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- W4313360039 abstract "Abstract ETEC are a leading cause of traveler’s diarrhea and a vaccine development priority for the US military. A subunit vaccine comprised of ETEC fimbrial tip adhesin, CfaE, adjuvanted with single-mutant heat-labile toxin, LTR192G, was given ID 3 times, 21 days apart, and evaluated for immunogenicity and efficacy against moderate to severe diarrhea (MSD) following CFA/I+ ETEC oral challenge. The homing phenotype, activation status, and cytokine production of circulating CD4+ T cells following vaccination were assessed by flow cytometry to understand the response generated by mucosal adjuvant, LT, introduced via the skin, and the potential mechanisms involved in protection from an enteric pathogen. Following in vitro stimulation with CfaE or LT 15mers, PBMCs of most vaccinated subjects expressed IFNγ or IL-17, within multiple homing subsets. Specifically, activated CfaE-specific α4β7+IFNγ+ cells were detected in 69% of vaccinated subjects, suggesting potential for gut homing, while 58% subjects generated CD62L+IFNγ+ responses. LT-specific IFNγ was observed in CD62L+ and CLA+ cells (52% and 50% subjects, respectively). Both CfaE- and LT-specific IL-17 were identified in CCR6+ (65%, 66% subjects, respectively) and CD62L+ cells (65%, 58%). Subjects without MSD following experimental challenge had significantly higher CfaE-specific activated (CD154+) α4β7+ cells (p=0.043, t-test), as well as IFNγ (p = 0.036) and IL-17 (p = 0.008) responses to vaccination. LT-specific activation of CLA+ cells (p = 0.035) and IL-17 (p = 0.032) levels were also higher in subjects without MSD. Overall, ID vaccination with CfaE and LTR192G elicited broadly homing and functional Th cell responses that may play a role in protection at the mucosal level." @default.
- W4313360039 created "2023-01-06" @default.
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- W4313360039 date "2017-05-01" @default.
- W4313360039 modified "2023-09-26" @default.
- W4313360039 title "Breadth of function and homing capacity of peripheral CD4+ Th responses to intradermal (ID) immunization with enterotoxigenic <i>E. coli</i> fimbrial tip adhesin CfaE plus adjuvant LTR192G" @default.
- W4313360039 doi "https://doi.org/10.4049/jimmunol.198.supp.73.11" @default.
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