Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Instituto Milenio de Inmunología e Inmunoterapia, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Front Immunol. 2023 Jul 27;14:1186368. doi: 10.3389/fimmu.2023.1186368. eCollection 2023.
Shiga toxin-producing (STEC) is a foodborne pathogen that causes gastrointestinal infections, ranging from acute diarrhea and dysentery to life-threatening diseases such as Hemolytic Uremic Syndrome. Currently, a vaccine to prevent STEC infection is an unmet medical need.
We developed a chimeric protein-based vaccine targeting seven virulence factors of STEC, including the Stx2B subunit, Tir, Intimin, EspA, Cah, OmpT, and AggA proteins. Immunization of mice with this vaccine candidate elicited significant humoral and cellular immune responses against STEC. High levels of specific IgG antibodies were found in the serum and feces of immunized mice. However, specific IgA antibodies were not detected in either serum or feces. Furthermore, a significantly higher percentage of antigen-specific CD4+ T cells producing IFN-γ, IL-4, and IL-17 was observed in the spleens of immunized mice. Notably, the immunized mice showed decreased shedding of STEC O157:H7 and STEC O91:H21 strains and were protected against weight loss during experimental infection. Additionally, infection with the STEC O91:H21 strain resulted in kidney damage in control unimmunized mice; however, the extent of damage was slightly lower in immunized mice. Our findings suggest that IgG antibodies induced by this vaccine candidate may have a role in inhibiting bacterial adhesion and complement-mediated killing.
This study provides evidence that IgG responses are involved in the host defense against STEC. However, our results do not rule out that other classes of antibodies also participate in the protection against this pathogen. Additional work is needed to improve the protection conferred by our vaccine candidate and to elucidate the relevant immune responses that lead to complete protection against this pathogen.
产志贺毒素的大肠杆菌（STEC）是一种食源性病原体，可引起胃肠道感染，从急性腹泻和痢疾到溶血性尿毒症综合征等危及生命的疾病。目前，预防 STEC 感染的疫苗是一种未满足的医疗需求。
我们开发了一种针对 STEC 七种毒力因子的嵌合蛋白疫苗，包括 Stx2B 亚单位、Tir、Intimin、EspA、Cah、OmpT 和 AggA 蛋白。用这种疫苗候选物免疫小鼠可引起针对 STEC 的显著体液和细胞免疫应答。在免疫小鼠的血清和粪便中发现高水平的特异性 IgG 抗体。然而，在血清或粪便中均未检测到特异性 IgA 抗体。此外，在免疫小鼠的脾脏中观察到产生 IFN-γ、IL-4 和 IL-17 的抗原特异性 CD4+T 细胞的比例显著增加。值得注意的是，免疫小鼠表现出 STEC O157:H7 和 STEC O91:H21 菌株脱落减少，并在实验感染期间减轻体重减轻。此外，在对照未免疫的小鼠中，STEC O91:H21 株感染导致肾脏损伤；然而，在免疫小鼠中损伤程度略低。我们的研究结果表明，这种疫苗候选物诱导的 IgG 抗体可能在抑制细菌黏附和补体介导的杀伤中发挥作用。
本研究提供了证据表明 IgG 应答参与宿主对 STEC 的防御。然而，我们的结果并不排除其他类别的抗体也参与了对这种病原体的保护。需要进一步的工作来提高我们的疫苗候选物提供的保护，并阐明导致对这种病原体完全保护的相关免疫应答。
