title: Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines.
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.
authors: Department of Virology, Statens Serum Institut, Copenhagen, Denmark.
authors: Ingrid
authors: I
authors: Karlsson
authors: Henrik
authors: H
authors: Kløverpris
authors: Kristoffer Jarlov
authors: KJ
authors: Jensen
authors: Anette
authors: A
authors: Stryhn
authors: Søren
authors: S
authors: Buus
authors: Annika
authors: A
authors: Karlsson
authors: Lasse
authors: L
authors: Vinner
authors: Philip
authors: P
authors: Goulder
authors: Anders
authors: A
authors: Fomsgaard
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003718:Denmark / Q000453:epidemiology; D004353:Drug Evaluation, Preclinical; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006169:Guinea-Bissau / Q000453:epidemiology; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D016415:Sequence Alignment; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D019444:Vaccines, DNA