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Mosaic HIV-1 Gag antigens can be processed and presented to human HIV-specific CD8+ T cells.

Abstract:
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.

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Publisher copy:
10.4049/jimmunol.1004231

Authors


Journal:
Journal of Immunology More from this journal
Volume:
186
Issue:
12
Pages:
6914-6924
Publication date:
2011-06-01
DOI:
EISSN:
1550-6606
ISSN:
0022-1767


Language:
English
Keywords:
Pubs id:
pubs:191273
UUID:
uuid:f75946d0-4bfd-4464-b79f-1bd3b9083f66
Local pid:
pubs:191273
Source identifiers:
191273
Deposit date:
2012-12-19
ARK identifier:

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