Protection against Shiga toxin-producing Escherichia coli infection by transcutaneous immunization with Shiga toxin subunit B.

Protection against Shiga toxin-producing Escherichia coli infection by transcutaneous immunization with Shiga toxin subunit B.
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通过志贺毒素 B 亚基经皮免疫预防产生志贺毒素的大肠杆菌感染。

DOI:
10.1128/cvi.00399-07
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发表时间:
2008
期刊:
Clinical and vaccine immunology : CVI
影响因子:
--
通讯作者:
Boedeker,EC
Boedeker,EC
中科院分区:
--
文献类型:
--
作者:
Zhu,C;Yu,J;Yang,Z;Davis,K;Rios,H;Wang,B;Glenn,G;Boedeker,EC

文献摘要

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大肠埃希菌(EHEC)是人类重要的食源性致病菌。肠出血性大肠杆菌菌株产生强效滋贺毒素(Stx 1和/或Stx 2),与出血性结肠炎(HC)或溶血性尿毒症综合征(HUS)的发生有关。在这份报告中,我们评估了Stx 1亚单位B(StxB 1)的免疫原性和保护效果,通过经皮免疫(TCI)。三组荷兰皮带兔接受含有StxB 1、StxB 1与大肠杆菌不耐热肠毒素(LT)联合或单独LT的贴剂。另一组未处理的家兔作为对照组。用StxB 1 TCI后的保护效力通过用Stx 1产毒菌株RDEC-H19 A攻击兔子来评估,RDEC-H19 A能够在兔子中诱导HC和HUS。采用酶联免疫吸附试验和毒素中和试验检测血清和胆汁中StxB 1的特异性抗体。用StxB 1免疫的兔表现出改善的体重增加和减少Stx诱导的组织病理学。接受StxB或StxB 1/LT的家兔显示StxB 1特异性血清免疫球蛋白G滴度以及毒素中和滴度显著增加。这些数据表明,通过TCI递送的StxB可以诱导显著的全身免疫应答。因此,Stx亚单位B疫苗通过用于高危人群的贴片递送可能是预防(和/或减少)Stx诱导的病理的实用方法。
EnterohemorrhagicEscherichia coli(EHEC) strains are important human food-borne pathogens. EHEC strains elaborate potent Shiga toxins (Stx1, and/or Stx2) implicated in the development of hemorrhagic colitis (HC) or hemolytic-uremic syndrome (HUS). In this report, we evaluated the immunogenicity and protective efficacy of Stx1 subunit B (StxB1) administered by transcutaneous immunization (TCI). Three groups of Dutch Belted rabbits received patches containing StxB1, StxB1 in combination withEscherichia coliheat-labile enterotoxin (LT), or LT alone. An additional group of naïve rabbits served as controls. The protective efficacy following TCI with StxB1 was assessed by challenging rabbits with a virulent Stx1-producing strain, RDEC-H19A, capable of inducing HC and HUS in rabbits. Antibodies specific to StxB1 from serum and bile samples were determined by enzyme-linked immunosorbent assay and toxin neutralization test. Rabbits immunized with StxB1 demonstrated improved weight gain and reduced Stx-induced histopathology. Rabbits receiving StxB or StxB1/LT showed a significant increase in serum immunoglobulin G titers specific to StxB1 as well as toxin neutralization titers. These data demonstrated that the StxB delivered by TCI could induce significant systemic immune responses. Thus, Stx subunit B vaccine delivered by a patch for a high-risk population may be a practical approach to prevent (and/or reduce) Stx-induced pathology.