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Contenido archivado el 2024-05-14

Definition of the mechanism of antibody-mediated influenza virus infectivity neutralisation with a view to improving the efficacy of vaccination

Objetivo

This project is concerned with the strategies for protection against influenza virus and has two main objectives:
- to use monoclonal antibodies of defined specificity to characterise with a view to optimising the protective immune response to vaccination;
- to understand how antibodies neutralise influenza virus infectivity.

The outstanding characteristic of influenza viruses is their ability to cause frequent epidemics of respiratory disease; each outbreak is caused by an antigenically distinct virus. Protection against influenza is mainly achieved by vaccination; the target in this approach is the hemagglutinin (HA), a viral membrane glycoprotein with which neutralising antibodies react. The main objective of this project, potentially of direct practical interest, is to gain a better understanding at the molecular level of the strategy for vaccination against influenza. This is made possible by recent advances in the functional and structural characterisation of influenza HA.

Specific goals include :
-Defining the 3-D structure of epitopes recognised by antibodies specific for the antigenic sites of HA, by determining the X-Ray structures of the complexes of these antibodies with HA.
-Characterising the mechanism of neutralisation by antibodies of structurally defined specificity.
-Comparing the potential for protection of antibodies specific for the different antigenic sites of influenza hemagglutinin.
-Comparing the HA-recognition specificity of neutralising antibodies elicited post-vaccination and in individuals recovering from infection.

Although the available vaccines induce good levels of antibodies, their overall protective efficacy against influenza disease is only about 70 per cent. The results of this project will inform decisions on vaccination regimens that are needed to improve the present situation.

The outstanding characteristic of influenza viruses is their ability to cause frequent epidemics of respiratory disease; anantigenically distinct virus causes each outbreak. Protection against influenza is mainly achieved by vaccination the target in this approach is the hemagglutinin (HA), a viral membrane glycoprotein with which neutralizing antibodies react. The main objective of this project, potentially of direct practical interest, is to gain a better understanding at the molecular level of the strategy for vaccination against influenza. This is made possible by recent advances in the functional and structural characterization of influenza HA.

Specific goals include:- Defining the 3-D structure of epitopes recognized by antibodies specific for the antigenic sites of HA, by determining the X-Ray structures of the complex of these antibodies with HA. -Characterising the mechanism of neutralization by antibodies of structurally defined specificity. -Comparing the potential for protection of antibodies specific for the different antigenic sites of influenza haemaglutinin. -Comparing the HA-recognition specificity of neutralizing antibodies elicited post-vaccination and in individuals recovering from infection. Although the available vaccines induce good levels of antibodies, their overall protective efficacy against influenza disease is only about 70 percent. The results of this project will inform decisions on vaccination regimens that are needed to improve the present situation.

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Coordinador

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
Aportación de la UE
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Avenue de la Terrasse 1, CNRS Batiment 34
91198 GIF SUR YVETTE
Francia

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