PDF(Pubmed)
Abstract：
Shigella spp. are responsible for bacillary dysentery or shigellosis transmitted via the fecal-oral route, causing significant morbidity and mortality, especially among vulnerable populations. There are currently no licensed Shigella vaccines. Shigella spp. use a type III secretion system (T3SS) to invade host cells. We have shown that L-DBF, a recombinant fusion of the T3SS needle tip (IpaD) and translocator (IpaB) proteins with the LTA1 subunit of enterotoxigenic E. coli labile toxin, is broadly protective against Shigella spp. challenge in a mouse lethal pulmonary model. Here, we assessed the effect of LDBF, formulated with a unique TLR4 agonist called BECC470 in an oil-in-water emulsion (ME), on the murine immune response in a high-risk population (young and elderly) in response to Shigella challenge. Dual RNA Sequencing captured the transcriptome during Shigella infection in vaccinated and unvaccinated mice. Both age groups were protected by the L-DBF formulation, while younger vaccinated mice exhibited more adaptive immune response gene patterns. This preliminary study provides a step toward identifying the gene expression patterns and regulatory pathways responsible for a protective immune response against Shigella. Furthermore, this study provides a measure of the challenges that need to be addressed when immunizing an aging population.
摘要：
志贺氏菌属。负责通过粪便-口腔途径传播的细菌性痢疾或志贺氏菌病，导致显著的发病率和死亡率，特别是在弱势群体中。目前没有许可的志贺氏菌疫苗。志贺氏菌属。使用III型分泌系统（T3SS）侵入宿主细胞。我们已经证明了L-DBF，T3SS针尖（IpaD）和易位体（IpaB）蛋白与肠毒素大肠杆菌不稳定毒素的LTA1亚基的重组融合，对志贺氏菌属具有广泛的保护作用。在小鼠致死肺模型中的挑战。这里,我们评估了LDBF的效果，在水包油乳液（ME）中使用独特的TLR4激动剂BECC470配制，在高危人群（年轻人和老年人）对志贺氏菌攻击的小鼠免疫反应。双重RNA测序在接种和未接种的小鼠中志贺氏菌感染期间捕获转录组。两个年龄组都受到L-DBF制剂的保护，而年轻接种疫苗的小鼠表现出更多的适应性免疫反应基因模式。这项初步研究为鉴定负责针对志贺氏菌保护性免疫反应的基因表达模式和调节途径提供了一步。此外，这项研究提供了在对老龄人口进行免疫接种时需要应对的挑战的措施.
