OmpW is a potential target for eliciting protective immunity against Acinetobacter baumannii infections

OmpW is a potential target for eliciting protective immunity against Acinetobacter baumannii infections
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DOI:
10.1016/j.vaccine.2015.07.031
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发表时间:
2015-08-26
期刊:
影响因子:
5.5
通讯作者:
Ma, Yanbing
Ma, Yanbing
中科院分区:
医学3区
文献类型:
--
作者:
Huang, Weiwei;Wang, Shijie;Ma, Yanbing

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鲍曼不动杆菌(A.baumannii,A.baumannii)是引起医院感染和社区感染的重要条件致病菌。在这项研究中,我们试图探讨外膜蛋白W(OmpW)是否是诱导对鲍曼不动杆菌感染的保护性免疫的潜在靶点。用硫氧还蛋白-OmpW融合蛋白免疫的小鼠产生了强的OmpW特异性免疫球蛋白抗体。在脓毒症模型中,针对OmpW的主动和被动免疫都有效地保护小鼠免受鲍曼不动杆菌的感染。这种保护作用表现为显著提高了存活率,减少了器官内的细菌负荷,并抑制了血清中炎性细胞因子和趋化因子的积累。小鼠巨噬细胞RAW264.7细胞吞噬光声试验表明,免疫小鼠抗血清的杀菌作用是由特异性抗体和补体成分协同介导的。在体外,抗血清对同源菌株和克隆性不同的临床分离株表现出显著的吞噬细胞活性。蛋白质数据分析表明,报道的鲍曼不动杆菌OmpW基因序列具有91%以上的保守性,其分子长度为183个氨基酸。总之,我们认为OmpW是一种高度免疫原性和保守性的蛋白,对于开发有效的疫苗或制备抗血清来控制鲍曼不动杆菌感染是一个有价值的抗原候选。(C)2015爱思唯尔有限公司。保留所有权利。
Acinetobacter baumannii (A. baumannii) is an important conditioned pathogen that causes nosocomial and community-associated infections. In this study, we sought to investigate whether outer membrane protein W (OmpW) is a potential target for eliciting protective immunity against A. baumannii infections. Mice immunized with the fusion protein thioredoxin-OmpW generated strong OmpW-specific IgG responses. In a sepsis model, both active and passive immunizations against OmpW effectively protected mice from A. baumannii infections. This protection was demonstrated by a significantly improved survival rate, reduced bacterial burdens within organs, and the suppressed accumulation of inflammatory cytokines and chemokines in sera. Opsonophagocytic assays with murine macrophage RAW264.7 cells indicated that the bactericidal effects of the antisera derived from the immunized mice are mediated synergistically by specific antibodies and complement components. The antisera presented significant opsonophagocytic activities against homologous strains and clonally distinct clinical isolates in vitro. Protein data analysis showed that the sequence of OmpW, which has a molecule length of 183 amino acids, is more than 91% conserved in reported A. baumannii strains. In conclusion, we identified OmpW as a highly immunogenic and conserved protein as a valuable antigen candidate for the development of an effective vaccine or the preparation of antisera to control A. baumannii infections. (C) 2015 Elsevier Ltd. All rights reserved.