Expanded breadth of the T-cell response to mosaic human immunodeficiency virus type 1 envelope DNA vaccination.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kong, W-P; Wu, L; Wallstrom, TC; Fischer, W; Yang, Z-Y; Ko, S-Y; Letvin, NL; Haynes, BF; Hahn, BH; Korber, B; Nabel, GJ

Published Date

  • March 2009

Published In

Volume / Issue

  • 83 / 5

Start / End Page

  • 2201 - 2215

PubMed ID

  • 19109395

Pubmed Central ID

  • 19109395

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

Digital Object Identifier (DOI)

  • 10.1128/JVI.02256-08

Language

  • eng

Conference Location

  • United States