Postdoctoral Scientist - HCV Vaccine Model Development

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road, Oxford

We seek to appoint a part-time (50% funded) Postdoctoral Scientist to assist in the development a new vaccine model for hepatitis C virus (HCV). This will be used to evaluate the immunogenicity and efficacy of a range of novel vectors and immunisation strategies in advance of human trials.

Development of an effective preventative or prophylactic vaccine is a pressing clinical need, both in the UK and worldwide. HCV is a major cause of severe liver disease in the estimated 160 million people infected with the virus. While there is treatment available, conventional therapies based on interferon are effective in only a proportion of those treated while more recently developed antiviral therapy that directly targets the virus is expensive and its use will remain cost-limited for many years. Importantly, such treatments will not stem the spread of HCV and the large numbers of new infections recorded every year; even those who have been effectively treated remain prone to re-infection. HCV also poses a much greater medical problem worldwide where access to treatment will remain limited; HCV-related deaths worldwide exceed 350,000 per year, comparable to those AIDS, TB and malaria.

The development of HCV vaccine has been hampered by a lack of animal models with which to test different types of vaccine. It has also proven exceptionally difficult to develop vaccines that induce long-lived protective immunity - even clearance of natural HCV infection does not protect from subsequent re-infection, quite unlike the situation of poliovirus, measles and hepatitis A virus (as examples) for which effective vaccines have been developed.

The project will investigate the effectiveness of novel vaccines based on the insertion of HCV protein-coding sequences into cytomegalovirus (CMV) or adenovirus (AdV) vectors. Vaccine candidates based on these vectors will be evaluated for immunogenicity and protection from virus challenge using a novel in vitro model. Rodent hepacivirus (RHV) is closely related to HCV, infects rats and causes the same pattern of liver disease and frequency of persistence as HCV in humans. In our planned project, we will develop CMV and AdV vectors containing genes from RHV to directly evaluate whether this approach can generate protective immunity and can clear RHV infection in rats that are chronically infected with the virus. Based on previous experience with CMV/SIV vaccine candidates in macaques, we believe this strategy will also prove effective for HCV and if confirmed, could translate through very rapidly into human clinical trials.

The appointee will be based at the Peter Medawar Building for Pathogen Research in central Oxford. He/she will be supervised by Peter Simmonds (virology), Ellie Barnes (vaccines) and Paul Klenerman (immunology) and be a member of a larger team of scientists with interests in the fields of immunology, vector design and gene expression technologies. There will be close collaborative links, and sharing of expertise, with the Jenner Institute (Oxford) and Michael Jarvis (University of Plymouth, CMV vector design and construction).

Applications for this vacancy are to be made online. You will be required to upload a supporting statement and CV as part of your online application.

Only applications received before 12.00 midday on Monday 5 February 2018 will be considered.

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