BACKGROUND Spore-forming bacteria of the Bacillus genus are widely used probiotics known to exert their beneficial effects also through the stimulation of the host immune response. The oral delivery of B. toyonensis spores has been shown to improve the immune response to a parenterally administered viral antigen in mice, suggesting that probiotics may increase the efficiency of systemic vaccines. We used the C fragment of the tetanus toxin (TTFC) as a model antigen to evaluate whether a treatment with B. toyonensis spores affected the immune response to a mucosal antigen. RESULTS Purified TTFC was given to mice by the nasal route either as a free protein or adsorbed to B. subtilis spores, a mucosal vaccine delivery system proved effective with several antigens, including TTFC. Spore adsorption was extremely efficient and TTFC was shown to be exposed on the spore surface. Spore-adsorbed TTFC was more efficient than the free antigen in inducing an immune response and the probiotic treatment improved the response, increasing the production of TTFC-specific secretory immunoglobin A (sIgA) and causing a faster production of serum IgG. The analysis of the induced cytokines indicated that also the cellular immune response was increased by the probiotic treatment. A 16S RNA-based analysis of the gut microbial composition did not show dramatic differences due to the probiotic treatment. However, the abundance of members of the Ruminiclostridium 6 genus was found to correlate with the increased immune response of animals immunized with the spore-adsorbed antigen and treated with the probiotic. CONCLUSION Our results indicate that B. toyonensis spores significantly contribute to the humoral and cellular responses elicited by a mucosal immunization with spore-adsorbed TTFC, pointing to the probiotic treatment as an alternative to the use of adjuvants for mucosal vaccinations.

中文翻译：

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益生菌治疗可提高经鼻孢子吸附的TTFC的鼻腔输送诱导的免疫反应。

背景技术芽孢杆菌属的形成孢子的细菌是广泛使用的益生菌，已知其也通过刺激宿主免疫应答而发挥其有益作用。已显示口服粉状芽孢杆菌孢子可改善小鼠对肠胃外施用的病毒抗原的免疫反应，这表明益生菌可提高全身疫苗的效率。我们使用破伤风毒素（TTFC）的C片段作为模型抗原来评估用蟾蜍芽孢杆菌的孢子治疗是否影响对粘膜抗原的免疫反应。结果纯化的TTFC以游离蛋白或吸附到枯草芽孢杆菌孢子的形式经鼻途径给予小鼠，一种经证实的粘膜疫苗递送系统对包括TTFC在内的多种抗原均有效。孢子吸附非常有效，并且TTFC被证明暴露在孢子表面。孢子吸附的TTFC在诱导免疫反应方面比游离抗原更有效，益生菌处理改善了反应，增加了TTFC特异性分泌型免疫球蛋白A（sIgA）的产生，并导致血清IgG的产生更快。对诱导的细胞因子的分析表明，益生菌处理还提高了细胞免疫应答。基于16S RNA的肠道微生物组成分析未显示由于益生菌处理而产生的显着差异。但是，发现Ruminiclostridium 6属成员的丰度与用孢子吸附抗原免疫并经益生菌处理的动物的免疫应答增加有关。