Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | AIDS Research and Human Retroviruses |
Volume | 28 |
Issue number | 11 |
Pages (from-to) | 1434-1443 |
Number of pages | 10 |
ISSN | 0889-2229 |
DOIs | |
Publication status | Published - Nov 2012 |
- AIDS Vaccines, Adolescent, Adult, CD8-Positive T-Lymphocytes, Denmark, Drug Evaluation, Preclinical, Epitopes, T-Lymphocyte, Female, Guinea-Bissau, HIV Infections, HIV-1, HLA Antigens, Histocompatibility Testing, Humans, Male, Middle Aged, Molecular Sequence Data, Predictive Value of Tests, Sequence Alignment, Vaccines, DNA
Research areas
ID: 49590193