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.
Korber, Bette, et al. "Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination." Journal of Virology, Dec. 2008. https://doi.org/10.1128/JVI.00114-09
Korber, Bette, Fischer, William, & Wallstrom, Timothy (2008). Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination. Journal of Virology. https://doi.org/10.1128/JVI.00114-09
Korber, Bette, Fischer, William, and Wallstrom, Timothy, "Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination," Journal of Virology (2008), https://doi.org/10.1128/JVI.00114-09
@article{osti_956488,
author = {Korber, Bette and Fischer, William and Wallstrom, Timothy},
title = {Expanded breadth of the T-cell response to mosaic HIV-1 envelope DNA vaccination},
annote = {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.},
doi = {10.1128/JVI.00114-09},
url = {https://www.osti.gov/biblio/956488},
journal = {Journal of Virology},
issn = {ISSN 0022-538X},
place = {United States},
year = {2008},
month = {12}}