A genetically engineered live-attenuated simian-human immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular immunity in rhesus macaques

Virology. 2007 Apr 25;361(1):68-79. doi: 10.1016/j.virol.2006.10.050. Epub 2006 Dec 8.

Abstract

Regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), a CC-chemokine, enhances antigen-specific T helper (Th) type-1 responses against HIV-1. To evaluate the adjuvant effects of RANTES against HIV vaccine candidate in SHIV-macaque models, we genetically engineered a live-attenuated SHIV to express the RANTES gene (SHIV-RANTES) and characterized the virus's properties in vivo. After the vaccination, the plasma viral loads were same in the SHIV-RANTES-inoculated monkeys and the parental nef-deleted SHIV (SHIV-NI)-inoculated monkeys. SHIV-RANTES provided some immunity in monkeys by remarkably increasing the antigen-specific CD4+ Th cell-proliferative response and by inducing an antigen-specific IFN-gamma ELISpot response. The magnitude of the immunity in SHIV-RANTES-immunized animals, however, failed to afford greater protection against a heterologous pathogenic SHIV (SHIV-C2/1) challenge compared to control SHIV-NI-immunized animals. SHIV-RANTES immunized monkeys, elicited robust cellular CD4+ Th responses and IFN-gamma ELISpot responses after SHIV-C2/1 challenge. These findings suggest that the chemokine RANTES can augment vaccine-elicited, HIV-specific CD4+ T cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology*
  • Acquired Immunodeficiency Syndrome / virology
  • Adjuvants, Immunologic
  • Animals
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / immunology*
  • Chemokine CCL5 / metabolism
  • HIV Antigens / immunology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Interferon-gamma / biosynthesis
  • Macaca mulatta
  • Male
  • Reassortant Viruses / genetics
  • Reassortant Viruses / immunology*
  • Reassortant Viruses / metabolism
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*
  • T-Cell Antigen Receptor Specificity
  • Vaccination*
  • Viral Load

Substances

  • Adjuvants, Immunologic
  • Chemokine CCL5
  • HIV Antigens
  • Interferon-gamma