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从经肌肉注射免疫的类毒素融合蛋白3xSTa-dmLT获得的被动抗体可在猪模型中预防STa+产肠毒素大肠杆菌(ETEC)腹泻。

Passive antibodies derived from intramuscularly immunized toxoid fusion 3xSTa-dmLT protect against STa+ enterotoxigenic Escherichia coli (ETEC) diarrhea in a pig model.

作者信息

Nandre Rahul M, Duan Qiangde, Wang Yin, Zhang Weiping

机构信息

Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA.

Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA.

出版信息

Vaccine. 2017 Jan 23;35(4):552-556. doi: 10.1016/j.vaccine.2016.12.021. Epub 2016 Dec 22.

Abstract

Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of children's diarrhea and travelers' diarrhea. Developing effective vaccines against ETEC associated diarrhea becomes a top priority. ETEC heat-labile toxin (LT) and heat-stable toxin (STa) toxoid fusion 3xSTa-dmLT was demonstrated recently to induce neutralizing antitoxin antibodies in intraperitoneally or subcutaneously immunized mice. However, whether antibodies derived from this toxoid fusion are protective against ETEC diarrhea has not been examined. In this study, we intramuscularly immunized pregnant gilts with toxoid fusion 3xSTa-dmLT, challenged suckling piglets with a STa-positive ETEC strain, and assessed protective efficacy of passive acquire antitoxin antibodies against ETEC diarrhea. Data showed all three immunized gilts developed anti-STa IgG and IgA antibodies, and piglets born to the immunized dams acquired anti-STa and anti-LT antibodies. When challenged with a STa+ ETEC strain, none of the piglets born to the immunized dams developed watery diarrhea, with 20 piglets remained normal and the other 8 piglets developed mild diarrhea indicated with stained butt. In contrast, the control dams and born piglets had no anti-STa or anti-LT antibodies detected, and 26 out 32 piglets developed watery diarrhea after challenge of the STa+ ETEC strain. These results indicated that passive acquired anti-STa antibodies are protective against ETEC diarrhea, and suggested potential application of toxoid fusion 3xSTa-dmLT in ETEC vaccine development.

摘要

产肠毒素大肠杆菌(ETEC)菌株是儿童腹泻和旅行者腹泻最常见的病因之一。研发针对ETEC相关性腹泻的有效疫苗成为当务之急。最近有研究表明,ETEC热不稳定毒素(LT)和热稳定毒素(STa)类毒素融合物3xSTa-dmLT可在经腹腔或皮下免疫的小鼠中诱导产生中和抗毒素抗体。然而,源自这种类毒素融合物的抗体是否对ETEC腹泻具有保护作用尚未得到研究。在本研究中,我们用类毒素融合物3xSTa-dmLT对怀孕母猪进行肌肉免疫,用一株STa阳性的ETEC菌株对哺乳仔猪进行攻毒,并评估被动获得的抗毒素抗体对ETEC腹泻的保护效果。数据显示,所有三只免疫母猪均产生了抗STa IgG和IgA抗体,免疫母猪所生仔猪获得了抗STa和抗LT抗体。当用一株STa+ ETEC菌株进行攻毒时,免疫母猪所生仔猪均未出现水样腹泻,其中20只仔猪保持正常,另外8只仔猪出现轻度腹泻,表现为臀部染色。相比之下,对照母猪及其所生仔猪未检测到抗STa或抗LT抗体,32只仔猪中有26只在受到STa+ ETEC菌株攻毒后出现水样腹泻。这些结果表明,被动获得的抗STa抗体对ETEC腹泻具有保护作用,并提示类毒素融合物3xSTa-dmLT在ETEC疫苗研发中的潜在应用价值。

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