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一种靶向铜绿假单胞菌毒力因子的嵌合疫苗可保护小鼠免受致命感染。

A chimeric vaccine targeting Pseudomonas aeruginosa virulence factors protects mice against lethal infection.

作者信息

Korpi Fatemeh, Irajian Gholamreza, Forouhi Fatemeh, Mohammadian Taher

机构信息

Department of Cell and Molecular Biology, Faculty of Basic Science, Islamic Azad University Shahre Qods Branch, Iran.

Department of Cell and Molecular Biology, Faculty of Basic Science, Islamic Azad University Shahre Qods Branch, Iran; Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Microb Pathog. 2023 May;178:106033. doi: 10.1016/j.micpath.2023.106033. Epub 2023 Feb 20.

Abstract

Pseudomonas aeruginosa is an important and hazardous nosocomial pathogen in respiratory tract infections and rapidly achieves antibiotic resistance, so it is necessary to develop an effective vaccine to combat the infection. The Type III secretion system (T3SS) protein P. aeruginosa V-antigen (PcrV), outer membrane protein F (OprF), and two kinds of flagellins (FlaA and FlaB) all play important roles in the pathogenesis of P. aeruginosa lung infection and its spread into deeper tissues. In a mouse acute pneumonia model, the protective effects of a chimer vaccine including PcrV, FlaA, FlaB, and OprF (PABF) protein were investigated. PABF immunization prompted robust opsonophagocytic titer of IgG antibodies and decreased bacterial burden, and improved survival afterward intranasal challenge with ten times 50% lethal doses (LD50) of P. aeruginosa strains, indicating its broad-spectrum immunity. Moreover, these findings showed a promise chimeric vaccine candidate to treat and control P. aeruginosa infections.

摘要

铜绿假单胞菌是呼吸道感染中一种重要且危险的医院病原体,并且能迅速产生抗生素耐药性,因此有必要研发一种有效的疫苗来对抗这种感染。Ⅲ型分泌系统(T3SS)蛋白铜绿假单胞菌V抗原(PcrV)、外膜蛋白F(OprF)以及两种鞭毛蛋白(FlaA和FlaB)在铜绿假单胞菌肺部感染的发病机制及其扩散至更深组织的过程中均发挥着重要作用。在小鼠急性肺炎模型中,研究了一种包含PcrV、FlaA、FlaB和OprF(PABF)蛋白的嵌合疫苗的保护作用。PABF免疫可促使IgG抗体产生强大的调理吞噬滴度,降低细菌载量,并在经10倍50%致死剂量(LD50)的铜绿假单胞菌菌株进行鼻内攻击后提高生存率,表明其具有广谱免疫性。此外,这些研究结果显示出一种有望用于治疗和控制铜绿假单胞菌感染的嵌合疫苗候选物。

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