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

J Acquir Immune Defic Syndr. 2016 Mar 1;71(3):237-45. doi: 10.1097/QAI.0000000000000854.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology*
  • CD4 Antigens
  • CD4 Lymphocyte Count
  • Chlorofluorocarbons, Methane
  • Conserved Sequence*
  • 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
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • CD4 Antigens
  • Chlorofluorocarbons, Methane
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Recombinant Proteins
  • env Gene Products, Human Immunodeficiency Virus
  • recombinant soluble CD4
  • trichlorofluoromethane