V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1

Abstract : Background: Highly potent broadly neutralizing monoclonal antibodies (bNAbs) have been obtained from individuals infected by HIV-1 group M variants. We analyzed the cross-group neutralization potency of these bNAbs toward non-M primary isolates (PI). Material and Methods: The sensitivity to neutralization was analyzed in a neutralization assay using TZM-bl cells. Twenty-three bNAbs were used, including reagents targeting the CD4-binding site, the N160 glycan-V1/V2 site, the N332 glycan-V3 site, the membrane proximal external region of gp41, and complex epitopes spanning both env subunits. Two bispecific antibodies that combine the inhibitory activity of an anti-CD4 with that of PG9 or PG16 bNAbs were included in the study (PG9-iMab and PG16-iMab). Results: Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O PIs, 1 group N PI, and the group P PI were neutralized by PG9 and/or PG16 or PGT145 at low concentrations (0.04–9.39 µg/mL). None of the non-M PIs was neutralized by the bNAbs targeting other regions at the highest concentration tested, except 10E8 that neutralized weakly 2 group N PIs and 35O22 that neutralized 1 group O PI. The bispecific bNAbs neutralized very efficiently all the non-M PIs with IC50 below 1 µg/mL, except 2 group O strains. Conclusion: The N160 glycan-V1/V2 site is the most conserved neutralizing site within the 4 groups of HIV-1. This makes it an interesting target for the development of HIV vaccine immunogens. The corresponding bNAbs may be useful for immunotherapeutic strategies in patients infected by non-M variants.
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Journal of Acquired Immune Deficiency Syndromes, Lippincott, Williams & Wilkins, 2016, 71 (3), pp.237-245. 〈10.1097/QAI.0000000000000854〉
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Contributeur : Frank Thomas <>
Soumis le : mercredi 11 mai 2016 - 10:32:11
Dernière modification le : mercredi 20 juin 2018 - 11:54:02

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Marion Morgand, Mélanie Bouvin-Pley, Jean-Christophe Plantier, Alain Moreau, Elodie Alessandri, et al.. V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1. Journal of Acquired Immune Deficiency Syndromes, Lippincott, Williams & Wilkins, 2016, 71 (3), pp.237-245. 〈10.1097/QAI.0000000000000854〉. 〈hal-01314296〉

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