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Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling
Kylie M. Quinn, … , Alan Aderem, Robert A. Seder
Kylie M. Quinn, … , Alan Aderem, Robert A. Seder
Published February 2, 2015
Citation Information: J Clin Invest. 2015;125(3):1129-1146. https://doi.org/10.1172/JCI78280.
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Research Article Article has an altmetric score of 61

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

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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.

Authors

Kylie M. Quinn, Daniel E. Zak, Andreia Costa, Ayako Yamamoto, Kathrin Kastenmuller, Brenna J. Hill, Geoffrey M. Lynn, Patricia A. Darrah, Ross W.B. Lindsay, Lingshu Wang, Cheng Cheng, Alfredo Nicosia, Antonella Folgori, Stefano Colloca, Riccardo Cortese, Emma Gostick, David A. Price, Jason G.D. Gall, Mario Roederer, Alan Aderem, Robert A. Seder

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Figure 9

Correlation of Ag expression with innate gene expression.

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Correlation of Ag expression with innate gene expression.
(A) Heat map r...
(A) Heat map representation of genes from module C2 and C3 that exhibit differential regulation at 24 hours that is significantly negatively associated with Ag expression at 72 hours after rAd vaccination in the dLNs. Colors indicate scaled fold changes (magenta, upregulated; white, no change; cyan, downregulated) for the mean – SEM, mean, and mean ± SEM response compared with the average response in mice vaccinated with PBS control. (B) Scatter plots of negative correlations between Ag expression at 72 hours and module C2 or genes derived from C2, such as Eif2ak2, and with module C3 or genes derived from C3, such as Ifna1, with gene expression assessed at 24 hours. (C) Scatter plots of positive correlations between Ag expression at 72 hours and NK-related gene expression (Klra7 and Klrd1) at 24 hours. Red shading bounded by black lines represents 99% confidence intervals (from stratified bootstrap resampling of spline fits between innate gene expression and Ag), colored lines in x and y planes are SEM for each vaccine group (for genes or Ag), and shading in gray scale represents the scatter plot for combining all possible innate data with all possible Ag data for each vector.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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