SARS-CoV-2尖端的IgG桥接种子协同聚合是低亲和抗体的强烈中和的基础
Niannian Lv1,2,3, Peng Chen4, Xiaobin Dai5
1National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 8, 2025
概括
低亲和度抗体可以通过诱导病毒聚合来中和SARS-CoV-2变种,如Omicron JN.1. 这项研究揭示了一种超出高亲和度结合的强效抗体中和的新机制.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 病毒中和的机制研究往往忽略了低亲和力的抗体.
- 高亲和度抗体通常是优先考虑的,而低亲和度结合剂的探索较少.
研究的目的:
- 研究一种低亲和度,高强度的SARS-CoV-2抗体 (P5-1C8) 的机制.
- 了解弱结合抗体如何实现对病毒变异的强效中和.
主要方法:
- 对抗体-尖峰相互作用的结构和生物物理分析.
- 病毒样纳米粒子测试以评估抗体结合和聚合.
- 粗粒度分子动力学模拟. 粗粒度分子动力学模拟.
主要成果:
- P5-1C8显示弱的三元体结合 (KD = 225 nM),但强大的中和 (IC50 = 0.06 nM) 的奥米克朗JN.1.
- 抗体诱导了JN.1尖峰和病毒状颗粒的显著聚合.
- 分子动力学揭示了一条渐进的聚合途径,由弱抗体-尖峰接触播种.
结论:
- 弱结合抗体可以通过抗体诱导的病毒聚合来实现强大的中和.
- 本研究提出了通过聚合实现低亲和抗体中介中和的第一个机制框架.
- 这些发现扩大了对抗体功能的理解,并为抗体设计和评估提供了新的策略.
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