Characterization of a Large Panel of Rabbit Monoclonal Antibodies against HIV-1 gp120 and Isolation of Novel Neutralizing Antibodies against the V3 Loop

PLoS One. 2015 Jun 3;10(6):e0128823. doi: 10.1371/journal.pone.0128823. eCollection 2015.

Abstract

We recently reported the induction of potent, cross-clade neutralizing antibodies (nAbs) against Human Immunodeficiency Virus type-1 (HIV-1) in rabbits using gp120 based on an M-group consensus sequence. To better characterize these antibodies, 93 hybridomas were generated, which represent the largest panel of monoclonal antibodies (mAbs) ever generated from a vaccinated rabbit. The single most frequently recognized epitope of the isolated mAbs was at the very C-terminal end of the protein (APTKAKRRVVEREKR), followed by the V3 loop. A total of seven anti-V3 loop mAbs were isolated, two of which (10A3 and 10A37) exhibited neutralizing activity. In contrast to 10A3 and most other anti-V3 loop nAbs, 10A37 was atypical with its epitope positioned more towards the C-terminal half of the loop. To our knowledge, 10A37 is the most potent and broadly neutralizing anti-V3 loop mAb induced by vaccination. Interestingly, all seven anti-V3 loop mAbs competed with PGT121, suggesting a possibility that early induction of potent anti-V3 loop antibodies could prevent induction of more broadly neutralizing PGT121-like antibodies that target the conserved base of the V3 loop stem.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / isolation & purification
  • Binding Sites, Antibody
  • Conserved Sequence
  • Epitopes / chemistry*
  • Epitopes / immunology
  • Female
  • HIV Antibodies / biosynthesis
  • HIV Antibodies / chemistry*
  • HIV Antibodies / isolation & purification
  • HIV Envelope Protein gp120 / administration & dosage
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / immunology
  • HIV-1 / chemistry*
  • HIV-1 / immunology
  • Hybridomas / immunology
  • Models, Molecular
  • Molecular Sequence Data
  • Neutralization Tests
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rabbits
  • Vaccination

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120