Expanded breadth of the T-cell response to mosaic human immunodeficiency virus type 1 envelope DNA vaccination.
Identifieur interne : 002795 ( Main/Exploration ); précédent : 002794; suivant : 002796Expanded breadth of the T-cell response to mosaic human immunodeficiency virus type 1 envelope DNA vaccination.
Auteurs : Wing-Pui Kong [États-Unis] ; Lan Wu ; Timothy C. Wallstrom ; Will Fischer ; Zhi-Yong Yang ; Sung-Youl Ko ; Norman L. Letvin ; Barton F. Haynes ; Beatrice H. Hahn ; Bette Korber ; Gary J. NabelSource :
- Journal of virology [ 1098-5514 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Déterminants antigéniques des lymphocytes T (immunologie), Femelle, Immunité cellulaire, Lymphocytes T (immunologie), Lymphocytes T (virologie), Modèles statistiques, Produits du gène env du virus de l'immunodéficience humaine (immunologie), Souris, VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie), Vaccins contre le SIDA (immunologie), Vaccins à ADN (immunologie).
- MESH :
- immunologie : Déterminants antigéniques des lymphocytes T, Lymphocytes T, Produits du gène env du virus de l'immunodéficience humaine, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Vaccins contre le SIDA, Vaccins à ADN.
- virologie : Lymphocytes T.
- Animaux, Femelle, Immunité cellulaire, Modèles statistiques, Souris.
English descriptors
- KwdEn :
- MESH :
- chemical , immunology : AIDS Vaccines, Epitopes, T-Lymphocyte, Vaccines, DNA, env Gene Products, Human Immunodeficiency Virus.
- immunology : HIV-1, T-Lymphocytes.
- virology : T-Lymphocytes.
- Animals, Female, Immunity, Cellular, Mice, Models, Statistical.
Abstract
An effective AIDS vaccine must control highly diverse circulating strains of human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV-1 Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential T-cell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. One-, two-, and three-mosaic sets that increased theoretical epitope coverage were developed. The breadth and magnitude of T-cell immunity stimulated by these vaccines were compared to those for natural strain Envs; additional comparisons were performed on mutant Envs, including gp160 or gp145 with or without V regions and gp41 deletions. Among them, the two- or three-mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the three-mosaic set elicited responses to an average of eight peptide pools, compared to two pools for a set of three natural Envs. Synthetic mosaic HIV-1 antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T-cell-based HIV-1 vaccines.
DOI: 10.1128/JVI.02256-08
PubMed: 19109395
Affiliations:
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Le document en format XML
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<term>Immunity, Cellular</term>
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<front><div type="abstract" xml:lang="en">An effective AIDS vaccine must control highly diverse circulating strains of human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV-1 Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential T-cell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. One-, two-, and three-mosaic sets that increased theoretical epitope coverage were developed. The breadth and magnitude of T-cell immunity stimulated by these vaccines were compared to those for natural strain Envs; additional comparisons were performed on mutant Envs, including gp160 or gp145 with or without V regions and gp41 deletions. Among them, the two- or three-mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the three-mosaic set elicited responses to an average of eight peptide pools, compared to two pools for a set of three natural Envs. Synthetic mosaic HIV-1 antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T-cell-based HIV-1 vaccines.</div>
</front>
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