Analysis of the exposure of induced HIV glycoprotein epitopes in a potential HIV pseudovirion vaccine

Vaccine. 2007 Mar 8;25(12):2161-7. doi: 10.1016/j.vaccine.2006.12.014. Epub 2006 Dec 27.

Abstract

Functionally conserved HIV-Env epitopes, which are induced during the process of Env-mediated membrane fusion, represent interesting immunogens, which may elicit broad neutralising antibody responses. In this report, we analyse a pseudovirion (PV)-based HIV vaccine preparation, potentially enriched in such induced Env-conformations. The vaccine has been prepared by mixing and incubating Env-PVs, with incorporated fusion-defective Env, with PVs, which have incorporated functional CD4 and CXCR4 proteins. Here, we demonstrate that three different monoclonal antibodies (CG10, 17b and 48d), recognising a region of gp120 overlapping with the coreceptor binding site, and a further antibody, 8F101, recognising a CD4-induced epitope outside of the coreceptor site, bind to Env molecules in the putative PV vaccine mixture but not at all, or less strongly, to native Env-PVs. In all cases, antibody binding required an interaction of the Env-PVs with CD4 whereas CXCR4 was dispensible. These results confirm that in the PV vaccine preparation, CD4-induced Env epitopes are accessible and that these, as well as other induced epitopes "downstream" from CD4 binding, may function as immunogens to elicit potentially cross-neutralising humoral immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Monoclonal / immunology
  • CD4 Antigens / metabolism
  • Epitopes / genetics
  • Epitopes / immunology*
  • Epitopes / metabolism
  • Glycoproteins / genetics
  • Glycoproteins / immunology*
  • HIV / genetics
  • HIV / immunology*
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology
  • Mice
  • Receptors, CXCR4 / metabolism
  • Recombinant Proteins / immunology
  • Virion / genetics
  • Virion / immunology
  • Virion / metabolism

Substances

  • AIDS Vaccines
  • Antibodies, Monoclonal
  • CD4 Antigens
  • Epitopes
  • Glycoproteins
  • HIV Envelope Protein gp120
  • Receptors, CXCR4
  • Recombinant Proteins