Elias Honerød Augestad
Native envelope protein trimers as hepatitis C
virus vaccine antigens
Hepatitis C virus (HCV) is a global health concern, with more than 70 million chronically infected worldwide and ~400.000 estimated annual deaths from virus-related liver diseases. The overarching goal of this translational research project is to develop a novel HCV vaccine candidate. As an early induction of broadly neutralizing antibodies (Nabs) is correlated with HCV clearance, the vaccine will be tested in mice for induction of antibodies that are able to neutralize isolates from different genotypes of the virus.
This project is based on the recent major finding in the academic mentor environment that it is possible to isolate the envelope proteins E1/E2 of HCV in a native, trimeric state. The applicant will employ several approaches to optimize and stabilize this trimer as a vaccine antigen, which will be combined with the expertise of the clinical mentor environment in selecting suitable adjuvants for human applications. So far, HCV vaccine studies have typically induced low-level of NAbs, often with poor cross-genotype reactivity. The trimer vaccine is likely to induce an antibody response superior to previously developed recombinant E1/E2 vaccines for HCV, as these have not presented the envelope proteins in their native form.
HCV therapy is only available to a small fraction of infected patients, and very few countries are on track for WHO elimination targets (reducing new viral hepatitis infections by 90% and reduce deaths caused by virus-induced liver disease by 65% by 2030). Consequently, it has become clear that an effective vaccine is needed to control the disease globally. Thus, there is an urgent need for a prophylactic vaccine for global control of the disease. This project has great potential, both in generating high-impact publications and ultimately creating a product that can prevent the deaths and suffering of many people.
Basic mentor: Associate Professor Jannick Prentø, Department of Immunology and Microbiology, UCPH