralisation) analysis of the aspects of the serum antibody responses to HCV. The preceding studies resulted in an efficient mapping of amino acid sequences (epitopes) within the various HCV antigens, which are responsible for T and B cell responses in the course of acute and chronic HCV infection. In addition the team managed to identify the way that these responses affect viral clearance and disease activity. Therefore, the relationship between viral sequence variable and viral persistence as well as disease pathogenesis is now better understood. The results of these studies are very beneficial to many fields, including Immunology Medicine, Biotechnology Pharmaceutical industries, since they present are exploitable for the design of vaccines effective in populations with different HLA backgrounds. Moreover, characterisation of the immune sensitivity to the different HCV antigens can also be manipulated for the design of effective preventive strategies against HCV infection.

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