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Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling

Quinn, Kylie M., Zak, Daniel E., Costa, Andreia, Yamamoto, Ayako, Kastenmuller, Kathrin, Hill, Brenna J., Lynn, Geoffrey M., Darrah, Patricia A., Lindsay, Ross W.B., Wang, Lingshu, Cheng, Cheng, Nicosia, Alfredo, Folgori, Antonella, Colloca, Stefano, Cortese, Riccardo, Gostick, Emma, Price, David, Gall, Jason G.D., Roederer, Mario, Aderem, Alan and Seder, Robert A. 2015. Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling. The Journal of Clinical Investigation 125 (3) , pp. 1129-1146. 10.1172/JCI78280

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Abstract

Recombinant adenoviral vectors (rAds) are lead vaccine candidates for protection against a variety of pathogens, including Ebola, HIV, tuberculosis, and malaria, due to their ability to potently induce T cell immunity in humans. However, the ability to induce protective cellular immunity varies among rAds. Here, we assessed the mechanisms that control the potency of CD8 T cell responses in murine models following vaccination with human-, chimpanzee-, and simian-derived rAds encoding SIV-Gag antigen (Ag). After rAd vaccination, we quantified Ag expression and performed expression profiling of innate immune response genes in the draining lymph node. Human-derived rAd5 and chimpanzee-derived chAd3 were the most potent rAds and induced high and persistent Ag expression with low innate gene activation, while less potent rAds induced less Ag expression and robustly induced innate immunity genes that were primarily associated with IFN signaling. Abrogation of type I IFN or stimulator of IFN genes (STING) signaling increased Ag expression and accelerated CD8 T cell response kinetics but did not alter memory responses or protection. These findings reveal that the magnitude of rAd-induced memory CD8 T cell immune responses correlates with Ag expression but is independent of IFN and STING and provide criteria for optimizing protective CD8 T cell immunity with rAd vaccines.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RM Therapeutics. Pharmacology
Additional Information: Publisher PDF allowed on institutional repository according to http://www.sherpa.ac.uk/romeo/issn/0021-9738/ [accessed 10/03/2016]
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 23 December 2014
Last Modified: 03 Aug 2017 14:04
URI: http://orca.cf.ac.uk/id/eprint/87673

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