Extensively cross-reactive anti-HIV-1 neutralizing antibodies induced by gp140 immunization

Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10193-8. doi: 10.1073/pnas.0608635104. Epub 2007 May 31.

Abstract

An immunization regimen was evaluated in rabbits consisting of the soluble, oligomeric form of envelope glycoprotein of HIV-1, strain R2 (gp140(R2)), or the surface component of the same envelope (Env), gp120(R2), in the adjuvant AS02A. The gp140(R2) was selected based on its unusual CD4-independent phenotype and the exceptionally broad neutralizing response in the infected donor. The gp140(R2) immunogen induced antibodies that achieved 50% neutralization of 48/48, and 80% neutralization of 43/46 primary strains of diverse HIV-1 subtypes tested. The strains tested included members of standard panels of subtype B and C strains, and other diverse strains known to be neutralization resistant. The gp120(R2) induced antibodies that neutralized 9/48 of the same strains. Neutralization was IgG-mediated and HIV-1-specific. These results demonstrate that induction of truly broad spectrum neutralizing antibodies is an achievable goal in HIV-1 vaccine development.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Antibody Specificity
  • Cross Reactions
  • Gene Products, env / administration & dosage
  • Gene Products, env / immunology*
  • HIV Antibodies / blood*
  • HIV Antibodies / immunology*
  • HIV Infections / prevention & control*
  • HIV-1 / immunology
  • Humans
  • Immunoglobulin G / blood
  • Neutralization Tests
  • Rabbits
  • Vaccination*
  • env Gene Products, Human Immunodeficiency Virus

Substances

  • Adjuvants, Immunologic
  • Gene Products, env
  • HIV Antibodies
  • Immunoglobulin G
  • env Gene Products, Human Immunodeficiency Virus
  • gp140 envelope protein, Human immunodeficiency virus 1