Optimizing the Protection of Cattle against Escherichia coli O157:H7 Colonization through Immunization with Different Combinations of H7 Flagellin, Tir, Intimin-531 or EspA.
Optimizing the Protection of Cattle against Escherichia coli O157:H7 Colonization through Immunization with Different Combinations of H7 Flagellin, Tir, Intimin-531 or EspA.
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DOI：
10.1371/journal.pone.0128391
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gally DL
中科院分区：
文献类型：
--
作者：
McNeilly TN;Mitchell MC;Corbishley A;Nath M;Simmonds H;McAteer SP;Mahajan A;Low JC;Smith DG;Huntley JF;Gally DL
肠出血性大肠杆菌（EHEC）是重要的人类病原体，可引起人类出血性结肠炎和溶血性尿毒综合征。大肠杆菌O157:H7是全世界与肠出血性大肠杆菌感染相关的最常见血清型，尽管其他非O157血清型也会导致危及生命的感染。牛是肠出血性大肠杆菌的主要宿主，旨在限制牛肠出血性大肠杆菌排泄的干预策略预计将降低人类感染的风险。我们之前已经证明，用重组型EHEC O157:H7的III型分泌系统（T3SS）相关蛋白EspA、内膜素和Tir免疫犊牛可显著减少实验定植犊牛的EHEC O157脱落，并且可以通过在疫苗制剂中添加H7鞭毛蛋白来增强这种保护作用。本研究的主要目的是通过确定这些抗原的关键组合来优化我们目前的肠出血性大肠杆菌O157亚单位疫苗配方。第二个目的是确定疫苗诱导的抗体反应是否与其他肠出血性大肠杆菌血清型抗原具有交叉反应潜力。用EspA、内膜素和Tir免疫可减少攻毒后肠出血性大肠杆菌O157的平均脱落量，但不能减少犊牛的平均定植比例。与所有其他组相比，去除Tir会导致更长时间的脱落，而用H7鞭毛蛋白代替Tir会产生最高水平的保护，无论是在减少肠出血性大肠杆菌O157的平均脱落和定植小牛的比例方面。用重组EHEC O157 EspA、内膜素和Tir免疫犊牛可产生能够与非O157 EHEC血清型抗原发生交叉反应的抗体，这表明用这些抗原免疫犊牛可能对其他EHEC血清型提供一定程度的交叉保护。现在需要进一步的研究来测试这些疫苗在实地的效力，并正式测试疫苗对其他非o157型肠出血性大肠杆菌的交叉保护潜力。
Enterohemorrhagic Escherichia coli (EHEC) are important human pathogens, causing hemorrhagic colitis and hemolytic uraemic syndrome in humans. E. coli O157:H7 is the most common serotype associated with EHEC infections worldwide, although other non-O157 serotypes cause life-threatening infections. Cattle are a main reservoir of EHEC and intervention strategies aimed at limiting EHEC excretion from cattle are predicted to lower the risk of human infection. We have previously shown that immunization of calves with recombinant versions of the type III secretion system (T3SS)-associated proteins EspA, intimin and Tir from EHEC O157:H7 significantly reduced shedding of EHEC O157 from experimentally-colonized calves, and that protection could be augmented by the addition of H7 flagellin to the vaccine formulation. The main aim of the present study was to optimize our current EHEC O157 subunit vaccine formulations by identifying the key combinations of these antigens required for protection. A secondary aim was to determine if vaccine-induced antibody responses exhibited cross-reactive potential with antigens from other EHEC serotypes. Immunization with EspA, intimin and Tir resulted in a reduction in mean EHEC O157 shedding following challenge, but not the mean proportion of calves colonized. Removal of Tir resulted in more prolonged shedding compared with all other groups, whereas replacement of Tir with H7 flagellin resulted in the highest levels of protection, both in terms of reducing both mean EHEC O157 shedding and the proportion of colonized calves. Immunization of calves with recombinant EHEC O157 EspA, intimin and Tir resulted in the generation of antibodies capable of cross-reacting with antigens from non-O157 EHEC serotypes, suggesting that immunization with these antigens may provide a degree of cross-protection against other EHEC serotypes. Further studies are now required to test the efficacy of these vaccines in the field, and to formally test the cross-protective potential of the vaccines against other non-O157 EHEC.
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影响因子：
3.4
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