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Outer Membrane Vesicles Induce Immune Responses to Virulence Proteins and Protect against Colonization by Enterotoxigenic Escherichia coli ▿

机译:外膜囊泡诱导对毒力蛋白的免疫反应,并防止肠毒素致病性大肠杆菌的定殖 ▿

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摘要

Enterotoxigenic Escherichia coli (ETEC) strains are a heterogeneous group of pathogens that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Collectively, these pathogens are responsible for hundreds of thousands of deaths annually in developing countries, particularly in children under the age of 5 years. The heterogeneity of previously investigated molecular targets and the lack of complete sustained protection afforded by antitoxin immunity have impeded progress to date toward a broadly protective vaccine. Many pathogens, including ETEC, have the capacity to form outer membrane vesicles (OMV), which often contain one or more virulence proteins. Prompted by recent studies that identified several immunogenic virulence proteins in outer membrane vesicles of ETEC, we sought to examine the immunogenicity and protective efficacy of these structures in a murine model of infection. Here we demonstrate that immunization with OMV impairs ETEC colonization of the small intestine and stimulates antibodies that recognize the heat-labile toxin and two additional putative virulence proteins, the EtpA adhesin and CexE. Similar to earlier studies with EtpA, vaccination with LT alone also inhibited intestinal colonization. Together, these findings suggest that OMV could be exploited to deliver protective antigens relevant to development of ETEC vaccines.
机译:产肠毒素的大肠杆菌(ETEC)菌株是一组异质病原体,可产生热不稳定(LT)和/或热稳定(ST)肠毒素。这些病原体共同导致发展中国家每年成千上万的死亡,特别是在5岁以下的儿童中。先前研究的分子靶标的异质性和抗毒素免疫力所提供的缺乏完整的持续保护,阻碍了迄今为止向广泛保护性疫苗的发展。许多病原体,包括ETEC,都具有形成外膜囊泡(OMV)的能力,该膜囊泡通常包含一种或多种毒力蛋白。在鉴定ETEC外膜囊泡中几种免疫原性毒力蛋白的最新研究的推动下,我们寻求在鼠类感染模型中检查这些结构的免疫原性和保护功效。在这里,我们证明了用OMV进行的免疫损害了小肠的ETEC定植,并刺激了识别热不稳定毒素和两种其他假定毒力蛋白(EtpA粘附素和CexE)的抗体。与早期的EtpA研究相似,仅用LT疫苗接种也能抑制肠道定植。总之,这些发现表明,可以利用OMV来提供与ETEC疫苗开发相关的保护性抗原。

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