Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines

AIDS Res Hum Retroviruses. 2012 Nov;28(11):1434-43. doi: 10.1089/aid.2012.0081. Epub 2012 Aug 14.

Abstract

The high HIV-1 prevalence, up to 4.6% in Guinea-Bissau, West Africa, makes it a relevant location for testing of therapeutic vaccines. With the aim of performing a clinical study in Guinea-Bissau, after first testing the vaccine for safety in Denmark, Europe, we here describe the design of a universal epitope peptide-based T cell vaccine with relevance for any geographic locations. The two major obstacles when designing such a vaccine are the high diversities of the HIV-1 genome and of the human major histocompatibility complex (MHC) class I. We selected 15 CD8-restricted epitopes predicted from conserved regions of HIV-1 that were subdominant (i.e., infrequently targeted) within natural infections. Moreover, the epitopes were predicted to be restricted to at least one of the five common HLA supertypes (HLA-A01, A02, A03, B07, and B44). Here, we validated the resulting peptide-specific, HLA-restricted T cell specificities using peptide-MHC class I tetramer labeling of CD8(+) T cells from HIV-1-infected individuals. The selected vaccine epitopes are infrequently targeted in HIV-1-infected individuals from both locations. Moreover, we HLA-typed HIV-1-infected individuals and demonstrated that the selected vaccine epitopes, when targeted, are restricted to the five most common HLA supertypes at both locations. Thus, the HLA supertype-directed approach achieved HLA coverage of 95% and 100% of the examined cohorts in Guinea-Bissau and Denmark, respectively. In conclusion, the selected vaccine epitopes match the host populations and HIV-1 strains of these two distant geographic regions, justifying clinical testing in both locations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • AIDS Vaccines* / immunology
  • Adolescent
  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Denmark / epidemiology
  • Drug Evaluation, Preclinical
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Guinea-Bissau / epidemiology
  • HIV Infections / epidemiology
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / immunology*
  • HLA Antigens / immunology*
  • Histocompatibility Testing
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Predictive Value of Tests
  • Sequence Alignment
  • Vaccines, DNA* / immunology

Substances

  • AIDS Vaccines
  • Epitopes, T-Lymphocyte
  • HLA Antigens
  • Vaccines, DNA