Identification of novel vaccine candidates against Acinetobacter baumannii using reverse vaccinology
Identification of novel vaccine candidates against Acinetobacter baumannii using reverse vaccinology
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DOI：
10.1080/21645515.2015.1010910
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发表时间：
2015-04-03
影响因子：
4.8
通讯作者：
Chong, Pele
中科院分区：
文献类型：
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作者：
Chiang, Ming-Hsien;Sung, Wang-Chou;Chong, Pele
鲍曼不动杆菌（Acinetobacter baumannii，Ab）是一种全球性的新型细菌，可引起医院感染，如肺炎、脑膜炎、菌血症和软组织感染，尤其是重症监护病房。由于抗体对几乎所有常规抗生素都有耐药性，它现在是美国传染病学会列出的6种危险微生物之一。疫苗的开发是预防感染的最有前途和最具成本效益的策略之一。在这项研究中，我们使用反向疫苗学鉴定了潜在的保护性候选疫苗。我们分析了14个在线可获得的Ab基因组序列，发现2752个同源核心基因。使用从免疫蛋白质组学实验中获得的信息，发表的蛋白质组学信息和生物信息学PSORTb v3.0软件来预测细胞外和/或外膜蛋白的位置，鉴定并选择77个基因进行进一步研究。在排除那些已被PubMed和Google Scholar的计算机搜索引擎报告用作疫苗候选物的抗原之后，13种蛋白质可能是潜在的疫苗候选物。我们选择并克隆了3个抗原基因，并进一步表达和纯化。发现这些抗原具有高度免疫原性，并在肺炎动物模型中提供部分保护（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点，并且易于执行以鉴定用于多组分疫苗开发的新型免疫原。
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.