Immunization with H7-HCP-tir-intimin significantly reduces colonization and shedding of Escherichia coli O157:H7 in goats.
Immunization with H7-HCP-tir-intimin significantly reduces colonization and shedding of Escherichia coli O157:H7 in goats.
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H7-HCP-Tir-Intimin 免疫可显着减少山羊体内大肠杆菌 O157:H7 的定植和脱落
DOI：
10.1371/journal.pone.0091632
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
He K
中科院分区：
文献类型：
--
作者：
Zhang X;Yu Z;Zhang S;He K
肠出血性大肠杆菌（EHEC）O 157：H7是人类出血性结肠炎和溶血性尿毒综合征的病原体。然而，这种细菌可以在反刍动物的肠道中定植，而不会引起临床症状。肠出血性大肠杆菌O 157：H7需要鞭毛（H7）和出血性大肠杆菌皮利（HCP）粘附于上皮细胞。然后，细菌使用易位的内膜受体（Tir）和外膜粘附（Intimin）蛋白来定殖宿主。这导致（A/E）病变的附着和消失。构建了由H7、HCP、Tir和Intimin蛋白的免疫学重要部分组成的四价重组疫苗（H7-HCP-Tir-Intimin），并使用山羊模型评价其效力。结果表明，重组疫苗能诱导机体产生较强的体液和粘膜免疫应答，并能保护机体免受EHEC O 157：H7 86-24株的活菌攻击。第二次免疫后，平均IgG滴度达到7.2×105。攻毒后5天，E.大肠杆菌O 157：H7在接种疫苗的山羊粪便中不再检测到，但未接种疫苗的山羊在整个攻毒过程中都会脱落细菌。肠组织培养结果表明，H7-HCP-Tir-Intimin免疫山羊可有效降低肠出血性大肠杆菌O 157：H7的肠道定植量。重组H7-HCP-Tir-Intimin蛋白是一种很好的疫苗候选物。本研究的数据保证了进一步的有效性研究，旨在减少EHEC O 157：H7在农场的负荷和这种人畜共患病原体对尸体的污染。
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is the causative agent of hemorrhagic colitis and hemolytic uremic syndrome in humans. However, the bacterium can colonize the intestines of ruminants without causing clinical signs. EHEC O157:H7 needs flagella (H7) and hemorrhagic coli pili (HCP) to adhere to epithelial cells. Then the bacterium uses the translocated intimin receptor (Tir) and an outer membrane adhesion (Intimin) protein to colonize hosts. This leads to the attachment and effacement of (A/E) lesions. A tetravalent recombinant vaccine (H7-HCP-Tir-Intimin) composed of immunologically important portions of H7, HCP, Tir and Intimin proteins was constructed and its efficacy was evaluated using a caprine model. The results showed that the recombinant vaccine induced strong humoral and mucosal immune responses and protected the subjects from live challenges with EHEC O157:H7 86-24 stain. After a second immunization, the average IgG titer peaked at 7.2×105. Five days after challenge, E. coli O157:H7 was no longer detectable in the feces of vaccinated goats, but naïve goats shed the bacterium throughout the course of the challenge. Cultures of intestinal tissues showed that vaccination of goats with H7-HCP-Tir-Intimin reduced the amount of intestinal colonization by EHEC O157:H7 effectively. Recombinant H7-HCP-Tir-Intimin protein is an excellent vaccine candidate. Data from the present study warrant further efficacy studies aimed at reducing EHEC O157:H7 load on farms and the contamination of carcasses by this zoonotic pathogen.
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