Bowser Sarah, Melton-Celsa Angela, Chapartegui-González Itziar, Torres Alfredo G
Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Vaccines (Basel). 2024 May 8;12(5):508. doi: 10.3390/vaccines12050508.
Enterohemorrhagic (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 , 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 while AuNP-EscC successfully limited infection with non-Stx2d-producing . 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 described here, could be the key to finally developing an effective EHEC vaccine that can progress into human clinical trials.
肠出血性大肠杆菌(EHEC)是一类致病细菌,与全球范围内的人类食源性腹泻疾病以及溶血尿毒综合征的发生有关,溶血尿毒综合征是一种与志贺毒素(Stxs)相关的潜在致命疾病。目前,尚无获批用于人类预防感染的疫苗,而阻碍成功研发EHEC疫苗的一个障碍是缺乏可靠的动物模型,包括小鼠,小鼠对EHEC感染具有天然抗性,不会表现出该疾病的特征性症状。我们实验室之前开发了基于金纳米颗粒(AuNP)的EHEC疫苗,并使用EHEC的小鼠病原体对应物以及一种产生Stx2d的菌株评估了它们的功效,该菌株在小鼠中会导致更一致的疾病动力学,包括致死率。本研究的目的是继续评估这些疫苗以增强保护作用。在此,我们证明,用与EHEC抗原EscC和紧密黏附素(Eae)连接的AuNP对小鼠进行皮下免疫,单独或同时进行,均可引发强大的功能性全身体液反应。此外,同时用两种抗原进行疫苗接种对产生Stx2d的菌株显示出一定疗效,而AuNP-EscC成功限制了非产生Stx2d菌株的感染。总体而言,收集到的结果表明,我们的AuNP疫苗在预防EHEC疾病方面具有广阔的潜力,并且使用此处描述的合适动物模型评估新型疫苗可能是最终开发出一种能够进入人体临床试验的有效EHEC疫苗的关键。