title: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *Université François Rabelais, Inserm U966, Tours, France; †Université de Rouen and CHU Charles Nicolle, Rouen, France; ‡Laboratoire de Virologie, Hôpital St Louis, Paris, France; §Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY; ‖Vaccine Research Center, National Institutes of Health, Bethesda, MD; ¶Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA; #California Institute of Technology, CA; **Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France; ††Howard Hughes Medical Institute, The Rockefeller University, New York, NY; ‡‡CRCM, Inserm U1068; Institut Paoli-Calmettes; CNRS UMR7258; AMU UM105; Marseille, France; and §§Laboratoire de Bactériologie-Virologie, Centre National de Référence du VIH, CHU Bretonneau, Tours, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Morgand
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bouvin-Pley
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Plantier
authors.forename: Alain
authors.initials: A
authors.lastname: Moreau
authors.forename: Elodie
authors.initials: E
authors.lastname: Alessandri
authors.forename: François
authors.initials: F
authors.lastname: Simon
authors.forename: Craig S
authors.initials: CS
authors.lastname: Pace
authors.forename: Marie
authors.initials: M
authors.lastname: Pancera
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.forename: Pascal
authors.initials: P
authors.lastname: Poignard
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: Daniel
authors.initials: D
authors.lastname: Baty
authors.forename: Patrick
authors.initials: P
authors.lastname: Chames
authors.forename: Martine
authors.initials: M
authors.lastname: Braibant
authors.forename: Francis
authors.initials: F
authors.lastname: Barin
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D015704:CD4 Antigens; D018791:CD4 Lymphocyte Count; D005617:Chlorofluorocarbons, Methane; D017124:Conserved Sequence; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D005617:Chlorofluorocarbons, Methane; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C076613:recombinant soluble CD4; C005848:trichlorofluoromethane