Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells

J Immunol. 2011 Jun 15;186(12):6914-24. doi: 10.4049/jimmunol.1004231. Epub 2011 May 16.

Abstract

Polyvalent mosaic HIV immunogens offer a potential solution for generating vaccines that can elicit immune responses against genetically diverse viruses. However, it is unclear whether key T cell epitopes can be processed and presented from these synthetic Ags and recognized by epitope-specific human T cells. In this study, we tested the ability of mosaic HIV immunogens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors to process and present major HIV clade B and clade C CD8 T cell epitopes in human cells. A bivalent mosaic vaccine expressing HIV Gag sequences was used to transduce PBMCs from 12 HIV-1-infected individuals from the United States and 10 HIV-1-infected individuals from South Africa; intracellular cytokine staining, together with tetramer staining, was used to assess the ability of mosaic Gag Ags to stimulate pre-existing memory responses compared with natural clade B and C vectors. Mosaic Gag Ags expressed all eight clade B epitopes tested in 12 United States subjects and all 5 clade C epitopes tested in 10 South African subjects. Overall, the magnitude of cytokine production induced by stimulation with mosaic Ags was comparable to clade B and clade C Ags tested, but the mosaic Ags elicited greater cross-clade recognition. Additionally, mosaic Ags induced HIV-specific CD4 T cell responses. Our studies demonstrate that mosaic Ags express major clade B and clade C viral T cell epitopes in human cells, as well as support the evaluation of mosaic HIV-1 vaccines in humans.

Publication types

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

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Adenoviridae / genetics
  • Antigen Presentation / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cross Reactions / immunology
  • Gene Products, gag / administration & dosage
  • Gene Products, gag / immunology*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • HIV-1 / immunology
  • Humans
  • South Africa
  • Species Specificity
  • United States

Substances

  • AIDS Vaccines
  • Gene Products, gag