Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery.

Engineering the type III secretion system in non-replicating bacterial minicells for antigen delivery.
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DOI:
10.1038/ncomms2594
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发表时间:
2013
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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III 型蛋白分泌系统正在考虑用于疫苗开发,因为实际上任何蛋白抗原都可以被设计为由这些纳米机器递送到 I 类抗原呈递途径中,以刺激抗原特异性 CD8+ T 细胞。该系统使用的一个限制是它需要活毒力减弱的细菌,这可能妨碍其在某些人群中的使用,例如儿童和免疫功能低下的人。在这里,我们报告了源自细菌小细胞的非染色体、非复制纳米颗粒中鼠伤寒沙门氏菌 III 型分泌系统的工程。该工程系统显示出功能性,能够将异源抗原递送至 I 类抗原呈递途径,刺激体外和体内的免疫反应。该抗原递送平台为疫苗开发和细胞免疫治疗提供了一种新方法。
Type III protein secretion systems are being considered for vaccine development since virtually any protein antigen can be engineered for delivery by these nanomachines into the class I antigen presentation pathway to stimulate antigen-specific CD8+ T cells . A limitation in the use of this system is that it requires live virulence-attenuated bacteria, which may preclude its use in certain populations such as children and the immunocompromised. Here we report the engineering of the Salmonella Typhimurium type III secretion system in achromosomal, non-replicating nanoparticles derived from bacterial minicells. The engineered system is shown to be functional and capable of delivering heterologous antigens to the class I antigen presentation pathway stimulating immune responses both in vitro and in vivo. This antigen delivery platform offers a novel approach for vaccine development and cellular immunotherapy.
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