Development of a vaccine against enterohemorrhagic Escherichia coli

肠出血性大肠杆菌（EHEC）不仅从人身上分离，也从牛身上分离。EHEC在牛、猪等家畜中的感染是一个很大的问题，人感染EHEC的粪便中也有EHEC的污染。因此，研制出一株抗牛EHEC感染的疫苗株，可以预防人EHEC感染，从而预防溶血性尿毒综合征等并发症的发生。开发的疫苗株的有效性也得到了证明。构建了一株保留免疫原性但丧失Vero细胞毒性的突变株，并通过Vero毒素A亚基的167位谷氨酸与170位亮氨酸与赖氨酸的互补作用产生了遗传修饰毒素（Stx2e）。由于亲本野生株对猪有致病性，而突变株对猪无致病性，因此将命名为YT 106的突变株给予猪以检测其对水肿病的保护性免疫。所有20头TY106免疫猪均存活，但在用野生毒株攻毒后，20头未免疫猪中仅8头存活。此外，8只存活猪的增重率相对于对照组有所下降。血液IgG和肠道伊加滴度分别增加了3.3和1.6倍，比对照组，表明YT 106可能是一个很好的候选人的减毒活疫苗株，以防止水肿病。

Enterohemorrhagic Escherichia coli(EHEC) is isolated from not only humans but also from cattle. EHEC infection in cattle such as cows and pigs is a big prolem and EHEC contaminated in feces of human infection. Thus a development of a vaccine strain against EHEC infection in cattle may prevent the occurrence of EHEC infection in human, and therefore prevent a complication such as hemolytic uremic syndrome.In this study we developed a vaccine strain of EHEC that causes porcine edema disease. Effectiveness of the developed vaccine strain was also demonstrated. A mutant strain constructer retained immunogenicity but lost Vero cell cytotoxicy, and produced genetically modified toxin by replaciy glutamate with glutamine at position 167 and ayine with leucine at position 170 of the A subunit of Vero toxin (Stx2e). As the parent wild strain was pathogenic to pigs but the mutant strain was not, the mutant strain named as YT106 was given to the pigs to examine its protective immunity against edema disease. All 20 pigs vaccinated with TY106 survived but only 8 of 20 nonvaccinated pigs survived after the challenge with a wild strain. Also, the 8 survived pigs had decreased rates of gain relative to those of the controls. Blood IgG and intestinal IgA titers increased 3.3 and 1.6 times, respectively, more then the control, showing that YT106 might be a good candidate of a live-attenuated vaccine strain to protect against edema disease.