Identification of Conserved Subdominant HIV Type 1 CD8+ T Cell Epitopes Restricted Within Common HLA Supertypes for Therapeutic HIV Type 1 Vaccines
In: AIDS research and human retroviruses, Jg. 28 (2012), Heft 11, S. 1434-1443
academicJournal
- print, 40 ref
Zugriff:
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.
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Identification of Conserved Subdominant HIV Type 1 CD8+ T Cell Epitopes Restricted Within Common HLA Supertypes for Therapeutic HIV Type 1 Vaccines
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Autor/in / Beteiligte Person: | KARLSSON, Ingrid ; KLØVERPRIS, Henrik ; JARLOV JENSEN, Kristoffer ; STRYHN, Anette ; BUUS, Søren ; KARLSSON, Annika ; VINNER, Lasse ; GOULDER, Philip ; FOMSGAARD, Anders |
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Zeitschrift: | AIDS research and human retroviruses, Jg. 28 (2012), Heft 11, S. 1434-1443 |
Veröffentlichung: | New Rochelle, NY: Liebert, 2012 |
Medientyp: | academicJournal |
Umfang: | print, 40 ref |
ISSN: | 0889-2229 (print) |
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