欧米克朗逃脱了现有的大部分SARS-CoV-2中和抗体
Yunlong Cao1,2, Jing Wang3,4, Fanchong Jian3,5
1Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, P. R. China. yunlongcao@pku.edu.cn.
Nature
|January 11, 2022
概括
SARS-CoV-2 的 Omicron 变种在很大程度上避开了中和抗体,超过 85% 的抗体有效性降低了. 针对保存的萨尔贝科病毒区域的抗体对Omicron免疫逃避最有效.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- SARS-CoV-2 Omicron 变种 (B.1.1.529) 在其受体结合域 (RBD) 中具有众多突变.
- 了解Omicron的免疫逃避机制对于开发有效的治疗方法和疫苗至关重要.
研究的目的:
- 调查Omicron的突变如何影响现有的中和抗体的有效性.
- 根据它们对Omicron逃生突变的敏感性对抗体进行分类.
主要方法:
- 使用高通量酵母显示查来评估247个人类抗RBD中和抗体对抗Omicron突变.
- 使用无监督聚类将抗体分为表位类 (A- F).
- 为了评估抗体的有效性,进行了Omicron伪病毒中和试验.
主要成果:
- 奥米克龙突变,特别是K417N,G446S,E484A和Q493R,显著地逃脱了针对ACE2结合动机的抗体 (A-D组).
- 具有广泛沙贝科病毒活性的抗体 (E组和F组) 呈现下降但保持中和,尽管一些仍受到G339D,N440K和S371L等突变的影响.
- 超过85%的测试中和抗体被Omicron脱离,多种突变具有协同效应.
- 一些基于抗体的药物 (例如LY-CoV016, REGN10933) 对Omicron失去显著的中和效力,而其他药物 (VIR-7831, DXP-604) 保持了降低的有效性.
结论:
- 由于其RBD突变,Omicron表现出大量的幽默免疫逃避.
- 针对保存的沙贝科病毒区域的中和抗体对Omicron具有更大的有效性.
- 这些发现有助于开发下一代抗体疗法和针对当前和未来SARS-CoV-2变种有效的疫苗.
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