PhD Student Position available at the University of Tours, Loire Valley, France
INSERM Unit U966: http://mavivh.univ-tours.fr/home/
Although the recent introduction of direct-acting antiviral agents has considerably improved the treatment of chronic hepatitis C virus (HCV) infection, the eradication of this viral disease is hampered by most HCV-infected subjects being unaware of their infection status and the very high cost of the new treatments, which are unaffordable in lower-income countries. As it is estimated that nearly four million new HCV infections occur each year, the development of an effective and affordable prophylactic vaccine has thus become a major medical priority, providing the best long-term hope for controlling the global epidemic, thereby decreasing the burden on healthcare systems.
With this aim, our team U966 has developed an original vaccination concept based on full-length genotype 1a HCV envelope glycoproteins fused to the heterologous hepatitis B (HBV) envelope protein and self-assembling into highly immunogenic, noninfectious and secreted subviral envelope particles resembling the HBV vaccine. These particles bearing E1 and E2 HCV envelope proteins have been shown to elicit in immunized animals specific antibody responses to the HCV and HBV envelope proteins, and especially strong dual anti-E1 and anti-E2 responses neutralizing efficiently in vitro heterologous strains of the HCV 1a genotype. However, these antibodies appeared to have a lower cross-neutralizing potential against other genotypes.
The objective of the PhD thesis project will be to try to increase the broad neutralizing properties of antibodies induced by our vaccine particles by two complementary approaches: (i) immunize with a cocktail of vaccine particles bearing HCV envelope proteins from different HCV genotypes, or proceed to sequential immunizations with these vaccine particles to favor the induction of antibodies against conserved epitopes ; (ii) as apolipoprotein E (apoE) has been shown to play a functional role in viral evasion from host neutralizing antibodies, we also plan to improve the mode of processing and presenting of our immunogens, especially in trying to mimic precisely epitopes at the HCV envelope proteins/apoE interface.
A Master Degree in cellular and molecular biology is required.
Please apply via email to : firstname.lastname@example.org