缺少超变区的截断的鞭毛蛋白:改善免疫反应和辅助性的结构基础
Shengmei Pang1, Longlong Wang1, Mei Liu1
1College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Joint Laboratory for International Cooperation in Agriculture and Agricultural Product Safety, Ministry of Education, Yangzhou 225009, China; Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, Jiangsu, China.
缺少超变区的截断的细菌鞭毛体保留了强大的免疫调节特性. 这些鞭毛素衍生物增强免疫反应,并显示出作为改善免疫性疫苗辅助剂的前景.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 微生物病原体的产生
背景情况:
- 细菌鞭毛蛋白是强大的免疫调节剂,具有疫苗辅助剂的潜力.
- 旗蛋白通过托尔样受体5 (TLR5) 和NLRC4炎症酶信号激活先天性和适应性免疫.
- 了解鞭毛素的结构-功能关系是优化辅助性质的关键.
研究的目的:
- 为了研究截断的鞭毛素衍生物对TLR5激活的影响.
- 评估缺乏特定域的鞭毛蛋白突变体的辅助性质.
- 为了确定对免疫激活和辅助疗效至关重要的鞭毛蛋白域.
主要方法:
- 从大肠杆菌 (EHEC EDL933) 产生截断的鞭毛蛋白突变体.
- 在体外评估通过鞭毛素衍生物激活TLR5.
- 在体内评估使用模型抗原的免疫辅助作用.
主要成果:
- 缺乏超变区 (HVR) 的旗蛋白变体,但保留终端域 (FliCH7,FliCNC,FliCH7-FaeG,FliCNC-FaeG) 显著增强了TNF-α和IL-8的产生.
- 该FliCNC突变显示TLR5激活与本地鞭毛蛋白相比较.
- 当被用作辅助剂或融合蛋白时,截断的鞭毛素诱导了更高的抗体标位.
结论:
- HVR对于鞭毛素的免疫辅助活性来说并不重要.
- 保存的终端区域对于TLR5激活至关重要.
- 优化的鞭毛蛋白衍生物,特别是那些缺乏HVR的衍生物,为疫苗开发提供了一个强大的平台,以增强免疫反应.
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