Comparative analysis of the magnitude, quality, phenotype, and protective capacity of simian immunodeficiency virus gag-specific CD8+ T cells following human …

KM Quinn, A Da Costa, A Yamamoto… - The Journal of …, 2013 - journals.aai.org
KM Quinn, A Da Costa, A Yamamoto, D Berry, RWB Lindsay, PA Darrah, L Wang, C Cheng
The Journal of Immunology, 2013journals.aai.org
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 …
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.
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