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Immunogenicity of Pasteurella multocida and Mannheimia haemolytica outer membrane vesicles

机译:多杀巴斯德氏菌和溶血曼海姆氏菌外膜囊泡的免疫原性

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Pasteurella multocida is able to cause disease in humans and in a wide range of animal hosts, including fowl cholera in birds, atrophic rhinitis in pigs, and snuffles in rabbits. Together with Mannheimia haemolytica, P. multocida also represents a major bacterial causative agent of bovine respiratory disease (BRD), which is one of the most important causes for economic losses for the cattle backgrounding and feedlot industry. Commercially available vaccines only partially prevent infections caused by P. multocida and M. haemolytica. Thus, this study characterized the immunogenicity of P. multocida and M. haemolytica outer membrane vesicles (OMVs) upon intranasal immunization of BALB/c mice. Enzyme-linked immunosorbent assays (ELISA) revealed that OMVs derived from P. multocida or M. haemolytica are able to induce robust humoral and mucosal immune responses against the respective donor strain. In addition, also significant cross-immunogenic potential was observed for both OMV types. Colonization studies showed that a potential protective immune response against P. multocida is not only achieved by immunization with P. multocida OMVs, but also by immunization with OMVs derived from M. haemolytica. Immunoblot and immunoprecipitation analyses demonstrated that M. haemolytica OMVs induce a more complex immune response compared to P. multocida OMVs. The outer membrane proteins OmpA, OmpH, and P6 were identified as the three major immunogenic proteins of P. multocida OMVs. Amongst others, the serotype 1-specific antigen, an uncharacterized outer membrane protein, as well as the outer membrane proteins P2 and OmpA were found to be the most important antigens of M. haemolytica OMVs. These findings are useful for the future development of broad-spectrum OMV based vaccines against BRD and other infections caused by P. multocida or M. haemolytica.
机译:多杀性巴斯德氏菌能够在人类和多种动物宿主中引起疾病​​,包括鸟类的禽霍乱,猪的萎缩性鼻炎和兔子的鼻涕。疟原虫与溶血性曼氏菌一起也代表了牛呼吸道疾病(BRD)的主要细菌病原,这是造成牛饲养和饲养场经济损失的最重要原因之一。市售疫苗仅能部分预防由多杀性疟原虫和溶血支原体引起的感染。因此,这项研究的特点是在鼻腔内对BALB / c小鼠进行免疫后,多杀性疟原虫和溶血支原体外膜囊泡(OMV)具有免疫原性。酶联免疫吸附试验(ELISA)表明,衍生自多杀疟原虫或溶血支原体的OMV能够诱导针对各个供体菌株的强健的体液和粘膜免疫反应。另外,对于两种OMV类型也观察到显着的交叉免疫原性潜力。殖民化研究表明,不仅可以通过用多杀疟原虫OMV免疫,而且还可以通过使用溶血支原体衍生的OMV免疫来实现针对多杀疟原虫的潜在保护性免疫应答。免疫印迹和免疫沉淀分析表明溶血支原体OMV与多杀疟原虫OMV相比诱导了更复杂的免疫反应。外膜蛋白OmpA,OmpH和P6被鉴定为多杀性疟原虫OMV的三种主要免疫原性蛋白。其中,血清型1特异性抗原,未表征的外膜蛋白以及外膜蛋白P2和OmpA被发现是溶血支原体OMV的最重要抗原。这些发现对于基于广谱OMV的针对BRD和多杀疟原虫或溶血支原体引起的其他感染的疫苗的未来开发很有用。

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