Abrogation of AIDS vaccine-induced cytotoxic T-lymphocyte efficacy in vivo due to a change in viral epitope flanking sequences

Microbes Infect. 2008 Mar;10(3):285-92. doi: 10.1016/j.micinf.2007.12.002. Epub 2007 Dec 8.

Abstract

A current promising AIDS vaccine strategy is to elicit CD8(+) cytotoxic T lymphocyte (CTL) responses that broadly recognize highly-diversified HIVs. In our previous vaccine trial eliciting simian immunodeficiency virus (SIV) mac239 Gag-specific CTL responses, a group of Burmese rhesus macaques possessing a major histocompatibility complex haplotype 90-120-Ia have shown vaccine-based viral control against a homologous SIVmac239 challenge. Vaccine-induced Gag(206-216) epitope-specific CTL responses exerted strong selective pressure on the virus in this control. Here, we have evaluated in vivo efficacy of vaccine-induced Gag(206-216)-specific CTL responses in two 90-120-Ia-positive macaques against challenge with a heterologous SIVsmE543-3 that has the same Gag(206-216) epitope sequence with SIVmac239. Despite efficient Gag(206-216)-specific CTL induction by vaccination, both vaccinees failed to control SIVsmE543-3 replication and neither of them showed mutations within the Gag(206-216) epitope. Further analysis indicated that Gag(206-216)-specific CTLs failed to show responses against SIVsmE543-3 infection due to a change from aspartate to glutamate at Gag residue 205 immediately preceding the amino terminus of Gag(206-216) epitope. Our results suggest that even vaccine-induced CTL efficacy can be abrogated by a single amino acid change in viral epitope flanking region, underlining the influence of viral epitope flanking sequences on CTL-based AIDS vaccine efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Cells, Cultured
  • Epitopes, T-Lymphocyte / genetics*
  • Gene Products, gag / immunology
  • Immunization, Secondary
  • Injections, Intramuscular
  • Leukocytes, Mononuclear
  • Macaca mulatta
  • Molecular Sequence Data
  • SAIDS Vaccines / administration & dosage
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Immunodeficiency Virus / physiology*
  • Species Specificity
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccination*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology
  • Virus Replication

Substances

  • Epitopes, T-Lymphocyte
  • Gene Products, gag
  • SAIDS Vaccines
  • Vaccines, DNA