Simian immunodeficiency virus SIVmac239Deltanef vaccination elicits different Tat28-35SL8-specific CD8+ T-cell clonotypes compared to a DNA prime/adenovirus type 5 boost regimen in rhesus macaques

J Virol. 2011 Apr;85(7):3683-9. doi: 10.1128/JVI.02112-10. Epub 2011 Jan 26.

Abstract

Different human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccine vectors expressing the same viral antigens can elicit disparate T-cell responses. Within this spectrum, replicating variable vaccines, like SIVmac239Δnef, appear to generate particularly efficacious CD8(+) T-cell responses. Here, we sequenced T-cell receptor β-chain (TRB) gene rearrangements from immunodominant Mamu-A 01-restricted Tat(28-35)SL8-specific CD8(+) T-cell populations together with the corresponding viral epitope in four rhesus macaques during acute SIVmac239Δnef infection. Ultradeep pyrosequencing showed that viral variants arose with identical kinetics in SIVmac239Δnef and pathogenic SIVmac239 infection. Furthermore, distinct Tat(28-35)SL8-specific T-cell receptor (TCR) repertoires were elicited by SIVmac239Δnef compared to those observed following a DNA/Ad5 prime-boost regimen, likely reflecting differences in antigen sequence stability.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Adenoviruses, Human
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Drug Carriers / administration & dosage
  • Gene Products, nef / immunology*
  • Genetic Vectors
  • High-Throughput Nucleotide Sequencing
  • Immunization, Secondary / methods*
  • Macaca mulatta
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • SAIDS Vaccines / administration & dosage
  • SAIDS Vaccines / immunology*
  • Simian Immunodeficiency Virus / immunology*
  • T-Lymphocyte Subsets / immunology
  • Vaccination / methods*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Substances

  • Drug Carriers
  • Gene Products, nef
  • Receptors, Antigen, T-Cell, alpha-beta
  • SAIDS Vaccines
  • Vaccines, DNA
  • Vaccines, Synthetic