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Research Report 1: HCV antigen design: Epitope prediction, evaluation and enhancement

Vlaming, M.R. (2015) Research Report 1: HCV antigen design: Epitope prediction, evaluation and enhancement. Master's Thesis / Essay, Biology.

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Hepatitis C virus (HCV) causes a persistent infection in approximately two-third of the people who contact the virus, resulting in almost 130–150 million infected people worldwide being approximately 3% of the world population. HCV is characterized by the lack of a proofreading mechanism and specifically targeting the liver in which it can cause cirrhosis and/or fibrosis, liver failure and hepatocellular carcinoma. Consequently it is the leading cause for liver transplantation in the western world. Despite improved clinical treatment options, a strategy that not only clears the virus but also induces a memory response against it is warranted. In order to provoke a specific immunological reaction towards HCV infected cells, previous studies examined the HCV genome and pointed out specific epitopes located in the HCV polyprotein which are processed by MHC I. Recent literature also suggests that MHC II epitopes in close proximity or overlapping with MHCI epitopes could play a role in the elicited immunological response. For this reason we identified and compared strong HCV epitopes for MHC I as well as MHC II by theoretical algorithms. Good animal HCV models are lacking because mice do not support HCV infections naturally. Therefore we also wanted to further optimize an existing in vitro T-cell activation model to test the immunogenicity of predicted HCV epitopes. Recently, P.P. Ip et al. developed an alphavirus-based human HPV vaccine which also contains a helper epitope and an ER targeting signal which strongly enhances the immunogenicity of the vaccine. Remarkably these constructs do not strengthen the elicited response when inserted in a HCV vaccine construct. For this reason we wanted to examine the immunogenicity increasing properties of the helper epitope and the ER targeting signal as encoded by the HPV vaccine, in combination with a rSFV-HCV vaccine. In this study we identified several strong immunogenic HCV epitopes by theoretical epitope prediction and tested the immunogenicity in an in vitro model. This model was able to reveal promising immunogenic differences between the predicted epitopes. This model requires further optimization before being reliable enough for an intermediate step between animal models and clinical trials. Also, helper sequences do not appear to be universal applicable for enhancing the immunogenicity of rSFV vaccine constructs.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biology
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 08:06
Last Modified: 15 Feb 2018 08:06

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