Broadly neutralizing antibodies suppress post-transcytosis HIV-1 infectivity

Abstract : Broadly neutralizing antibodies (bNAbs) offer promising opportunities for preventing HIV-1 infection in humans. Immunoprophylaxis with potent bNAbs efficiently protects non-human primates from mucosal transmission even after repeated challenges. However, the precise mechanisms of bNAb-mediated viral inhibition in mucosal tissues are currently unknown. Here, we show that immunoglobulin (Ig)G and IgA bNAbs do not interfere with the endocytic transport of HIV-1 across epithelial cells, a process referred to as transcytosis. Instead, both viruses and antibodies are translocated to the basal pole of epithelial cells, possibly in the form of an immune complex. Importantly, as opposed to free virions, viral particles bound by bNAbs are no longer infectious after transepithelial transit. Post-transcytosis neutralization activity of bNAbs displays comparable inhibitory concentrations as those measured in classical neutralization assays. Thus, bNAbs do not block the transport of incoming HIV-1 viruses across the mucosal epithelium but rather neutralize the transcytosed virions, highlighting their efficient prophylactic and protective activity in vivo.
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Article dans une revue
Mucosal Immunology, Nature Pub. Group, 2016, 〈10.1038/mi.2016.106〉
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01417469
Contributeur : Anne Lassailly-Bondaz <>
Soumis le : jeudi 15 décembre 2016 - 16:20:58
Dernière modification le : jeudi 11 janvier 2018 - 06:21:37

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Valérie Lorin, M Malbec, C Eden, T Bruel, F Porrot, et al.. Broadly neutralizing antibodies suppress post-transcytosis HIV-1 infectivity. Mucosal Immunology, Nature Pub. Group, 2016, 〈10.1038/mi.2016.106〉. 〈pasteur-01417469〉

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