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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

2013; American Association of Immunologists; Volume: 190; Issue: 6 Linguagem: Inglês

10.4049/jimmunol.1202861

1550-6606

Kylie M. Quinn, Andréia da Silva Costa, Ayako Yamamoto, Dana Berry, Ross Lindsay, Patricia A. Darrah, Lingshu Wang, Cheng Cheng, Wing-Pui Kong, Jason G. Gall, Alfredo Nicosia, Antonella Folgori, Stefano Colloca, Riccardo Cortese, Emma Gostick, David A. Price, Carmen Gómez, Mariano Estéban, Linda S. Wyatt, Bernard Moss, Cecilia Morgan, Mario Roederer, Robert T. Bailer, Gary J. Nabel, Richard A. Koup, Robert A. Seder,

CAR-T cell therapy research

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.