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Yersinia enterocolitica ghost with msbB mutation provides protection and reduces proinflammatory cytokines in mice.

机译:带有msbB突变的小肠结肠炎耶尔森菌幽灵可提供保护并减少小鼠的促炎细胞因子。

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Yersinia enterocolitica is an important human pathogen. Yersiniosis, caused by Y. enterocolitica, has become more prevalent globally in recent years. Prevention of yersiniosis still remains a challenge, and an efficacious and safe vaccine that confers protection against this enteric pathogen needs to be developed. In this study, a novel vaccine based on the bacterial ghost, in combination with mutation of the Y. enterocolitica msbB gene, was developed and the immunopotency of this vaccine was evaluated in mice. Significant levels of IgG1/IgG2a antibodies and IL-4/IFN- gamma cytokines were detected after mice were administered this vaccine intragastrically, indicating that a Th1/Th2-mediated mixed immune response was stimulated. Importantly, mutation of the msbB gene efficiently reduced secretion of the proinflammatory cytokines IL-1 beta , IL-6 and TNF- alpha , suggesting a reduction in inflammatory reaction caused by lipopolysaccharide. In addition, when challenged with a dose that was 100-fold the minimal lethal dose of the virulent wild strain of Y. enterocolitica, this mutated ghost vaccine was capable of eliciting the same effective protection (80%) in comparison with the non-mutated ghost strain, and the survival time was extended by at least two days. Together, our results demonstrated that this novel ghost bacterial strain could be used as a safe and effective vaccine against Y. enterocolitica.
机译:小肠结肠炎耶尔森菌是一种重要的人类病原体。近年来,由小肠结肠炎耶尔森菌引起的耶尔森病在全球范围内变得越来越普遍。预防耶尔森氏菌病仍然是一个挑战,需要开发一种有效且安全的疫苗以赋予针对这种肠道病原体的保护。在这项研究中,开发了一种新的疫苗,该疫苗基于细菌的幽灵,并结合了小肠结肠炎耶尔森氏菌msbB基因的突变,并在小鼠中评估了该疫苗的免疫力。在小鼠胃内给予该疫苗后,检测到IgG1 / IgG2a抗体和IL-4 /IFN-γ细胞因子的显着水平,表明刺激了Th1 / Th2介导的混合免疫反应。重要的是,msbB基因的突变有效地减少了促炎细胞因子IL-1β,IL-6和TNF-α的分泌,表明由脂多糖引起的炎症反应减少。另外,当以最小剂量的致命致死性小肠结肠炎耶尔森氏菌的100倍剂量进行攻击时,这种突变的幽灵疫苗与未突变的幽灵疫苗相比能够引起相同的有效保护(80%)鬼应变,生存时间至少延长了两天。在一起,我们的结果表明,这种新型幽灵细菌菌株可以用作抗小肠结肠炎耶尔森氏菌的安全有效疫苗。

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