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

Wing Pui Kong, Lan Wu, Timothy C. Wallstrom, Will Fischer, Zhi Yong Yang, Sung Youl Ko, Norman L. Letvin, Barton F. Haynes, Beatrice H. Hahn, Bette Korber, Gary J. Nabel

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2201-2215
Number of pages15
JournalJournal of Virology
Volume83
Issue number5
DOIs
StatePublished - Mar 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology

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  • Cite this

    Kong, W. P., Wu, L., Wallstrom, T. C., Fischer, W., Yang, Z. Y., Ko, S. Y., Letvin, N. L., Haynes, B. F., Hahn, B. H., Korber, B., & Nabel, G. J. (2009). Expanded breadth of the T-cell response to mosaic human immunodeficiency virus type 1 envelope DNA vaccination. Journal of Virology, 83(5), 2201-2215. https://doi.org/10.1128/JVI.02256-08