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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

Quinn, K. M., Da Costa, A., Yamamoto, A., Berry, D., Lindsay, R. W. B., Darrah, P. A., Wang, L., Cheng, C., Kong, W.-P., Gall, J. G. D., Nicosia, A., Folgori, A., Colloca, S., Cortese, R., Gostick, Emma, Price, David, Gomez, C. E., Esteban, M., Wyatt, L. S., Moss, B., Morgan, C., Roederer, M., Bailer, R. T., Nabel, G. J., Koup, R. A. and Seder, R. A. 2013. 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. The Journal of Immunology 190 (6) , pp. 2720-2735. 10.4049/jimmunol.1202861

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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 × 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+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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RM Therapeutics. Pharmacology
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 30 Jun 2017 03:34
URI: http://orca.cf.ac.uk/id/eprint/61492

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