20170080_0014

© Hubert RAGUET / Institut Cochin / CNRS Images

Reference

20170080_0014

Morgane Bomsel, responsable de l'équipe "Entrée muqueuse du VIH et immunité muqueuse"

Morgane Bomsel, head of the "Mucosal entry of HIV and mucosal immunity" research team. Sexual transmission of the HIV-1 virus chiefly occurs when infected cells in genital fluids come into contact with the surface of the genital mucosa. This intercellular contact, referred to as a viral synapse, induces mass local production of the infectious virus. The virus can then effectively penetrate the tissue, infect the first target immune cells and start forming cell reservoirs. Certain individuals with high exposure to the virus (HESN - highly exposed seronegative), but who are seronegative (no specific virus IgGs in the blood), for reasons that are still poorly understood but which are clearly linked to these repeated infectious exposures, have succeeded in showing an immune response in the mucosa in the form of IgA antibodies, despite the fact that no IgGs against the virus are found in the blood or mucosa. These IgAs recognise the surface of the virus and block infection, protecting these HESN subjects from sexual infection. The "Mucosal entry of HIV and mucosal immunity" team led by Morgane Bomsel has set up an IgA combinatorial library using mucosa samples from HESN women. By characterising the specific nature of these IgAs and their antiviral activities at a cellular level, research scientists are aiming to use them either in passive therapy, through the application of locally protective IgAs in the form of a microbicide before sexual intercourse, or in a vaccine that replicates the production (by the vaccinated individual) of these IgAs that protect the mucosa. A vaccination test in monkeys using a vaccine based on the parts of the virus recognised by these IgAs was found to protect the vaccinated monkeys completely from repeated experimental vaginal infections. These pre-clinical studies were followed by a phase 1 clinical trial in which the vaccine succeeded in inducing IgA antibodies, shown to protect against the virus during in-vitro tests, in the vaccinated women. A clinical study in humans (women and men) on a larger scale using this same vaccine is currently being prepared.

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