Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines.
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 univers...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1826288432188489728 |
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| author | Karlsson, I Kløverpris, H Jensen, K Stryhn, A Buus, S Karlsson, A Vinner, L Goulder, P Fomsgaard, A |
| author_facet | Karlsson, I Kløverpris, H Jensen, K Stryhn, A Buus, S Karlsson, A Vinner, L Goulder, P Fomsgaard, A |
| author_sort | Karlsson, I |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:13:36Z |
| format | Journal article |
| id | oxford-uuid:a179d066-163d-48f1-ab9b-17d70d9b7910 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:13:36Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:a179d066-163d-48f1-ab9b-17d70d9b79102022-03-27T02:13:27ZIdentification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a179d066-163d-48f1-ab9b-17d70d9b7910EnglishSymplectic Elements at Oxford2012Karlsson, IKløverpris, HJensen, KStryhn, ABuus, SKarlsson, AVinner, LGoulder, PFomsgaard, AThe 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. |
| spellingShingle | Karlsson, I Kløverpris, H Jensen, K Stryhn, A Buus, S Karlsson, A Vinner, L Goulder, P Fomsgaard, A Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. |
| title | Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. |
| title_full | Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. |
| title_fullStr | Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. |
| title_full_unstemmed | Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. |
| title_short | Identification of conserved subdominant HIV Type 1 CD8(+) T Cell epitopes restricted within common HLA Supertypes for therapeutic HIV Type 1 vaccines. |
| title_sort | 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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