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

Diminished Innate Antiviral Response to Adenovirus Vectors in cGAS/STING-Deficient Mice Minimally Impacts Adaptive Immunity

“…Although BMDC activation and maturation were compromised in cells derived from the cGAS Ϫ/Ϫ , STING Ϫ/Ϫ , or IRF3 Ϫ/Ϫ strain, using systemically administered virus in vivo, both vector clearance and antiviral neutralizing antibody responses occurred. The minimal impact of the type I IFN antiviral response on the adaptive immune response to AdV is consistent with data from studies characterizing antiadenovirus responses in the STAT2 knockout Syrian hamster model (64) and recent observations of rAdV vaccine vectors in IFNRI and STING knockout strains (65). Our observations that compromised dendritic cell maturation in vitro can be separated from an adaptive immune response phenotype are consistent with the characterization of the antiviral response to rAdV in type I IFN receptor knockout mice (66).…”

Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs

“…Labeling was performed using the One-Color Microarray-Based Gene Expression Analysis (v.6.5 protocol; Agilent) as described previously. 51 Microarray data for this study are available through GEO (accession number submission in process).…”

“…[37][38][39][40][41] Recent studies have used systems serology analyses to qualitatively assess antibody responses based on Fc-mediated effector functions, [42][43][44][45][46][47] which have been found to play a role in protection against simian immunodeficiency virus (SIV) 48 and HIV. 4 To assess the mechanisms by which adjuvants and vaccines mediate such effector functions, transcriptional profiling has been used in mouse models, [49][50][51][52] as well as in humans to define biomarkers to predict protection. [53][54][55] However, mouse studies are limited because the tissue distribution of TLR expression is different than humans, 56 and it is difficult to profile multiple vaccine adjuvants simultaneously in humans.…”

Beyond antigens and adjuvants: formulating future vaccines

“…The duration and magnitude of antigen and adjuvant exposure during priming of naive lymphocytes or boosting of memory cells is known to play a significant role in determining the degree of clonal expansion (109)(110)(111), fate decisions between different functional phenotypes (Th subsets or plasma cells versus memory cell differentiation of B cells; refs. 106,112), and the quality of memory established (113,114). Further, studies examining the role of temporal dosing profiles through repeated daily injections of antigen/adjuvant showed that exponentially increasing doses of an antigen and adjuvant over the course of a week could greatly increase T cell responses to a model peptide vaccine in mice (108).…”