The present study investigates the enhancement of immunogenicity and protection efficacy of Salmonella Typhimurium ghosts surface-displayed with FliC against chicken salmonellosis. The membrane-anchored FliC is a potential TLR-5 agonist, delivers an essential adjuvant effect for the ghost vaccine candidate. The present ghost plasmid pJHL184 construct carries a convergent dual promoter system that has the temperature-dependent induction of the phage lysis gene E and the target antigen FliC at the same time. Under permissible conditions of temperatures, less than 30 °C at the presence of 20 mM l-arabinose effectively suppresses expression of the lysis gene. Once the temperature is up-lifted to 42 °C without arabinose, cause the generation of ST ghosts expelling the cytoplasmic content. The addition of FliC adjuvant significantly enhanced the IgY response, cell-mediated immune responses, regulatory cytokine induction and subsequently enhanced protection against Salmonella challenge. Further, intramuscular immunization with ST ghosts displaying FliC induced particularly high CD8+ response demarcating its proficiency to elicit Type I immune responses. Further, ST ghosts displaying FliC caused an increase in both CD4+ and CD8+ response compared to the PBS control suggesting its capability to engage both cell-mediated and humoral immune responses essential for the elimination of Salmonella. Upon the virulent challenge, we could observe a significant reduction in challenged bacterial load on spleen, liver and cecum tissues in the ST ghosts surface-displaying FliC adjuvant. Our study suggests the biological incorporation of FliC on ST ghosts enhances vaccine immunogenic potency and acts as a safe and effective prevention strategy against chicken salmonellosis.

中文翻译：

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用表面展示的大肠杆菌鞭毛蛋白对鼠伤寒沙门氏菌幽灵进行肠胃外免疫可增强TLR-5介导的免疫反应激活，从而保护鸡免受沙门氏菌感染。

本研究研究了用FliC表面展示的鼠伤寒沙门氏菌幽灵对鸡沙门氏菌病的免疫原性和保护功效。膜锚定的FliC是潜在的TLR-5激动剂，可为幽灵疫苗候选物提供基本的佐剂作用。本发明的幽灵质粒pJHL184构建体带有会聚的双启动子系统，该系统具有对噬菌体裂解基因E和靶抗原FliC的温度依赖性诱导。在允许的温度条件下，在20 mM 1-阿拉伯糖存在下低于30°C，可有效抑制裂解基因的表达。一旦温度升高至没有阿拉伯糖的42°C，将导致ST鬼魂的产生，从而消除细胞质含量。FliC佐剂的添加显着增强了IgY反应，细胞介导的免疫反应，调节性细胞因子的诱导，并随后增强了对沙门氏菌攻击的保护作用。此外，用展示FliC的ST幽灵进行肌内免疫可诱导特别高的CD8 +应答，从而区分了引起I型免疫应答的能力。此外，与PBS对照相比，展示FliC的ST幽灵引起CD4 +和CD8 +应答的增加，表明其参与消除沙门氏菌必不可少的细胞介导的和体液免疫应答的能力。进行强毒攻击后，我们可以观察到显示STli幽灵表面的FliC佐剂对脾脏，肝脏和盲肠组织的受攻击细菌负荷显着降低。