Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein

J Exp Med. 2012 Jul 30;209(8):1469-79. doi: 10.1084/jem.20120423. Epub 2012 Jul 23.

Abstract

Two to three years after infection, a fraction of HIV-1-infected individuals develop serologic activity that neutralizes most viral isolates. Broadly neutralizing antibodies that recognize the HIV-1 envelope protein have been isolated from these patients by single-cell sorting and by neutralization screens. Here, we report a new method for anti-HIV-1 antibody isolation based on capturing single B cells that recognize the HIV-1 envelope protein expressed on the surface of transfected cells. Although far less efficient than soluble protein baits, the cell-based capture method identified antibodies that bind to a new broadly neutralizing epitope in the vicinity of the V3 loop and the CD4-induced site (CD4i). The new epitope is expressed on the cell surface form of the HIV-1 spike, but not on soluble forms of the same envelope protein. Moreover, the new antibodies complement the neutralization spectrum of potent broadly neutralizing anti-CD4 binding site (CD4bs) antibodies obtained from the same individual. Thus, combinations of potent broadly neutralizing antibodies with complementary activity can account for the breadth and potency of naturally arising anti-HIV-1 serologic activity. Therefore, vaccines aimed at eliciting anti-HIV-1 serologic breadth and potency should not be limited to single epitopes.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • B-Lymphocytes / immunology
  • Binding Sites, Antibody
  • CD4 Antigens / immunology*
  • Epitopes / immunology*
  • HEK293 Cells
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp160 / immunology
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans

Substances

  • Antibodies, Neutralizing
  • CD4 Antigens
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp160