Shigella spp. cause bacillary dysentery (shigellosis) with high morbidity and mortality in low- and middle-income countries. Infection occurs through the fecal-oral route and can be devastating for vulnerable populations, including infants and the elderly. These bacteria invade host cells using a type III secretion system (T3SS). No licensed vaccine yet exists for shigellosis, but we have generated a recombinant fusion protein, L-DBF, combining the T3SS needle tip protein (IpaD), translocator protein (IpaB), and the LTA1 subunit of enterotoxigenic E. coli labile toxin, which offers broad protection in a mouse model of lethal pulmonary infection. The L-DBF vaccine protects high-risk groups, including young and elderly mice. Here, we investigated how the gut microbiota of young and elderly mice responds to intranasal L-DBF vaccination formulated in an oil-in-water emulsion (ME). Samples from lungs, small intestines, and feces were collected on day 14 after 2 or 3 doses of L-DBF in ME. 16S rRNA gene sequencing revealed age-dependent changes in gut microbiota post-vaccination. The vaccine-induced changes were more prominent in the elderly mice and were most significant in the intestinal tract, indicating that vaccination by the intranasal route can have a tremendous impact on the gut environment. These findings provide insight into the communication between the intranasal mucosal surface following subunit vaccination and the microbiota at a distant mucosal site, thereby highlighting the impact of vaccination and the host's microbiome.

中文翻译：

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鼻内 L-DBF 疫苗对年轻和老年小鼠肠道微生物群的影响。


志贺菌属可引起细菌性痢疾（志贺菌病），在低收入和中等收入国家/地区发病率和死亡率很高。感染通过粪口途径发生，对包括婴儿和老年人在内的弱势群体可能是毁灭性的。这些细菌使用 III 型分泌系统 （T3SS） 侵入宿主细胞。目前还没有针对志贺菌病的许可疫苗，但我们已经生成了一种重组融合蛋白 L-DBF，结合了 T3SS 针尖蛋白 （IpaD）、转运蛋白 （IpaB） 和产肠毒素大肠杆菌不稳定毒素的 LTA1 亚基，它在致命肺部感染的小鼠模型中提供了广泛的保护。L-DBF 疫苗可保护高危人群，包括年轻和老年小鼠。在这里，我们研究了年轻和老年小鼠的肠道微生物群对水包油乳剂 （ME） 中配制的鼻内 L-DBF 疫苗接种的反应。在 ME 中接受 2 或 3 剂 L-DBF 后，第 14 天收集来自肺、小肠和粪便的样本。16S rRNA 基因测序揭示了接种疫苗后肠道微生物群的年龄依赖性变化。疫苗诱导的变化在老年小鼠中更为明显，在肠道中最为显着，表明鼻内途径接种疫苗可对肠道环境产生巨大影响。这些发现提供了对亚单位疫苗接种后鼻内粘膜表面与远处粘膜部位微生物群之间交流的见解，从而突出了疫苗接种和宿主微生物组的影响。