PhD ceremony: Ms. P.P. Ip, 16.15 uur, Doopsgezinde Kerk, Oude Boteringestraat 33, Groningen
Dissertation: A Candidate Therapeutic Vaccine against Hepatitis C Virus
Promotor(s): prof.dr. C.A.H.H. Daemen, prof.dr. H.W. Nijman, prof.dr. J.C. Wilschut
Faculty: Medical Sciences
Hepatitis C virus (HCV) is a human tumor-associated virus that is transmitted by blood and infects the human liver. The majority of HCV-infected patients (> 70%) does not clear the infection naturally and develops chronic hepatitis, which is associated with the development of liver cirrhosis, liver failure and hepatocellular carcinoma. In patients with a chronic HCV infection a poor and narrow-spectrum cellular immune response against HCV is often observed while in patients who recovered from acute infection the immune responses are broader. Thus, boosting the host’s immune response would be a fundamental therapeutic strategy to eradicate the persisting viruses and halt associated liver diseases.
In this thesis, we studied the development of HCV therapeutic vaccines including (i) generation of HCV vaccines based on a potent viral vector, Semliki Forest virus (SFV), (ii) enhancing the vaccine efficacy the SFV vector and (iii) selection of antigens for a precise vaccine design. We generated three HCV vaccines expressing all or parts of the HCV nonstructural proteins (nsPs) and demonstrated that vaccination with these SFV-based HCV vaccines induced a robust cellular immune response against one nsP. Next, in order to induce strong response against other nsPs, we generated SFV-based vaccines with the inclusion of a carrier protein. We showed that the carrier protein efficiently enhanced the efficacy of the SFV-based vaccines. Last, we identified antigen candidates for vaccine design by using multiple prediction algorithms. Taken together, studies described in this thesis provide a fundamental understanding on the design of highly potent therapeutic HCV vaccines.
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