Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination
Identifieur interne : 002932 ( Main/Curation ); précédent : 002931; suivant : 002933Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination
Auteurs : Wing-Pui Kong [États-Unis] ; LAN WU [États-Unis] ; Timothy C. Wallstrom [États-Unis] ; Will Fischer [États-Unis] ; Zhi-Yong Yang [États-Unis] ; Sung-Youl Ko [États-Unis] ; Norman L. Letvin [États-Unis] ; Barton F. Haynes [États-Unis] ; Beatrice H. Hahn [États-Unis] ; Bette Korber [États-Unis] ; Gary J. Nabel [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2009.
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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.
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination</title>
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<author><name sortKey="Korber, Bette" sort="Korber, Bette" uniqKey="Korber B" first="Bette" last="Korber">Bette Korber</name>
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<author><name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J." last="Nabel">Gary J. Nabel</name>
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<series><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AIDS</term>
<term>Cellular immunity</term>
<term>Genetic vaccine</term>
<term>HIV-1 virus</term>
<term>Virology</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Virus HIV1</term>
<term>Immunité cellulaire</term>
<term>Vaccin génétique</term>
<term>Virologie</term>
<term>SIDA</term>
</keywords>
</textClass>
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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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