Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex

Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17624-9. doi: 10.1073/pnas.1415789111. Epub 2014 Nov 24.


Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named "PGDM1400-1412," show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 µg/mL. Overall, our results highlight the utility of BG505 SOSIP.664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family.

Keywords: B cell; BG505 SOSIP; HIV; broadly neutralizing antibodies; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Neutralizing / immunology*
  • B-Lymphocytes / immunology
  • Base Sequence
  • Cross Reactions
  • Epitopes / chemistry
  • Genetic Variation
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / immunology
  • Humans
  • Immunologic Memory
  • Inhibitory Concentration 50
  • Leukocytes, Mononuclear / cytology
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Neutralization Tests
  • Peptide Library
  • Phylogeny
  • Protein Folding
  • Recombinant Proteins / immunology
  • Sequence Homology, Amino Acid


  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Peptide Library
  • Recombinant Proteins

Associated data

  • GENBANK/KP006370
  • GENBANK/KP006371
  • GENBANK/KP006372
  • GENBANK/KP006373
  • GENBANK/KP006374
  • GENBANK/KP006375
  • GENBANK/KP006376
  • GENBANK/KP006377
  • GENBANK/KP006378
  • GENBANK/KP006379
  • GENBANK/KP006380
  • GENBANK/KP006381
  • GENBANK/KP006382
  • GENBANK/KP006383
  • GENBANK/KP006384
  • GENBANK/KP006385
  • GENBANK/KP006386
  • GENBANK/KP006387
  • GENBANK/KP006388
  • GENBANK/KP006389
  • GENBANK/KP006390
  • GENBANK/KP006391
  • GENBANK/KP006392
  • GENBANK/KP006393
  • GENBANK/KP006394
  • GENBANK/KP006395
  • PDB/4RQQ