Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination

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An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I 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 -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell 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 (ICS) in inbred mice with a standardized panel of highly ... continued below

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Korber, Bette; Fischer, William & Wallstrom, Timothy January 1, 2009.

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An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I 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 -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell 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 (ICS) in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. I, 2 and 3 mosaic sets were developed that increased theoretical epitope coverage. The breadth and magnitude ofT-cell immunity stimulated by these vaccines were compared to natural strain Env's; additional comparisons were performed on mutant Env's, including gpl60 or gpl45 with or without V regions and gp41 deletions. Among them, the 2 or 3 mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the 3 mosaic set elicited responses to an average of 8 peptide pools compared to 2 pools for a set of3 natural Env's. Synthetic mosaic HIV -I 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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  • Journal Name: Journal of Virology

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  • Report No.: LA-UR-09-00148
  • Report No.: LA-UR-09-148
  • Grant Number: AC52-06NA25396
  • DOI: 10.1128/JVI.00114-09 | External Link
  • Office of Scientific & Technical Information Report Number: 956488
  • Archival Resource Key: ark:/67531/metadc926371

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Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

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  • January 1, 2009

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  • Nov. 13, 2016, 7:26 p.m.

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  • Dec. 9, 2016, 11:30 p.m.

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Korber, Bette; Fischer, William & Wallstrom, Timothy. Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination, article, January 1, 2009; [New Mexico]. (digital.library.unt.edu/ark:/67531/metadc926371/: accessed November 17, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.