Montero David A, Del Canto Felipe, Salazar Juan C, Céspedes Sandra, Cádiz Leandro, Arenas-Salinas Mauricio, Reyes José, Oñate Ángel, Vidal Roberto M
1Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
2Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
NPJ Vaccines. 2020 Mar 12;5(1):20. doi: 10.1038/s41541-020-0168-7. eCollection 2020.
Shiga toxin-producing (STEC) cause diarrhea and dysentery, which may progress to hemolytic uremic syndrome (HUS). Vaccination has been proposed as a preventive approach against STEC infection; however, there is no vaccine for humans and those used in animals reduce but do not eliminate the intestinal colonization of STEC. The OmpT, Cah and Hes proteins are widely distributed among clinical STEC strains and are recognized by serum IgG and IgA in patients with HUS. Here, we develop a vaccine formulation based on two chimeric antigens containing epitopes of OmpT, Cah and Hes proteins against STEC strains. Intramuscular and intranasal immunization of mice with these chimeric antigens elicited systemic and local long-lasting humoral responses. However, the class of antibodies generated was dependent on the adjuvant and the route of administration. Moreover, while intramuscular immunization with the combination of the chimeric antigens conferred protection against colonization by STEC O157:H7, the intranasal conferred protection against renal damage caused by STEC O91:H21. This preclinical study supports the potential use of this formulation based on recombinant chimeric proteins as a preventive strategy against STEC infections.
产志贺毒素大肠杆菌(STEC)可引起腹泻和痢疾,病情可能进展为溶血尿毒综合征(HUS)。疫苗接种已被提议作为预防STEC感染的一种方法;然而,目前尚无用于人类的疫苗,而用于动物的疫苗虽能减少但不能消除STEC在肠道的定植。OmpT、Cah和Hes蛋白广泛分布于临床STEC菌株中,并且在HUS患者中可被血清IgG和IgA识别。在此,我们基于两种包含OmpT、Cah和Hes蛋白表位的嵌合抗原开发了一种针对STEC菌株的疫苗制剂。用这些嵌合抗原对小鼠进行肌肉注射和鼻内免疫可引发全身和局部持久的体液免疫反应。然而,所产生抗体的类别取决于佐剂和给药途径。此外,虽然用嵌合抗原组合进行肌肉注射可提供针对STEC O157:H7定植的保护作用,但鼻内免疫可提供针对STEC O91:H21所致肾损伤的保护作用。这项临床前研究支持将这种基于重组嵌合蛋白的制剂作为预防STEC感染的潜在策略。