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.

Potential applications:

An AIDS vaccine would be critical in controlling the spread of the epidemic. Although the goal of the project is to induce neutralising antibodies, a successful candidate may be only partially protective. The knowledge accumulated during the first series of testing will set the bases for optimisation of candidates and design of second-generation vaccines.

According to models, even if the UN universal access goals for expanded prevention and treatment are met by 2015 and the number of new infections is reduced, this will not be sufficient to halt the pandemic since 3 million people would still be infected each year by 2015. Modelling shows that even a partially effective vaccine provided to a modest proportion of the population could lead to a major decrease in new HIV infections. Even an AIDS vaccine introduced a decade from now at a time when other prevention and treatment activities have expanded would still make a significant impact. This underscores the importance of sustaining investments and policy efforts to accelerate AIDS vaccine research and development.

Coordinator:

Raphaelle El Habib
sanofi pasteur
Marcy l'Etoile
France
E-mail: raphaelle.elhabib@sanofipasteur.com

Partners: