E. coli Enterotoxin LtB Enhances Vaccine-Induced Anti- H. pylori Protection by Promoting Leukocyte Migration into Gastric Mucus via Inflammatory Lesions

Current studies indicate that the anti- protective efficacy of oral vaccines to a large extent depends on using mucosal adjuvants like heat-lable enterotoxin B unit (LtB). However, the mechanism by which Th17/Th1-driven cellular immunity kills and the role of LtB remains unclear. Here, two strains, expressing NapA and LtB, respectively, were orally administrated to mice. As observed, the administration of LtB significantly enhanced the fecal SIgA level and decreased gastric colonization, but also markedly aggravated gastric inflammatory injury. Both NapA group and NapA+LtB group had elevated splenocyte production of IL-8, IL-10, IL-12, IL-17, IL-23 and INF-γ. Notably, gastric leukocytes' migration or leakage into the mucus was observed more frequently in NapA+LtB group than in NapA group. This report is the first that discusses how LtB enhances vaccine-induced anti- efficacy by aggravating gastric injury and leukocytes' movement into the mucus layer. Significantly, it brings up a novel explanation for the mechanism underlying mucosal cellular immunity destroying the non-invasive pathogens. More importantly, the findings suggest the necessity to further evaluate LtB's potential hazards to humans before extending its applications. Thus, this report can provide considerable impact on the fields of mucosal immunology and vaccinology.