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

1
Enterotoxigenic Escherichia coli heat-stable toxin and heat-labile toxin toxoid fusion 3xSTaN12S-dmLT induces neutralizing anti-STa antibodies in subcutaneously immunized mice.产肠毒素大肠杆菌热稳定毒素和热不稳定毒素类毒素融合蛋白3xSTaN12S-dmLT在皮下免疫的小鼠中诱导产生中和抗STa抗体。
FEMS Microbiol Lett. 2016 Nov 1;363(21). doi: 10.1093/femsle/fnw246.
2
Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile toxin (LT), heat-stable toxins (STa, STb), and Shiga toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC).源自类毒素MEFA(多表位融合抗原)的抗体对猪产肠毒素大肠杆菌(ETEC)的不耐热毒素(LT)、耐热毒素(STa、STb)和志贺毒素2e(Stx2e)具有中和活性。
Vet Microbiol. 2017 Apr;202:79-89. doi: 10.1016/j.vetmic.2016.02.002. Epub 2016 Feb 6.
3
Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea.抗产肠毒素大肠杆菌相关性腹泻亚单位疫苗研发的当前进展
Clin Vaccine Immunol. 2015 Sep;22(9):983-91. doi: 10.1128/CVI.00224-15. Epub 2015 Jul 1.
4
Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity.一种CFA/I/II/IV多表位融合抗原(MEFA)与产肠毒素大肠杆菌(ETEC)的热稳定毒素(STa)和热不稳定毒素(LT)的类毒素融合体的基因融合物保留了广泛的抗CFA和抗毒素抗原性。
PLoS One. 2015 Mar 24;10(3):e0121623. doi: 10.1371/journal.pone.0121623. eCollection 2015.
5
An assessment of enterotoxigenic Escherichia coli and Shigella vaccine candidates for infants and children.婴幼儿产肠毒素大肠杆菌和志贺氏菌候选疫苗评估。
Vaccine. 2015 Feb 18;33(8):954-65. doi: 10.1016/j.vaccine.2014.11.049. Epub 2014 Dec 5.
6
Characterization of heat-stable (STa) toxoids of enterotoxigenic Escherichia coli fused to double mutant heat-labile toxin peptide in inducing neutralizing Anti-STa antibodies.研究致热稳定(STa)毒素与双突变不耐热肠毒素肽融合的肠产毒性大肠杆菌的特性,以诱导中和抗-STa 抗体。
Infect Immun. 2014 May;82(5):1823-32. doi: 10.1128/IAI.01394-13. Epub 2014 Feb 18.
7
Toxicity and immunogenicity of Enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion 3xSTa(A14Q)-LT(S63K/R192G/L211A) in a murine model.肠产毒性大肠埃希菌不耐热和耐热肠毒素融合蛋白 3xSTa(A14Q)-LT(S63K/R192G/L211A)在小鼠模型中的毒性和免疫原性。
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8
Oral immunization of a live attenuated Escherichia coli strain expressing a holotoxin-structured adhesin-toxoid fusion (1FaeG-FedF-LTA₂:5LTB) protected young pigs against enterotoxigenic E. coli (ETEC) infection.口服表达完整毒素结构黏附素-类毒素融合蛋白(1FaeG-FedF-LTA₂:5LTB)的减毒活大肠杆菌菌株可使仔猪免受肠致病性大肠杆菌(ETEC)感染。
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The Global Enteric Multicenter Study (GEMS) of diarrheal disease in infants and young children in developing countries: epidemiologic and clinical methods of the case/control study.发展中国家婴幼儿腹泻病全球肠道感染性疾病研究(GEMS):病例对照研究的流行病学和临床方法。
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10
The Global Enteric Multicenter Study (GEMS): impetus, rationale, and genesis.全球肠道疾病研究(GEMS):动力、基本原理和起源。
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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.

DOI:10.1016/j.vaccine.2016.12.021
PMID:28017433
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5261774/
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。