肠出血性大肠杆菌(EHEC)是一组与全球人类食源性腹泻疾病和溶血性尿毒综合征的发展有关的致病菌,与志贺毒素(Stxs)相关的潜在致命疾病。目前,已批准的预防人类感染的疫苗不存在,阻碍EHEC疫苗成功生产的一个障碍是缺乏可靠的动物模型,包括老鼠,对EHEC感染具有天然抗性,并且不表现出疾病的特征性体征。我们的实验室先前开发了基于金纳米粒子(AuNP)的EHEC疫苗,并使用柠檬酸杆菌属评估其疗效,这是EHEC的小鼠病原体对应物,以及产生Stx2d的菌株,在小鼠中导致更一致的疾病动力学,包括杀伤力。这项研究的目的是继续评估这些疫苗以增加保护作用。这里,我们证明了用与EHEC抗原EscC和内膜蛋白(Eae)相关的AuNPs对小鼠进行皮下免疫,单独或同时,引起功能性强健的系统体液反应。此外,两种抗原一起接种对产生Stx2d的C.rodentium显示出一定的功效,而AuNP-EscC成功地限制了非产生Stx2d的C.rodentium的感染。总的来说,收集的结果表明,我们的AuNP疫苗具有预防EHEC疾病的潜力,以及使用适当的动物模型评估新型疫苗,就像这里描述的C.rodentium,可能是最终开发出可以进入人体临床试验的有效EHEC疫苗的关键。
Enterohemorrhagic E. coli (
EHEC) is a group of pathogenic bacteria that is associated with worldwide human foodborne diarrheal illnesses and the development of hemolytic uremic syndrome, a potentially deadly condition associated with Shiga toxins (Stxs). Currently, approved vaccines for human prophylaxis against infection do not exist, and one barrier preventing the successful creation of
EHEC vaccines is the absence of dependable animal models, including mice, which are naturally resistant to
EHEC infection and do not manifest the characteristic signs of the illness. Our lab previously developed gold nanoparticle (AuNP)-based
EHEC vaccines, and assessed their efficacy using Citrobacter rodentium, which is the mouse pathogen counterpart of EHEC, along with an Stx2d-producing strain that leads to more consistent disease kinetics in mice, including lethality. The purpose of this study was to continue evaluating these vaccines to increase protection. Here, we demonstrated that subcutaneous immunization of mice with AuNPs linked to the
EHEC antigens EscC and intimin (Eae), either alone or simultaneously, elicits functional robust systemic humoral responses. Additionally, vaccination with both antigens together showed some efficacy against Stx2d-producing C. rodentium while AuNP-EscC successfully limited infection with non-Stx2d-producing C. rodentium. Overall, the collected results indicate that our AuNP vaccines have promising potential for preventing disease with EHEC, and that evaluation of novel vaccines using an appropriate animal model, like C. rodentium described here, could be the key to finally developing an effective EHEC vaccine that can progress into human clinical trials.