Clostridioides difficile is a Gram-positive, spore-forming bacterium that causes a severe intestinal infection. Spores of this pathogen enter in the human body through the oral route, interact with intestinal epithelial cells and persist in the gut. Once germinated, the vegetative cells colonize the intestine and produce toxins that enhance a strong immune response that perpetuate the disease. Therefore, spores are major players of the infection and ideal targets of new therapeutic treatments. In this context, spore surface proteins of C. difficile, are potential antigens for the development of vaccines targeting C. difficile spores. Here we report that the C-terminal domain of the spore surface protein BclA3, BclA3CTD, was identified as an antigenic epitope, over-produced in Escherichia coli and tested as an immunogen in mice. To increase antigen stability and efficiency, BclA3CTD was also exposed on the surface of B. subtilis spores, a well-established mucosal vaccine delivery system. In the experimental conditions used in this study, free BclA3CTD induced antibody production in mice and attenuated some CDI symptoms after a challenge with the pathogen, while the spore-displayed antigen resulted less effective. Although dose regimen and immunization route need to be optimized, our results suggest BclA3CTD as a potentially effective antigen to develop a new vaccination strategy targeting C. difficile spores.

中文翻译：

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用BclA3的C末端域进行鼻腔免疫可诱导特异性IgG产生并减轻感染艰难梭菌孢子的小鼠的疾病症状

艰难梭菌是引起严重肠道感染的革兰氏阳性孢子形成细菌。该病原体的孢子通过口服途径进入人体，与肠道上皮细胞相互作用，并在肠道中持续存在。一旦发芽，营养细胞就会在肠道内定殖并产生毒素，从而增强强烈的免疫反应，使疾病永存。因此，孢子是感染的主要参与者，是新疗法的理想靶标。在这种情况下，艰难梭菌的孢子表面蛋白是用于开发针对艰难梭菌孢子的疫苗的潜在抗原。在这里我们报告孢子表面蛋白BclA3，BclA3CTD的C末端域被鉴定为抗原表位，在大肠杆菌中过量产生，并在小鼠中作为免疫原进行了测试。为了增加抗原的稳定性和效率，BclA3CTD也暴露在枯草芽孢杆菌孢子表面上，这是一种完善的粘膜疫苗递送系统。在这项研究中使用的实验条件下，在病原体攻击后，游离的BclA3CTD诱导了小鼠中抗体的产生，并减轻了一些CDI症状，而孢子展示的抗原产生的效果较差。尽管剂量方案和免疫途径需要优化，但我们的结果表明BclA3CTD是潜在的有效抗原，可用于开发针对艰难梭菌孢子的新型疫苗接种策略。病原菌攻击后，游离的BclA3CTD诱导了小鼠中抗体的产生，并减轻了一些CDI症状，而孢子展示的抗原产生的效果较差。尽管剂量方案和免疫途径需要优化，但我们的结果表明BclA3CTD是潜在的有效抗原，可用于开发针对艰难梭菌孢子的新型疫苗接种策略。病原菌攻击后，游离的BclA3CTD诱导了小鼠中抗体的产生，并减轻了一些CDI症状，而孢子展示的抗原产生的效果较差。尽管剂量方案和免疫途径需要优化，但我们的结果表明BclA3CTD是潜在的有效抗原，可用于开发针对艰难梭菌孢子的新型疫苗接种策略。