一种细菌mRNA溶解介导的货物释放疫苗系统,用于调节细胞质监测和优化抗原输送
Yu-An Li1,2, Yanni Sun1,2, Yuqin Zhang1,2
1College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225000, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|October 22, 2023
概括
一种新的沙门氏菌mRNA干扰酶调节载体 (SIRV) 系统通过诱导抗原释放的自溶和激活免疫反应来增强体内蛋白质的输送. 这种工程细菌载体提高了疫苗的疗效和动物的存活率.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
背景情况:
- 基于载体的体内蛋白质输送对于疫苗至关重要,但受到货物释放的限制.
- 由于被困的外来抗原,目前的平台努力实现最佳的治疗效益.
研究的目的:
- 开发一种工程化细菌载体系统,以有效地在体内输送蛋白质并改善治疗结果.
- 通过实现对外抗原的控制释放来克服当前平台的局限性.
主要方法:
- 设计了一种沙门氏菌mRNA干扰酶调节载体 (SIRV) 系统.
- 嵌入的基因电路用于自溶解和cGAS-STING通路的激活.
- 利用延迟的MazF干扰酶合成来调节mRNA裂变和抗原释放.
主要成果:
- 实现了外来抗原输送的36倍增加.
- 证明了适度的炎酶激活和抗原呈现细胞 (APC) 的显著成熟.
- 传递SaoA抗原的细菌在小鼠和猪模型中显示出高免疫性和安全性,改善了对Streptococcus suis的生存率.
结论:
- 该SIRV系统使有效的细胞内蛋白质输送和强烈的免疫反应.
- 该平台可使用各种细菌物种生成多样化的细胞内蛋白质输送系统.
- 该SIRV系统代表了疫苗开发和治疗性蛋白质输送的重大进步.
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