title: Comparative analysis of the magnitude, quality, phenotype, and protective capacity of simian immunodeficiency virus gag-specific CD8+ T cells following human-, simian-, and chimpanzee-derived recombinant adenoviral vector immunization.
abstract: Recombinant adenoviral vectors (rAds) are the most potent recombinant vaccines for eliciting CD8(+) T cell-mediated immunity in humans; however, prior exposure from natural adenoviral infection can decrease such responses. In this study we show low seroreactivity in humans against simian- (sAd11, sAd16) or chimpanzee-derived (chAd3, chAd63) compared with human-derived (rAd5, rAd28, rAd35) vectors across multiple geographic regions. We then compared the magnitude, quality, phenotype, and protective capacity of CD8(+) T cell responses in mice vaccinated with rAds encoding SIV Gag. Using a dose range (1 × 10(7)-10(9) particle units), we defined a hierarchy among rAd vectors based on the magnitude and protective capacity of CD8(+) T cell responses, from most to least, as: rAd5 and chAd3, rAd28 and sAd11, chAd63, sAd16, and rAd35. Selection of rAd vector or dose could modulate the proportion and/or frequency of IFN-γ(+)TNF-α(+)IL-2(+) and KLRG1(+)CD127(-)CD8(+) T cells, but strikingly ∼30-80% of memory CD8(+) T cells coexpressed CD127 and KLRG1. To further optimize CD8(+) T cell responses, we assessed rAds as part of prime-boost regimens. Mice primed with rAds and boosted with NYVAC generated Gag-specific responses that approached ∼60% of total CD8(+) T cells at peak. Alternatively, priming with DNA or rAd28 and boosting with rAd5 or chAd3 induced robust and equivalent CD8(+) T cell responses compared with prime or boost alone. Collectively, these data provide the immunologic basis for using specific rAd vectors alone or as part of prime-boost regimens to induce CD8(+) T cells for rapid effector function or robust long-term memory, respectively.
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Kylie M
authors: KM
authors: Quinn
authors: Andreia
authors: A
authors: Da Costa
authors: Ayako
authors: A
authors: Yamamoto
authors: Dana
authors: D
authors: Berry
authors: Ross W B
authors: RW
authors: Lindsay
authors: Patricia A
authors: PA
authors: Darrah
authors: Lingshu
authors: L
authors: Wang
authors: Cheng
authors: C
authors: Cheng
authors: Wing-Pui
authors: WP
authors: Kong
authors: Jason G D
authors: JG
authors: Gall
authors: Alfredo
authors: A
authors: Nicosia
authors: Antonella
authors: A
authors: Folgori
authors: Stefano
authors: S
authors: Colloca
authors: Riccardo
authors: R
authors: Cortese
authors: Emma
authors: E
authors: Gostick
authors: David A
authors: DA
authors: Price
authors: Carmen E
authors: CE
authors: Gomez
authors: Mariano
authors: M
authors: Esteban
authors: Linda S
authors: LS
authors: Wyatt
authors: Bernard
authors: B
authors: Moss
authors: Cecilia
authors: C
authors: Morgan
authors: Mario
authors: M
authors: Roederer
authors: Robert T
authors: RT
authors: Bailer
authors: Gary J
authors: GJ
authors: Nabel
authors: Richard A
authors: RA
authors: Koup
authors: Robert A
authors: RA
authors: Seder
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D015683:Gene Products, gag / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods / Q000592:standards; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D002679:Pan troglodytes; D011785:Quality Assurance, Health Care / Q000592:standards; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D011994:Recombinant Proteins
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