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Germination of the spore in the gastrointestinal tract provides a novel route for heterologous antigen delivery

机译:胃肠道中的孢子萌发为异源抗原递送提供了一条新途径

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We have evaluated the potential of endospores of the Gram-positive bacterium Bacillus subtilis as an oral vaccine delivery system. The key features of the B. subtilis spore as a vaccine are, non-pathogenicity, advanced cloning tools, extreme robustness, long-term storage properties and its current use as a probiotic for both humans and animals. We have shown previously that the spore germinates in the small intestine of the mouse and have exploited this attribute for heterologous antigen delivery in this work. The first part of this study was to evaluate the fate of spores in vivo as well as under simulated gut conditions. This showed that spores were extremely robust with most being excreted in the faeces. Using a recombinant gene expressing high levels of P-galactosidase specifically in the germinated spore (vegetative cell) we showed that spores administered orally could elicit P-galactosidase-specific local and systemic immune responses. This demonstrated proof of principle that the germinating spore might be effective in the safe delivery of antigens across the stomach barrier. Interestingly, analysis of IgG subclasses suggested a potential bias towards a Th1 response and the involvement of cellular immunity.
机译:我们已经评估了革兰氏阳性细菌枯草芽孢杆菌的内生孢子作为口服疫苗递送系统的潜力。枯草芽孢杆菌孢子作为疫苗的关键特征是非致病性,先进的克隆工具,极强的耐用性,长期储存特性以及目前作为人和动物益生菌的用途。先前我们已经表明,孢子在小鼠的小肠中发芽,并且在这项工作中利用了该属性进行异源抗原递送。这项研究的第一部分是评估体内以及模拟肠道条件下孢子的命运。这表明孢子极强壮,大部分排泄在粪便中。使用在发芽孢子(营养细胞)中特异性表达高水平P-半乳糖苷酶的重组基因,我们表明口服给予的孢子可以引起P-半乳糖苷酶特异性的局部和全身免疫应答。这证明了原理证明,发芽孢子可以有效地跨胃屏障安全递送抗原。有趣的是,对IgG亚类的分析表明对Th1反应和细胞免疫功能的潜在偏倚。

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