title: HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime.
abstract: HSV-1 amplicon vectors elicit strong T-cell responses to encoded antigens but the qualitative nature of these responses is poorly understood. Antigen-specific CD4(+) and CD8(+) T-cell responses to amplicon and adenovirus (rAd5) vectors encoding HIV-1 gp120 were assessed following immunization of mice, by performing intracellular cytokine staining for IFNgamma, IL2 and TNFalpha, following stimulation of splenocytes with a HIV-1 Env peptide pool. The quality of the primary T-cell response to amplicon and rAd5 vectors was strikingly similar, but there were qualitative differences in responses to amplicon vectors that incorporated different promoters upstream of gp120 - suggesting that promoters can significantly influence immune response quality. When prime-boost combinations were studied, a rAd5 prime and amplicon boost elicited the highest T-cell response. Furthermore, protocols that incorporated a rAd5 prime consistently elicited a greater proportion of polyfunctional CD4(+) T-cells-regardless of boost. This suggests that initial priming can shape immune response quality after a boost. Overall, these findings provide insight into effective vector combinations for HIV-1 vaccine development.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Cindy M P
authors.initials: CM
authors.lastname: Duke
authors.forename: Casey A
authors.initials: CA
authors.lastname: Maguire
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
authors.forename: William J
authors.initials: WJ
authors.lastname: Bowers
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015752:Genes, env; D005822:Genetic Vectors; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D017931:DNA Primers; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120