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EuroNeut-41


EUROpean consortium on NEUTralising antibodies using gp41
 
 
Framework programme:
 7
Contract/Grant agreement number:
201038
EC contribution:
11,966,082 €
Duration:
60 months
Funding scheme:
Collaborative project - Large-scale integrating project
Starting date:
01/01/2008
Project Web site:
http://www.euroneut-41.eu/
 
 

Keywords: HIV, gp41, vaccine, neutralising antibodies, mucosal immunity

Background

There is an increasing body of scientific evidence demonstrating that the binding of small molecular weight compounds, peptides, and antibodies to fusion-intermediate conformations of gp41 leads to an inhibition of cell entry by HIV.

An HIV vaccine should be able to induce neutralising antibodies for inhibiting the virus entry at both sites of infection, i.e. in blood and mucosa. Such a vaccine would produce sterilising immunity. Numerous HIV vaccines under development in the world aim at eliciting cell-mediated immunity. These vaccines should complement the neutralising antibody-inducing vaccines to prevent infection and control viral load.

Aims and expected results

EuroNeut-41 is developing new vaccines able to elicit neutralising antibodies that block entry of HIV into cells, at mucosal sites and in blood. These vaccine candidates will be derived from the envelope of HIV. This envelope mediates viral entry and represents the only viral protein that is targeted by neutralising antibodies. The gp41 trans-membrane region plays a key role in virus entry and displays regions that are well preserved among sub-types. It is expected that antibodies directed against this protein will provide sterilising immunity against a broad range of viruses.

The project will establish a platform where gp41-derived vaccine candidates can be designed for eliciting neutralising antibodies. Several families of immunogens aiming at either mimicking fusion intermediate conformations of gp41 or optimising the exposition of the 2F5/4E10 epitopes are already available and will be optimised during the project. Further antigens will be designed by modelling. Candidates will be submitted to a thorough biophysical characterisation, then to a preclinical development for identifying the most promising candidate for clinical evaluation.

A crucial selection parameter will be the ability of antigens to elicit neutralising antibodies using internationally standardised assays. Since sexual transmission accounts for more than 90% of HIV infection, the capacity of antibodies to inhibit infection at the mucosal level also will be determined. This project is based on rational exploitation of knowledge on the mechanism of HIV entry. As such, it is a promising approach to generation of a protective vaccine. It is the first European project targeting intermediate conformations of gp41 and it will complement other strategies using gp41 or gp140 trimers to induce neutralising antibodies or the approaches aiming at preventing infection and reducing the viral load by eliciting cellular immunity against HIV.

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