Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Academia Nacional de Medicina, Buenos Aires, Argentina.
Laboratorio de Fisiología de Procesos Inflamatorios, IMEX CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
Front Cell Infect Microbiol. 2023 May 16;13:1143918. doi: 10.3389/fcimb.2023.1143918. eCollection 2023.
Shiga-toxin (Stx) producing (STEC) O157:H7 is the most frequent serotype associated with hemolytic uremic syndrome (HUS) after gastrointestinal infections. Protection against HUS secondary to STEC infections has been experimentally assayed through the generation of different vaccine formulations. With focus on patients, the strategies have been mainly oriented to inhibit production of Stx or its neutralization. However, few approaches have been intended to block gastrointestinal phase of this disease, which is considered the first step in the pathogenic cascade of HUS. The aim of this work was to assay H7 flagellin as a mucosal vaccine candidate to prevent the systemic complications secondary to O157:H7 infections.
The cellular and humoral immune response after H7 nasal immunization in mice were studied by the analysis of systemic and intestinal specific antibody production, as well as cytokine production and lymphocyte proliferation against H7 flagellin ex vivo.
Immunized mice developed a strong and specific anti-H7 IgG and IgA response, at systemic and mucosal level, as well as a cellular Th1/Th2/Th17 response. H7 induced activation of bone marrow derived dendritic cells and a significant delayed-type hypersensitivity (DTH) response in immunized mice. Most relevant, immunized mice were completely protected against the challenge with an O157:H7 virulent strain , and surviving mice presented high titres of anti-H7 and Stx antibodies.
These results suggest that immunization avoids HUS outcome and allows to elicit a specific immune response against other virulence factors.
产志贺毒素（Stx）的 （STEC）O157：H7 是胃肠道感染后与溶血性尿毒症综合征（HUS）相关的最常见血清型。通过生成不同的疫苗配方，已经在实验中检测了针对 STEC 感染的 HUS 保护作用。以患者为重点，这些策略主要集中在抑制 Stx 的产生或中和上。然而，很少有方法旨在阻止这种疾病的胃肠道阶段，这被认为是 HUS 发病级联的第一步。本工作旨在研究 H7 鞭毛蛋白作为一种黏膜疫苗候选物，以预防 O157：H7 感染引起的全身并发症。
通过分析系统和肠道特异性抗体的产生以及针对 H7 鞭毛蛋白的细胞因子产生和淋巴细胞增殖，研究了 H7 鼻内免疫后小鼠的细胞和体液免疫反应。
免疫小鼠在系统和黏膜水平上产生了强烈且特异性的抗 H7 IgG 和 IgA 反应，以及 Th1/Th2/Th17 细胞反应。H7 诱导骨髓来源的树突状细胞的激活，并在免疫小鼠中引起显著的迟发型超敏反应（DTH）。重要的是，免疫小鼠完全免受 O157：H7 毒力株的攻击，存活的小鼠表现出高滴度的抗 H7 和 Stx 抗体。
这些结果表明，免疫接种可避免 HUS 结局，并引发针对其他毒力因子的特异性免疫反应。
