引起关注的B.1.427/B.1.429变种的SARS-CoV-2免疫逃避
Matthew McCallum1, Jessica Bassi2, Anna De Marco2
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
概括
一种新的SARS-CoV-2变种CAL.20C (B.1.427/B.1.429) 显示疫苗和过去感染的中和性减少. 其尖端蛋白中的关键突变重塑了N端域,避免了抗体反应.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 一种令人担忧的新型SARS-CoV-2变种CAL.20C (B.1.427/B.1.429) 出现了特定的突变.
- 这些突变包括信号中的S13I,N终端域中的W152C和受体结合域中的L452R.
研究的目的:
- 研究CAL.20C突变对抗体中和的影响.
- 了解抗体逃逸的结构基础.
主要方法:
- 使用接种疫苗和康复期患者的血进行中和测定.
- 对特定突变的单克隆抗体活性的评估.
- 质谱和结构研究分析尖端蛋白的变化.
主要成果:
- 与野生类型相比,对CAL.20C的中和标位降低了2至3. 5倍.
- 这种L452R突变影响了34种RBD特异单克隆抗体中的14种的中和.
- S13I和W152C突变导致10个NTD特异性单克隆抗体的中和完全丧失.
- 结构分析显示NTD抗原超位的重建.
结论:
- 由于其尖端蛋白的突变,CAL.20C变种表现出显著的免疫逃避.
- 突变重塑了NTD,导致某些抗体完全失去了中和作用.
- 这些发现凸显了SARS-CoV-2变种的不断变化的威胁以及更新疫苗或治疗方法的需要.
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