Fusion-competent vaccines: broad neutralization of primary isolates of HIV

Science. 1999 Jan 15;283(5400):357-62. doi: 10.1126/science.283.5400.357.

Abstract

Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Comment
  • Retracted Publication

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • CD4 Antigens / metabolism
  • Cell Fusion
  • Coculture Techniques
  • Epitopes / immunology
  • Gene Products, env / chemistry
  • Gene Products, env / immunology*
  • Gene Products, env / metabolism
  • Giant Cells
  • HIV Antibodies / biosynthesis
  • HIV Antibodies / immunology*
  • HIV Antigens / chemistry
  • HIV Antigens / immunology*
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / immunology
  • HIV Envelope Protein gp41 / metabolism
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • HIV-1 / physiology
  • Humans
  • Mice
  • Mice, Transgenic
  • Neutralization Tests
  • Protein Conformation
  • Receptors, CCR5 / metabolism
  • Tumor Cells, Cultured

Substances

  • AIDS Vaccines
  • CD4 Antigens
  • Epitopes
  • Gene Products, env
  • HIV Antibodies
  • HIV Antigens
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Receptors, CCR5