Paris, 3 August 2011

Hepatitis C : a novel vaccine approach

The development of a vaccine active against hepatitis C: this was the objective of a European study coordinated by David Klatzmann in the Laboratoire Immunologie-Immunopathologie-Immunothérapeutique (CNRS/UPMC/INSERM) and supported by the ANRS. For the first time, scientists have managed to produce, in animals, broad-spectrum antibodies against the hepatitis C virus. Published on 3 August 2011 in Science Translational Medicine, their findings open the way to the development of a vaccine against hepatitis C and, more broadly, towards a new technology for the design of vaccines against other infections (HIV, dengue fever, etc.).

Hepatitis C virus (HCV) infection is a major public health problem, with 200 million chronically infected individuals worldwide and a prevalence of more than 10% to 30% in certain endemic areas. The major complications of HCV infection, such as liver failure and liver cancer, cause about 50,000 deaths worldwide each year. The WHO estimates that without rapid intervention to contain the spread of this disease, the death rate from hepatitis C could exceed that from AIDS in the future. Antiviral therapies are available to eradicate the virus but they are very expensive and little accessible to southern countries, and although there is a clear need for a preventive vaccine, this is not yet available.

In the context of a European study coordinated by David Klatzmann in the Laboratoire Immunologie-Immunopathologie-Immunothérapeutique (CNRS/UPMC/INSERM) and supported by the ANRS, the start-up company Epixis has produced some promising results using a new vaccine development strategy driven by several French research teams(1).

In order to develop a vaccine against HCV, the scientists designed a technology based on the use of pesudotyped virus-like particles. These artificial structures resemble viral particles but are harmless because they contain no genetic material and do not allow the virus to propagate(2). The novelty of the study resides in the development of "chimeric" pseudotyped viral-like particles; i.e. constructed using fragments from two different viruses. In the present case, they are pseudo-particles arising from a mouse retrovirus covered with HCV envelope proteins.

In reaction to immunization with these pseudotyped viral particles, the scientists observed, for the first time, the production of antibodies neutralizing the HCV virus in the mouse and macaque. It is generally accepted that neutralizing antibodies are the principal mediators of protective immunity in most human vaccines.

These same antibodies proved to exert a broad-spectrum activity; i.e. they were able to induce neutralizing immunity against different sub-types of HCV. Until now, all attempts in this respect had failed. These findings are important to the development of a preventive vaccine against hepatitis C virus. More generally, they could be applied to the development of similar strategies for vaccines against other infections such as HIV, dengue and Respiratory Cyncytial Virus (RCV), etc.


© D. Klatzmann/CNRS

Diagram illustrating the chimeric viral pseudo-particles used during the study


This study received support from the ANRS and via a European "CompuVac" research contract funded in the context of the 6th European Framework Program (FP6). It involved 18 European partners, including CNRS, UPMC, ENS Lyon, Institut Pasteur, CEA, INSERM, Université Claude Bernard – Lyon 1 and Epixis.


(1) The following entities were particularly closely involved in this study: teams from the Laboratoire Immunologie-Immunopathologie-Immunothérapeutique (CNRS/UPMC/INSERM), the Laboratoire de Virologie Humaine (INSERM/Université Claude Bernard Lyon 1/ENS Lyon), the Unité de Génomique Virale et Vaccination (CNRS/Institut Pasteur), and the Immunovirology Department (CEA/Université Paris-Sud 11).
(2) The use of pseudotyped viral particles is widely known and applied; for example in the vaccine against papillomavirus.


A Prime-Boost Strategy Using Virus-Like Particles Pseudotyped for HCV Proteins Triggers Broadly Neutralizing Antibodies in Macaques, Pierre Garrone, Anne-Catherine Fluckiger, Philippe E. Mangeot, Emmanuel Gauthier, Pia Dupeyrot-Lacas, Jimmy Mancip, Arnaud Cangialosi, Isaure Du Chéné, Roger LeGrand, Isabelle Mangeot, Dimitri Lavillette, Bertrand Bellier, François-Loïc Cosset, Frederic Tangy, David Klatzmann, Charlotte Dalba.
Science Translational Medicine, 3 August 2011.


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