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利用反向疫苗学鉴定针对鲍曼不动杆菌的新型疫苗候选物。

Identification of novel vaccine candidates against Acinetobacter baumannii using reverse vaccinology.

作者信息

Chiang Ming-Hsien, Sung Wang-Chou, Lien Shu-Pei, Chen Ying-Zih, Lo Annie Fei-yun, Huang Jui-Hsin, Kuo Shu-Chen, Chong Pele

机构信息

a Vaccine R&D Center; National Institute of Infectious Diseases and Vaccinology ; National Health Research Institutes ; Zhunan Town , Taiwan.

出版信息

Hum Vaccin Immunother. 2015;11(4):1065-73. doi: 10.1080/21645515.2015.1010910.

Abstract

Acinetobacter baumannii (Ab) is a global emerging bacterium causing nosocomial infections such as pneumonia, meningitis, bacteremia and soft tissue infections especially in intensive care units. Since Ab is resistant to almost all conventional antibiotics, it is now one of the 6 top-priorities of the dangerous microorganisms listed by the Infectious Disease Society of America. The development of vaccine is one of the most promising and cost-effective strategies to prevent infections. In this study, we identified potential protective vaccine candidates using reverse vaccinology. We have analyzed 14 on-line available Ab genome sequences and found 2752 homologous core genes. Using information obtained from immuno-proteomic experiments, published proteomic information and the bioinformatics PSORTb v3.0 software to predict the location of extracellular and/or outer membrane proteins, 77 genes were identified and selected for further studies. After excluding those antigens have been used as vaccine candidates reported by the in silico search-engines of PubMed and Google Scholar, 13 proteins could potentially be vaccine candidates. We have selected and cloned the genes of 3 antigens that were further expressed and purified. These antigens were found to be highly immunogenic and conferred partial protection (60%) in a pneumonia animal model. The strategy described in the present study incorporates the advantages of reverse vaccinology, bioinformatics and immuno-proteomic platform technologies and is easy to perform to identify novel immunogens for multi-component vaccines development.

摘要

鲍曼不动杆菌(Ab)是一种全球范围内新出现的细菌,可引发医院感染,如肺炎、脑膜炎、菌血症和软组织感染,尤其是在重症监护病房。由于鲍曼不动杆菌对几乎所有传统抗生素均具有耐药性,它现已成为美国传染病协会列出的6种最优先关注的危险微生物之一。开发疫苗是预防感染最具前景且成本效益高的策略之一。在本研究中,我们使用反向疫苗学方法鉴定了潜在的保护性疫苗候选物。我们分析了14个在线可得的鲍曼不动杆菌基因组序列,发现了2752个同源核心基因。利用免疫蛋白质组学实验获得的信息、已发表的蛋白质组学信息以及生物信息学软件PSORTb v3.0来预测细胞外和/或外膜蛋白的位置,鉴定并选择了77个基因进行进一步研究。在排除那些已被PubMed和谷歌学术搜索引擎报道为疫苗候选物的抗原后,有13种蛋白质可能成为疫苗候选物。我们选择并克隆了3种抗原的基因,对其进行进一步表达和纯化。这些抗原被发现具有高度免疫原性,并在肺炎动物模型中提供了部分保护(60%)。本研究中描述的策略结合了反向疫苗学、生物信息学和免疫蛋白质组学平台技术的优势,易于实施以鉴定用于开发多组分疫苗的新型免疫原。

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