Broad neutralization of human immunodeficiency virus type 1 (HIV-1) elicited from human rhinoviruses that display the HIV-1 gp41 ELDKWA epitope

J Virol. 2009 May;83(10):5087-100. doi: 10.1128/JVI.00184-09. Epub 2009 Mar 11.

Abstract

In efforts to develop AIDS vaccine components, we generated combinatorial libraries of recombinant human rhinoviruses that display the well-conserved ELDKWA epitope of the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41. The broadly neutralizing human monoclonal antibody 2F5 was used to select for viruses whose ELDKWA conformations resemble those of HIV. Immunization of guinea pigs with different chimeras, some boosted with ELDKWA-based peptides, elicited antibodies capable of neutralizing HIV-1 pseudoviruses of diverse subtypes and coreceptor usages. These recombinant immunogens are the first reported that elicit broad, albeit modest, neutralization of HIV-1 using an ELDKWA-based epitope and are among the few reported that elicit broad neutralization directed against any recombinant HIV epitope, providing a critical advance in developing effective AIDS vaccine components.

Publication types

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

MeSH terms

  • AIDS Vaccines / immunology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Viral / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology*
  • Guinea Pigs
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp41 / immunology*
  • HIV-1 / immunology*
  • HeLa Cells
  • Humans
  • Immunoglobulin G / immunology
  • Male
  • Neutralization Tests
  • Peptide Library
  • Protein Engineering
  • Rhinovirus / genetics

Substances

  • AIDS Vaccines
  • Antibodies, Monoclonal
  • Antigens, Viral
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • Immunoglobulin G
  • Peptide Library
  • gp41 protein, Human immunodeficiency virus 1