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Title: V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1. Author: Morgand M, Bouvin-Pley M, Plantier JC, Moreau A, Alessandri E, Simon F, Pace CS, Pancera M, Ho DD, Poignard P, Bjorkman PJ, Mouquet H, Nussenzweig MC, Kwong PD, Baty D, Chames P, Braibant M, Barin F. Journal: J Acquir Immune Defic Syndr; 2016 Mar 01; 71(3):237-45. PubMed ID: 26413851. 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.[Abstract] [Full Text] [Related] [New Search]