Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells.
Polyvalent mosaic HIV immunogens offer a potential solution for generating vaccines that can elicit immune responses against genetically diverse viruses. However, it is unclear whether key T cell epitopes can be processed and presented from these synthetic Ags and recognized by epitope-specific huma...
| Автори: | , , , , , , , , |
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| Формат: | Journal article |
| Мова: | English |
| Опубліковано: |
2011
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| _version_ | 1826305589314060288 |
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| author | Ndhlovu, Z Piechocka-Trocha, A Vine, S McMullen, A Koofhethile, K Goulder, P Ndung'u, T Barouch, D Walker, B |
| author_facet | Ndhlovu, Z Piechocka-Trocha, A Vine, S McMullen, A Koofhethile, K Goulder, P Ndung'u, T Barouch, D Walker, B |
| author_sort | Ndhlovu, Z |
| collection | OXFORD |
| description | Polyvalent mosaic HIV immunogens offer a potential solution for generating vaccines that can elicit immune responses against genetically diverse viruses. However, it is unclear whether key T cell epitopes can be processed and presented from these synthetic Ags and recognized by epitope-specific human T cells. In this study, we tested the ability of mosaic HIV immunogens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors to process and present major HIV clade B and clade C CD8 T cell epitopes in human cells. A bivalent mosaic vaccine expressing HIV Gag sequences was used to transduce PBMCs from 12 HIV-1-infected individuals from the United States and 10 HIV-1-infected individuals from South Africa; intracellular cytokine staining, together with tetramer staining, was used to assess the ability of mosaic Gag Ags to stimulate pre-existing memory responses compared with natural clade B and C vectors. Mosaic Gag Ags expressed all eight clade B epitopes tested in 12 United States subjects and all 5 clade C epitopes tested in 10 South African subjects. Overall, the magnitude of cytokine production induced by stimulation with mosaic Ags was comparable to clade B and clade C Ags tested, but the mosaic Ags elicited greater cross-clade recognition. Additionally, mosaic Ags induced HIV-specific CD4 T cell responses. Our studies demonstrate that mosaic Ags express major clade B and clade C viral T cell epitopes in human cells, as well as support the evaluation of mosaic HIV-1 vaccines in humans. |
| first_indexed | 2024-03-07T06:35:07Z |
| format | Journal article |
| id | oxford-uuid:f75946d0-4bfd-4464-b79f-1bd3b9083f66 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:35:07Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:f75946d0-4bfd-4464-b79f-1bd3b9083f662022-03-27T12:42:04ZMosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f75946d0-4bfd-4464-b79f-1bd3b9083f66EnglishSymplectic Elements at Oxford2011Ndhlovu, ZPiechocka-Trocha, AVine, SMcMullen, AKoofhethile, KGoulder, PNdung'u, TBarouch, DWalker, BPolyvalent mosaic HIV immunogens offer a potential solution for generating vaccines that can elicit immune responses against genetically diverse viruses. However, it is unclear whether key T cell epitopes can be processed and presented from these synthetic Ags and recognized by epitope-specific human T cells. In this study, we tested the ability of mosaic HIV immunogens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors to process and present major HIV clade B and clade C CD8 T cell epitopes in human cells. A bivalent mosaic vaccine expressing HIV Gag sequences was used to transduce PBMCs from 12 HIV-1-infected individuals from the United States and 10 HIV-1-infected individuals from South Africa; intracellular cytokine staining, together with tetramer staining, was used to assess the ability of mosaic Gag Ags to stimulate pre-existing memory responses compared with natural clade B and C vectors. Mosaic Gag Ags expressed all eight clade B epitopes tested in 12 United States subjects and all 5 clade C epitopes tested in 10 South African subjects. Overall, the magnitude of cytokine production induced by stimulation with mosaic Ags was comparable to clade B and clade C Ags tested, but the mosaic Ags elicited greater cross-clade recognition. Additionally, mosaic Ags induced HIV-specific CD4 T cell responses. Our studies demonstrate that mosaic Ags express major clade B and clade C viral T cell epitopes in human cells, as well as support the evaluation of mosaic HIV-1 vaccines in humans. |
| spellingShingle | Ndhlovu, Z Piechocka-Trocha, A Vine, S McMullen, A Koofhethile, K Goulder, P Ndung'u, T Barouch, D Walker, B Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells. |
| title | Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells. |
| title_full | Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells. |
| title_fullStr | Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells. |
| title_full_unstemmed | Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells. |
| title_short | Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells. |
| title_sort | mosaic hiv 1 gag antigens can be processed and presented to human hiv specific cd8 t cells |
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