Development of a vaccine against enterohemorrhagic Escherichia coli

肠出血性大肠杆菌(EHEC)不仅从人身上分离出来，也从牛身上分离出来。EHEC在牛和猪等牛身上的感染是一个很大的问题，而EHEC污染在人的粪便中感染。因此，开发一种针对牛EHEC感染的疫苗株可以防止EHEC感染在人类中的发生，从而防止溶血性尿毒症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。突变株构建子保留了免疫原性，但失去了对Vero细胞的细胞毒力，并在Vero毒素A亚基(Stx2e)的167位用谷氨酰胺取代谷氨酸，在170位用亮氨酸取代Ayine，产生了转基因毒素。由于亲本野生株对猪有致病性，而突变株对猪没有致病作用，因此将突变株命名为YT106，以检测其对水肿病的保护性免疫。接种TY106疫苗的20头猪全部存活，但20头未接种疫苗的猪中，只有8头在用野生菌株挑战后存活。此外，与对照组相比，8头存活的猪的增重率有所下降。血液免疫球蛋白和肠道免疫球蛋白A滴度分别提高了3.3倍和1.6倍，表明YT106有可能成为预防水肿病的减毒活疫苗株。

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.