Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes

Nat Med. 2001 Nov;7(11):1225-31. doi: 10.1038/nm1101-1225.

Abstract

The antigenic polymorphism of HIV-1 is a major obstacle in developing an effective vaccine. Accordingly, we screened random peptide libraries (RPLs) displayed on phage with antibodies from HIV-infected individuals and identified an array of HIV-specific epitopes that behave as antigenic mimics of conformational epitopes of gp120 and gp41 proteins. We report that the selected epitopes are shared by a collection of HIV-1 isolates of clades A-F. The phage-borne epitopes are immunogenic in rhesus macaques, where they elicit envelope-specific antibody responses. Upon intravenous challenge with 60 MID50 of pathogenic SHIV-89.6PD, all monkeys became infected; however, in contrast to the naive and mock-immunized monkeys, four of five mimotope-immunized monkeys experienced lower levels of peak viremia, followed by viral set points of undetectable or transient levels of viremia and a mild decline of CD4+ T cells, and were protected from progression to AIDS-like illness. These results provide a new approach to the design of broadly protective HIV-1 vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology
  • AIDS Vaccines / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Epitopes / administration & dosage
  • Epitopes / genetics
  • HIV Antibodies / biosynthesis
  • HIV Antigens / administration & dosage
  • HIV Antigens / genetics
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Macaca mulatta
  • Peptide Library
  • SAIDS Vaccines / genetics
  • SAIDS Vaccines / immunology
  • SAIDS Vaccines / pharmacology
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*

Substances

  • AIDS Vaccines
  • Epitopes
  • HIV Antibodies
  • HIV Antigens
  • Peptide Library
  • SAIDS Vaccines