title: Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling.
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
authors: KM
authors: Quinn
authors: Daniel E
authors: DE
authors: Zak
authors: Andreia
authors: A
authors: Costa
authors: Ayako
authors: A
authors: Yamamoto
authors: Kathrin
authors: K
authors: Kastenmuller
authors: Brenna J
authors: BJ
authors: Hill
authors: Geoffrey M
authors: GM
authors: Lynn
authors: Patricia A
authors: PA
authors: Darrah
authors: Ross W B
authors: RW
authors: Lindsay
authors: Lingshu
authors: L
authors: Wang
authors: Cheng
authors: C
authors: Cheng
authors: Alfredo
authors: A
authors: Nicosia
authors: Antonella
authors: A
authors: Folgori
authors: Stefano
authors: S
authors: Colloca
authors: Riccardo
authors: R
authors: Cortese
authors: Emma
authors: E
authors: Gostick
authors: David A
authors: DA
authors: Price
authors: Jason G D
authors: JG
authors: Gall
authors: Mario
authors: M
authors: Roederer
authors: Alan
authors: A
authors: Aderem
authors: Robert A
authors: RA
authors: Seder
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000096:biosynthesis* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology; D015683:Gene Products, gag / Q000096:biosynthesis*; D007113:Immunity, Innate / Q000235:genetics; D007372:Interferons / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D015533:Transcriptional Activation; D059467:Transcriptome; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology; D000099197:STING Protein
chemical_list: D000956:Antigens, Viral; D015683:Gene Products, gag; D007372:Interferons; D008565:Membrane Proteins; D051192:Receptors, Pattern Recognition; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C530855:Sting1 protein, mouse; D000099197:STING Protein
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