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Published March 1, 2016 | public
Journal Article

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.

Additional Information

© 2016 Wolters Kluwer Health, Inc. Received for publication February 18, 2015; accepted July 13, 2015. Supported by the Agence Nationale de Recherche sur le SIDA et les Hépatites (ANRS, Paris, France). M. Morgand was supported by a doctoral fellowship from the ANRS. M. Bouvin-Pley was supported by doctoral fellowships from the Région Centre and Sidaction (France). Presented in part as a poster presentation at the "AIDS vaccine 2013" meeting, October 7–9, 2013, Barcelona, Spain. The following reagents were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: TZM-bl cells from John C. Kappes, Xiaoyun Wu, and Tranzyme Inc.; VRC01 and VRC03 from Dr. John Mascola; 10E8 and 35O22 from Dr. Mark Connors. The authors thank Sylvie Brunet for her excellent technical support and Marie Leoz for previous work on isolation and characterization of the viral strains. The authors have no conflicts of interest to disclose.

Additional details

Created:
August 20, 2023
Modified:
October 17, 2023