title: Expanded breadth of the T-cell response to mosaic human immunodeficiency virus type 1 envelope DNA vaccination.
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.
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, Maryland 20892-3005, USA.
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.forename: Lan
authors.initials: L
authors.lastname: Wu
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wallstrom
authors.forename: Will
authors.initials: W
authors.lastname: Fischer
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: Sung-Youl
authors.initials: SY
authors.lastname: Ko
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D051379:Mice; D015233:Models, Statistical; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D019444:Vaccines, DNA / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus