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

Korber, Bette; Fischer, William; Wallstrom, Timothy

doi:10.1128/JVI.00114-09

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

Journal Article · Thu Jan 01 00:00:00 EST 2009 · Journal of Virology

DOI:https://doi.org/10.1128/JVI.00114-09· OSTI ID:956488

Korber, Bette ^[1]; Fischer, William ^[1]; Wallstrom, Timothy ^[1]

Los Alamos National Laboratory

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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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC52-06NA25396

OSTI ID:: 956488

Report Number(s):: LA-UR-09-00148; LA-UR-09-148; JOVIAM; TRN: US201013%%191

Journal Information:: Journal of Virology, Journal Name: Journal of Virology; ISSN 0022-538X

Country of Publication:: United States

Language:: English

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

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