Human anti-HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness

J Exp Med. 2010 Aug 30;207(9):1995-2002. doi: 10.1084/jem.20101176. Epub 2010 Aug 2.


The identification and characterization of conserved epitopes on the HIV-1 viral spike that are immunogenic in humans and targeted by neutralizing antibodies is an important step in vaccine design. Antibody cloning experiments revealed that 32% of all HIV-neutralizing antibodies expressed by the memory B cells in patients with high titers of broadly neutralizing antibodies recognize one or more "core" epitopes that were not defined. Here, we show that anti-core antibodies recognize a single conserved epitope on the gp120 subunit. Amino acids D474, M475, R476, which are essential for anti-core antibody binding, form an immunodominant triad at the outer domain/inner domain junction of gp120. The mutation of these residues to alanine impairs viral fusion and fitness. Thus, the core epitope, a frequent target of anti-HIV-neutralizing antibodies, including the broadly neutralizing antibody HJ16, is conserved and indispensible for viral infectivity. We conclude that the core epitope should be considered as a target for vaccine design.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • B-Lymphocytes / immunology
  • Cell Line
  • Epitopes / chemistry
  • Epitopes / immunology*
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1 / chemistry
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Herpesvirus 4, Human / immunology
  • Humans
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary


  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • gp120 protein, Human immunodeficiency virus 1