TY - JOUR
T1 - 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
AU - Quinn, Kylie M.
AU - Da Costa, Andreia
AU - Yamamoto, Ayako
AU - Berry, Dana
AU - Lindsay, Ross W B
AU - Darrah, Patricia A.
AU - Wang, Lingshu
AU - Cheng, Cheng
AU - Kong, Wing Pui
AU - Gall, Jason G D
AU - Nicosia, Alfredo
AU - Folgori, Antonella
AU - Colloca, Stefano
AU - Cortese, Riccardo
AU - Gostick, Emma
AU - Price, David A.
AU - Gomez, Carmen E.
AU - Esteban, Mariano
AU - Wyatt, Linda S.
AU - Moss, Bernard
AU - Morgan, Cecilia
AU - Roederer, Mario
AU - Bailer, Robert T.
AU - Nabel, Gary J.
AU - Koup, Richard A.
AU - Seder, Robert A.
PY - 2013/3/15
Y1 - 2013/3/15
N2 - 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 3 107-109 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+;CD1272CD8 +; 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.
AB - 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 3 107-109 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+;CD1272CD8 +; 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.
UR - http://www.scopus.com/inward/record.url?scp=84874860188&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1202861
DO - 10.4049/jimmunol.1202861
M3 - Article
C2 - 23390298
AN - SCOPUS:84874860188
VL - 190
SP - 2720
EP - 2735
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -