祖先β-CoV支架抗原的设计,结构和血结合
David Hueting1,2, Karen Schriever1,2, Rui Sun3
1School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
Nature communications
|October 16, 2023
概括
科学家们将祖先的冠状病毒尖端蛋白重建成稳定抗原 (AnSA). 这些AnSA与COVID-19患者的血接触,但不与ACE2受体接触,为疫苗开发提供了潜在的新途径.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 包括SARS-CoV-2在内的冠状病毒的尖端蛋白质是疫苗和治疗的关键目标.
- 了解尖端蛋白的祖先结构可以提供有关其演变及其潜在漏洞的见解.
研究的目的:
- 为了重建祖先的冠状病毒尖端蛋白作为稳定抗原 (AnSAs).
- 描述这些AnSAs的结构和免疫特性.
- 评估ANSA作为疫苗支架的潜力.
主要方法:
- 冠状病毒尖端蛋白的祖先序列重建.
- 稳定和可溶性AnSAs的表达和净化.
- 电子显微镜 (Cryo-EM) 用于结构分析.
- 用康复期血和ACE2受体进行结合测试.
- 在免疫器官模型中评估免疫反应.
主要成果:
- 稳定和高度溶解的AnSAs被成功生成.
- AnSAs与康复的COVID-19患者的血结合,但不与人类的ACE2受体结合.
- 高分辨率的冷电磁结构揭示了AnSAs的封闭的融合前形态.
- 在一个有机体模型中,AnSA-5诱导了针对野生类型和变种RBD的宽谱免疫反应.
- 用野生类型的RBD取代祖先的RBD恢复了ACE2结合并增加了康复期血相互作用.
结论:
- AnSAs是稳定的,可溶性的,结构上定义良好的抗原.
- AnSAs代表了开发针对冠状病毒的广谱疫苗的有希望的平台.
- 可以修改AnSA支架以恢复特定的结合性质,突出其多功能性.
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