Analysis of HIV-1 subtype B third variable region peptide motifs for induction of neutralizing antibodies against HIV-1 primary isolates

Virology. 2006 Feb 5;345(1):44-55. doi: 10.1016/j.virol.2005.08.042. Epub 2005 Oct 20.

Abstract

The HIV-1 gp120 V3 loop is a potent inducer of neutralizing antibodies for T cell line adapted-HIV-1, but less so for primary isolates. We hypothesized that peptides representative of the diversity of natural HIV-1 V3 loop variants might capture elements of conserved higher order structures and so stimulate broadly reactive neutralizing antibodies. We designed a panel of 29 subtype B V3 sequences postulated to reflect the range of V3 diversity. These peptides were used to immunize guinea pigs. The most effective peptide (62.19) clustered around the subtype B consensus sequence and induced antibodies that reproducibly neutralized 31% of the subtype B HIV-1 primary isolates evaluated, but exhibited limited cross-neutralization of non-subtype B HIV-1 strains. Taken together, these data demonstrated that the limited neutralization profile of antibodies induced by optimal subtype B V3 motifs likely represents the maximum breadth of neutralization of subtype B HIV-1 primary isolates attainable by anti-V3 peptide antibodies.

Publication types

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

MeSH terms

  • Amino Acid Motifs / immunology
  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Blotting, Western
  • Consensus Sequence
  • Cross Reactions
  • Guinea Pigs
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1 / immunology*
  • Humans
  • Neutralization Tests
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / immunology*
  • Sequence Homology, Amino Acid

Substances

  • Antibodies, Viral
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments