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I 型菌毛、CsuA/B 和 FimA 诱导针对鲍曼不动杆菌的保护性免疫应答。

Type I pili, CsuA/B and FimA induce a protective immune response against Acinetobacter baumannii.

机构信息

Department of Biology, Shahed University, Tehran Iran.

Molecular Microbiology Research Center, Shahed University, Tehran Iran; Department of Microbiology, School of Medicine, Shahed University, Tehran Iran.

出版信息

Vaccine. 2020 Jul 22;38(34):5436-5446. doi: 10.1016/j.vaccine.2020.06.052. Epub 2020 Jun 27.

Abstract

BACKGROUND

Acinetobacter baumannii, a nosocomial pathogen, is considered as a common cause of hospital and community-acquired infections. Emerging multidrug-resistance in this pathogen followed by subsequent problems in treatment has been increasing to alarming levels that warrant investigation of new therapeutic approaches. One strategy to reduce antibiotic resistance is to use of vaccines. Although there is no vaccine currently in development for this pathogen, different attempts have been made to develop one.

METHODS

In this study, we used two different recombinant pilus proteins (CsuA/B and FimA) either singly or in combination to evaluate protective efficacy against A. baumannii in lethal and sub-lethal murine sepsis models.

FINDINGS

Active immunization with recombinant proteins in combination elicited high levels of IgG antibody after the first immunization and provided 62% (five of eight mice; p < 0·001) protection against a lethal dose (1·2 × 10 CFU) of A. baumannii along with efficient clearance of bacteria in internal organs viz. spleen, liver, and lungs at sub-lethal challenge. Immunization with CsuA/B alone conferred partial protection as demonstrated by low survival rate (three [37%] of eight mice; p < 0·05) after lethal challenge and reduction of bacteria in internal organs of the mice after 24 h post-sub-lethal infection. Immunization with FimA, in comparison to CsuA/B, showed better protection (four [50%] of eight mice; p < 0·01) and reduction in CFU after 14 h.

INTERPRETATION

Our results showed that pilus proteins in combination as a single immunogen could potentially impart protection against A. baumannii.

FUNDING

Shahed University.

摘要

背景

鲍曼不动杆菌是一种医院和社区获得性感染的病原体,被认为是常见的感染源。这种病原体出现的多药耐药性以及随后的治疗问题已经增加到令人担忧的程度,需要研究新的治疗方法。减少抗生素耐药性的一种策略是使用疫苗。尽管目前没有针对这种病原体的疫苗,但已经有不同的尝试来开发一种疫苗。

方法

在这项研究中,我们使用了两种不同的重组菌毛蛋白(CsuA/B 和 FimA),单独或联合使用,以评估其在致死性和亚致死性小鼠败血症模型中对鲍曼不动杆菌的保护效果。

发现

用重组蛋白进行主动免疫,第一次免疫后可产生高水平的 IgG 抗体,并可提供 62%(8 只小鼠中的 5 只;p<0·001)的保护,免受致死剂量(1·2×10 CFU)的鲍曼不动杆菌的攻击,同时在亚致死性攻击时,内部器官(如脾、肝和肺)中的细菌也能有效清除。单独用 CsuA/B 免疫可提供部分保护,表现为在致死性攻击后存活率低(8 只小鼠中的 3 只;p<0·05),以及在亚致死性感染后 24 小时内小鼠内部器官中的细菌减少。与 CsuA/B 相比,用 FimA 免疫显示出更好的保护作用(8 只小鼠中的 4 只;p<0·01),并在 14 小时后减少 CFU。

解释

我们的结果表明,菌毛蛋白联合作为单一免疫原,可能对鲍曼不动杆菌具有潜在的保护作用。

资金

沙希德大学。

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