Institute of Virology, University of Zurich, Winterthurerstrasse 266a, 8057, Zurich, Switzerland.
Laboratory for Animal Model Pathology, Institute of Pathology, Vetsuisse, University of Zurich, Zurich, Switzerland.
Microb Cell Fact. 2018 Nov 26;17(1):187. doi: 10.1186/s12934-018-1030-8.
We previously engineered Bacillus subtilis to express an antigen of interest fused to TasA in a biofilm. B. subtilis has several properties such as sporulation, biofilm formation and probiotic ability that were used for the oral application of recombinant spores harboring Echinococcus granulosus paramyosin and tropomyosin immunogenic peptides that resulted in the elicitation of a specific humoral immune response in a dog model.
In order to advance our understanding of the research in oral immunization practices using recombinant B. subtilis spores, we describe here an affordable animal model. In this study, we show clear evidence indicating that a niche is required for B. subtilis recombinant spores to colonize the densely populated mice intestinal microbiota. The reduction of intestinal microbiota with an antibiotic treatment resulted in a positive elicitation of local humoral immune response in BALB/c mice after oral application of recombinant B. subtilis spores harboring TasA fused to E. granulosus (102-207) EgTrp immunogenic peptide. Our results were supported by a lasting prevalence of spores in mice feces up to 50 days after immunization and by the presence of specific secretory IgA, isolated from feces, against E. granulosus tropomyosin.
The reduction of mouse intestinal microbiota allowed the elicitation of a local humoral immune response in mice after oral application with spores of B. subtilis harboring immunogenic peptides against E. granulosus.
我们之前通过将感兴趣的抗原与 TasA 融合表达在生物膜中来工程化枯草芽孢杆菌。枯草芽孢杆菌具有几种特性,如孢子形成、生物膜形成和益生菌能力,这些特性被用于口服应用携带细粒棘球蚴副肌球蛋白和原肌球蛋白免疫肽的重组孢子,导致在犬模型中引发特异性体液免疫反应。
为了深入了解使用重组枯草芽孢杆菌孢子进行口服免疫的研究,我们在这里描述了一种经济实惠的动物模型。在这项研究中,我们清楚地证明了需要一个小生境才能使枯草芽孢杆菌重组孢子在密集的小鼠肠道微生物群中定植。抗生素处理减少肠道微生物群后,在口服应用携带 TasA 融合的细粒棘球蚴(102-207)EgTrp 免疫肽的重组枯草芽孢杆菌孢子后,在 BALB/c 小鼠中引发了局部体液免疫反应。我们的结果得到了以下结果的支持:在免疫后 50 天内,小鼠粪便中持续存在孢子,并且从粪便中分离出针对细粒棘球蚴原肌球蛋白的特异性分泌型 IgA。
减少小鼠肠道微生物群可以在口服应用携带针对细粒棘球蚴的免疫肽的枯草芽孢杆菌孢子后在小鼠中引发局部体液免疫反应。