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

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 71; no. 3; p. 237
• Main Authors: Morgand, Marion, Bouvin-Pley, Mélanie, Plantier, Jean-Christophe, Moreau, Alain, Alessandri, Elodie, Simon, François, Pace, Craig S, Pancera, Marie, Ho, David D, Poignard, Pascal, Bjorkman, Pamela J, Mouquet, Hugo, Nussenzweig, Michel C, Kwong, Peter D, Baty, Daniel, Chames, Patrick, Braibant, Martine, Barin, Francis
• Format: Journal Article
• Language: English
• Published: United States 01.03.2016
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; CD4 Antigens; CD4 Lymphocyte Count; Chlorofluorocarbons, Methane; Conserved Sequence; env Gene Products, Human Immunodeficiency Virus - immunology; Epitopes - genetics; Epitopes - immunology; Gene Expression Regulation, Viral - physiology; HIV Antibodies - immunology; HIV Envelope Protein gp120 - immunology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - classification; HIV-1 - genetics; HIV-1 - immunology; Humans; Molecular Sequence Data; Phylogeny; Recombinant Proteins
• ISSN: 1944-7884
• DOI: 10.1097/QAI.0000000000000854

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). 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). 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. 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.