Asper David J, Sekirov Inna, Finlay B Brett, Rogan Dragan, Potter Andrew A
Vaccine & Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3.
Vaccine. 2007 Nov 28;25(49):8262-9. doi: 10.1016/j.vaccine.2007.09.054. Epub 2007 Oct 12.
Escherichia coli O157:H7 is an important food- and water-borne pathogen of humans, causing Hemorrhagic Colitis and Haemolytic Uremic Syndrome. Colonization of both cattle and human hosts is mediated through the action of effector molecules secreted via a Type III secretion system, a mechanism shared by other enterohemorrhagic E. coli (EHEC). We recently reported that vaccination of cattle with Type III-secreted proteins (TTSPs) resulted in decreased shedding of the organism following both experimental infection as well as under conditions of natural exposure. In order to extend this to non-O157 EHEC serotypes, we examined the serological cross reactivity of TTSPs of serotypes O26:H11, O103:H2, O111:NM and O157:H7. Western blotting experiments with polyclonal antisera directed against serotype O157:H7 TTSPs suggested that there was significant cross reactivity, although there was limited cross reactivity when two Tir- and EspA-specific monoclonal antibodies were used. Groups of cattle were then vaccinated with TTSPs produced from each of the above serotypes and the magnitude and specificity of the responses were measured. All animals responded well with antibodies to TTSPs of the homologous serotype. However, limited cross reactivity was observed against the others. No cross reactivity was observed against Tir and EspA of serotype O157:H7. These results suggest that vaccination of cattle with TTSPs as a means of reducing the risk of EHEC transmission to humans will induce protection that is serotype specific.
大肠杆菌O157:H7是一种重要的通过食物和水传播的人类病原体,可引起出血性结肠炎和溶血性尿毒综合征。牛和人类宿主的定殖是通过III型分泌系统分泌的效应分子介导的,这是其他肠出血性大肠杆菌(EHEC)共有的一种机制。我们最近报道,用III型分泌蛋白(TTSPs)对牛进行疫苗接种,在实验感染以及自然暴露条件下,均可导致该生物体的排出量减少。为了将此扩展到非O157 EHEC血清型,我们检测了O26:H11、O103:H2、O111:NM和O157:H7血清型TTSPs的血清学交叉反应性。用针对O157:H7血清型TTSPs的多克隆抗血清进行的蛋白质印迹实验表明存在显著的交叉反应性,尽管使用两种Tir和EspA特异性单克隆抗体时交叉反应性有限。然后用上述每种血清型产生的TTSPs对牛群进行疫苗接种,并测量反应的强度和特异性。所有动物对同源血清型的TTSPs抗体反应良好。然而,对其他血清型观察到有限的交叉反应性。未观察到对O157:H7血清型的Tir和EspA的交叉反应性。这些结果表明,用TTSPs对牛进行疫苗接种作为降低EHEC传播给人类风险的一种手段,将诱导血清型特异性的保护作用。