Non-typhoidal Salmonella enterica (NTS) is a major global foodborne pathogen that poses a major public health concern worldwide, and no vaccines are available for protecting against infection of multiple Salmonella serotypes, therefore, the development of Salmonella vaccines to provide broad protection is valuable. In this work, we aimed to regulate lipopolysaccharide (LPS) synthesis of live Salmonella in vivo for exposing conserved protein antigens on the outer membrane while maintaining smooth LPS patterns in vitro to keep their original ability to invade host cells for inducing cross-protection against infection of multiple Salmonella serotypes. We generated a series of mutants defective in genes to affect the length of LPS. These mutants exhibit in vivo regulated-delayed attenuation and altered length of LPS, and all these mutants were derived from SW067 (ΔpagL7 ΔpagP81::Plpp lpxE ΔlpxR9 Δfur9) containing ∆pagP81::Plpp lpxE mutation to reduce their endotoxic activity. Animal experiments demonstrated that all regulated delayed attenuated mutants exhibited reduced ability to colonize the organs of the mice, and SW114 (waaI), SW116 (waaJ), SW118 (waaL), and SW120 (wbaP) induced a significant production of IgG and IgA against OMPs isolated from S. Typhimurium, S. Enteritidis, and S. Choleraesuis. SW114 (waaI), SW116 (waaJ), and SW118 (waaL) were capable of conferring significant protection against infection of wild-type S. Enteritidis and S. Choleraesuis, with SW118 (waaL) triggering significant CD4+ T-cell responses as well as the B220low IgG+ BM cell. In conclusion, regulated delayed attenuated Salmonella vaccines with the whole core oligosaccharides of LPS showed a goo.d ability to expose conserved outer antigens and to trigger strong cross-immune responses against both homologous and heterologous Salmonella infections. These results give new insight into the development of the Salmonella vaccine against multiple serotypes of Salmonella.

中文翻译：

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具有调节脂多糖长度的延迟减毒沙门氏菌诱导的小鼠免疫原性和交叉保护功效。


非伤寒肠道沙门氏菌 （NTS） 是一种主要的全球食源性病原体，在世界范围内构成重大公共卫生问题，目前尚无疫苗可用于预防多种沙门氏菌血清型感染，因此，开发沙门氏菌疫苗以提供广泛的保护是有价值的。在这项工作中，我们旨在调节体内活沙门氏菌的脂多糖 （LPS） 合成，以暴露外膜上保守的蛋白质抗原，同时在体外保持光滑的 LPS 模式，以保持它们最初侵入宿主细胞的能力，以诱导对多种沙门氏菌血清型感染的交叉保护。我们生成了一系列基因缺陷的突变体，以影响 LPS 的长度。这些突变体在体内表现出调节的延迟衰减和 LPS 长度的改变，所有这些突变体都来源于含有 ∆pagP81：:P lpp lpxE 突变的 SW067 （ΔpagL7 ΔpagP81：:P lpp lpxE ΔlpxR9 Δfur9），以降低其内毒活性。动物实验表明，所有受调节的延迟减毒突变体在小鼠器官中定植的能力降低，SW114 （waaI）、SW116 （waaJ）、SW118 （waaL） 和 SW120 （wbaP） 诱导了针对从鼠伤寒沙门氏菌、肠炎沙门氏菌和霍乱沙门氏菌中分离的 OMP 的 IgG 和 IgA 的显着产生。SW114 （waaI） 、SW116 （waaJ） 和 SW118 （waaL） 能够对野生型肠炎链球菌和霍乱链球菌的感染提供显着保护，其中 SW118 （waaL） 触发显着的 CD4+ T 细胞反应以及 B220low IgG+ BM 细胞。总之，具有 LPS 整个核心寡糖的受监管延迟减毒沙门氏菌疫苗显示出粘液。d 能够暴露保守的外部抗原并触发针对同源和异源沙门氏菌感染的强烈交叉免疫反应。这些结果为针对多种血清型沙门氏菌的沙门氏菌疫苗的开发提供了新的见解。