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首页> 外文期刊>Vaccine >An improved vaccine for prevention of respiratory tularemia caused by Francisella tularensis SchuS4 strain.
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An improved vaccine for prevention of respiratory tularemia caused by Francisella tularensis SchuS4 strain.

机译：一种改进的疫苗，用于预防由土拉弗朗西斯菌SchuS4菌株引起的呼吸道Tularemia。

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Vaccination of mice with Francisella tularensis live vaccine strain (LVS) mutants described so far have failed to induce protection in C57BL/6 mice against challenge with the virulent strain F. tularensis SchuS4. We have previously reported that a mutant of F. tularensis LVS deficient in iron superoxide dismutase (sodB(Ft)) is hypersensitive to oxidative stress and attenuated for virulence in mice. Herein, we evaluated the efficacy of this mutant as a vaccine candidate against respiratory tularemia caused by F. tularensis SchuS4. C57BL/6 mice were vaccinated intranasally (i.n.) with the sodB(Ft) mutant and challenged i.n. with lethal doses of F. tularensis SchuS4. The level of protection against SchuS4 challenge was higher in sodB(Ft) vaccinated group as compared to the LVS vaccinated mice. sodB(Ft) vaccinated mice following SchuS4 challenge exhibited significantly reduced bacterial burden in lungs, liver and spleen, regulated production of pro-inflammatory cytokines and less severe histopathological lesions compared to the LVS vaccinated mice. The sodB(Ft) vaccination induced a potent humoral immune response and protection against SchuS4 required both CD4 and CD8 T cells in the vaccinated mice. sodB(Ft) mutants revealed upregulated levels of chaperonine proteins DnaK, GroEL and Bfr that have been shown to be important for generation of a potent immune response against Francisella infection. Collectively, this study describes an improved live vaccine candidate against respiratory tularemia that has an attenuated virulence and enhanced protective efficacy than the LVS.
机译：到目前为止描述的土拉弗朗西斯菌活疫苗株（LVS）突变体的小鼠疫苗接种未能诱导C57BL / 6小鼠抵抗强毒株Tularensis SchuS4的攻击。以前我们已经报道过，缺乏铁超氧化物歧化酶（sodB（Ft））的土拉弗朗西斯LVS突变体对氧化应激高度敏感，并且对小鼠的毒力减弱。本文中，我们评估了该突变体作为候选疫苗的功效，该疫苗候选疫苗是针对由T.ularularensis SchuS4引起的呼吸道Tularemia的。 C57BL / 6小鼠鼻内（i.n.）接种了sodB（Ft）突变体并进行了i.n攻击。用致命剂量的F. tularensis SchuS4。与LVS疫苗接种的小鼠相比，在sodB（Ft）疫苗接种的组中，针对SchuS4攻击的保护水平更高。与LVS疫苗接种的小鼠相比，经SchuS4攻击的sodB（Ft）疫苗接种的小鼠表现出显着降低的肺，肝和脾脏细菌负担，调节的促炎性细胞因子生成以及较不严重的组织病理学病变。 sodB（Ft）疫苗诱导了有效的体液免疫应答，并且针对SchuS4的保护需要接种小鼠中的CD4和CD8 T细胞。 sodB（Ft）突变体揭示了伴侣蛋白DnaK，GroEL和Bfr的上调水平，这些蛋白对于产生针对弗朗西斯菌感染的有效免疫反应非常重要。总体而言，这项研究描述了一种改良的抗呼吸道疾病的活疫苗候选物，与LVS相比，其毒力减弱且保护功效增强。

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