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Molecular Analysis of Hepatitis C Virus Neutralization and Entry For the Development of Novel Antiviral Immunopreventive Strategies

Objective

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease world-wide. HCV-induced end-stage liver disease such as liver cirrhosis and hepatocellular carcinoma represent a major concern in global health. Treatment options for chronic hepatitis C are limited and no vaccine against HCV infection is available. Vaccine development is hampered by several obstacles. High viral variability and escape from host immune responses render antigen selection a major challenge. Antigen selection requires thorough studies to identify conserved T cell and neutralization epitopes and to decipher neutralization mechanisms, aiming to discover the optimal viral target for immune responses counteracting HCV escape strategies. At the same time it is important to develop antigen presentation systems that are efficient in patients with impaired antiviral immune responses, as often observed during chronic hepatitis C. While most vaccine development programs are based on improving HCV cellular immunity, it is essential to associate, in a same vaccine formulation, immunogens able to induce broad spectrums neutralizing and cellular responses. Owing to recent progresses in the field, here we propose a project aiming to overcome the current limitations in vaccine development by addressing the improvement of B cell responses targeting HCV infection. This will be achieved by a detailed investigation of: 1) mechanisms of antibody-mediated neutralization and escape, 2) impact of lipoproteins associating with the viral particle during assembly/release and counteracting neutralization and 3) cell entry steps that can potentially be targeted by antibodies, including those that are not induced naturally. Thus, through the combined expertise of the team in molecular virology, immunology, clinical hepatology and vectorology, we aim to rationalize the development of B cell immunogens and neutralizing antibodies for novel antiviral immunopreventive strategies targeting HCV infection.

Field of science

  • /natural sciences/biological sciences/microbiology/virology
  • /medical and health sciences/basic medicine/immunology
  • /medical and health sciences/clinical medicine/hepatology

Call for proposal

ERC-2008-AdG
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac 101
75654 Paris
France
Activity type
Research Organisations
EU contribution
€ 1 641 000
Principal investigator
François-Loic Cosset (Dr.)
Administrative Contact
Dominique Pella (Mr.)

Beneficiaries (2)

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 1 641 000
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Principal investigator
François-Loic Cosset (Dr.)
Administrative Contact
Dominique Pella (Mr.)
UNIVERSITATSKLINIKUM HEIDELBERG
Germany
EU contribution
€ 806 357
Address
Im Neuenheimer Feld 672
69120 Heidelberg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Thomas Eisenhauer