Immunization of cattle with a combination of purified intimin-531, EspA and Tir significantly reduces shedding of Escherichia coli O157:H7 following oral challenge

Immunization of cattle with a combination of purified intimin-531, EspA and Tir significantly reduces shedding of Escherichia coli O157:H7 following oral challenge
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DOI:
10.1016/j.vaccine.2009.10.076
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发表时间:
2010-02-03
期刊:
影响因子:
5.5
通讯作者:
Gally, David L.
Gally, David L.
中科院分区:
医学3区
文献类型:
--
作者:
McNeilly, Tom N.;Mitchell, Mairi C.;Gally, David L.

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肠出血性大肠杆菌O 157:H7是一种人体病原体,由于全身性滋贺毒素活性,可引起胃肠道疾病,并可能导致致命后果。牛是肠出血性大肠杆菌O157的主要储存宿主,需要制定干预措施,防止牛定植或限制该宿主的生物体脱落。肠出血性大肠杆菌0157主要定植于牛末端直肠,并需要III型分泌系统(T3SS)在该部位粘附和持久存在。基于含有T3S蛋白的浓缩细菌上清液的疫苗已经显示出一定的功效。在这里,我们已经证明,与T3S介导的粘附相关的抗原的组合疫苗接种,易位丝蛋白,EspA,外膜粘附素的细胞外区域,intimin,和易位的intimin受体(Tir)显着减少EHEC 0157从实验感染动物的脱落。此外,这种保护可以通过将H7鞭毛蛋白添加到先前已证明在牛中具有部分保护性的疫苗制剂中来增强。保护作用与针对确定抗原的全身和粘膜抗体应答相关,并验证了这些定殖因子的靶向作用。(C)2009爱思唯尔有限公司版权所有
Enterohemorrhagic Escherichia call (EHEC) O157:H7 is a human pathogen that can cause gastrointestinal disease with potentially fatal consequences as a result of systemic Shiga toxin activity. Cattle are the main reservoir host of EHEC O157 and interventions need to be developed that prevent cattle colonization or limit shedding of the organism from this host. EHEC 0157 predominately colonizes the bovine terminal rectum and requires a type III secretion system (T3SS) for adherence and persistence at this site. A vaccine based on concentrated bacterial supernatant that contains T3S proteins has shown some efficacy. Here we have demonstrated that vaccination with a combination of antigens associated with T3S-mediated adherence; the translocon filament protein, EspA, the extracellular region of the outer membrane adhesin, intimin, and the translocated intimin receptor (Tir) significantly reduced shedding of EHEC 0157 from experimentally infected animals. Furthermore, this protection may be augmented by addition of H7 flagellin to the vaccine preparation that has been previously demonstrated to be partially protective in cattle. Protection correlates with systemic and mucosal antibody responses to the defined antigens and validates the targeting of these colonization factors. (C) 2009 Elsevier Ltd. All rights reserved