Type-I IFN signaling is required for the induction of antigen-specific CD8+ T cell responses by adenovirus vector vaccine in the gut-mucosa

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

“…Once activated by way of an unidentified DNA sensor, STING mediates phosphorylation of IRF3 to predominantly drive IFN production (49). Signaling via TLR-and RLR-triggered pathways drives IFN production through the action of IRFs but also drives proinflammatory cyto kine production through NF-κB activation, and these pathways augment CD8 T cell immunity after rAd vaccination (16,(18)(19)(20). The relative threshold and efficiency for driving IFN production and subsequent ISG activation across STING, RLR, and TLR pathways is not known.…”

“…Additional in vitro and in vivo studies have examined early pathogen-recognition receptor (PRR) signaling and innate pathways induced after adenoviral infection or rAd exposure. In mice, deficiency of RIG-I-like receptor (RLR) or TLR adaptor proteins (mitochondrial antiviral signaling protein [MAVS], myeloid differentiation primary response gene 88 [MyD88], and TIR domain-containing adapter-inducing IFN-β [TRIF]) or individual TLRs can modestly reduce rAd-induced CD8 T cell responses (16)(17)(18)(19)(20). Adenoviral DNA also potentiates the NALP3-dependent inflammasome (21), but mice deficient in a critical component of the inflammasome generate normal CD8 T cell immunity after rAd5 vaccination (20).…”

The Early Activation ofCD8+T Cells Is Dependent on Type I IFN Signaling following Intramuscular Vaccination of Adenovirus Vector

“…Considering our previous finding that systemic Ag-specific CTLs are induced in IFNAR2 KO mice following i.m. Adv vaccination as similar as WT mice [8], it is likely that the reduction of CD69 expression on CD8 + T cells does not alter CD8 + T cell priming. For these reasons, it is suggested that type I IFN signaling-induced CD69 expression on CD8 + T cells might regulate Ag-specific CTLs in the gut mucosal compartment.…”

“…immunization with an Adv vaccine-expressing simian immunodeficiency virus (SIV) gag can induce functional and sustainable SIV gag-specific cytotoxic T lymphocytes (CTLs) in the gut mucosal compartments as well as the systemic compartments in mice and rhesus macaques [5–7]. Adv is expected to become a next generation mucosal vaccine that combats severe intracellular pathogens [8]. …”

“…We previously reported that type I IFN signaling following i.m. Adv vaccination is required for the induction of Ag-specific CTLs not in the systemic compartment but in the gut mucosal compartment [8]. Thus, type I IFN is important for the positive regulation of the Ag-specific gut mucosal cellular immune response.…”