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N-终端域抗原映射显示了SARS-CoV-2的易受伤害的地方

Matthew McCallum¹, Anna De Marco², Florian A Lempp³

¹Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

|March 24, 2021

概括

研究人员发现了针对SARS-CoV-2尖端蛋白的N终端域 (NTD) 的强效中和抗体. 这些抗体提供了对SARS-CoV-2感染的保护,对未来的疫苗开发至关重要.

科学领域:

病毒学和免疫学
疫苗开发
结构生物学

背景情况:

SARS-CoV-2尖端 (S) 糖蛋白的受体结合域 (RBD) 是COVID-19患者中和抗体的主要目标.
关于中和抗体针对RBD以外的表位和它们的保护作用的知识有限.

研究的目的:

针对SARS-CoV-2 S N-终端域 (NTD) 的人类单克隆抗体 (mAbs) 的鉴定和特征.
研究特异性NTD抗体的中和能力和保护潜力.
确定NTD的抗原景观,并确定关键的中和超位点.

主要方法:

从针对 SARS-CoV-2 NTD 的记忆B细胞中分离和鉴定了 41 种人类单克隆抗体 (mAbs).
对NTD进行抗原映射以确定保存的中和超位.
在试验室中评估中和效能,抑制细胞对细胞的融合,以及效应器功能.
在叙利亚仓鼠体内进行的保护研究对SARS-CoV-2提出了挑战.

主要成果:

已识别的NTD特异性mAbs的一个子集证明了SARS-CoV-2的超强中和.
一个抗原地图揭示了所有特征性NTD特定的中和mAbs所识别的保存的超位 (位点i).
这些特定于NTD的mAbs抑制了病毒的传播,激活了效应器功能,并且在一个仓鼠模型中提供了保护,尽管突变突变出现了.
关键的SARS-CoV-2变种 (B.1.1.7,B.1.351,P.1) 在NTD超位表现出突变,表明进化压力.

结论:

在SARS-CoV-2 NTD中,存在被强大的中和抗体准的保存超位.
特定于NTD的中和mAbs对抗SARS-CoV-2的保护性免疫有显著的贡献.
这些发现强调了针对NTD的抗体对于开发针对SARS-CoV-2及其变种的有效疫苗和治疗药物的重要性.

关键词:

美国 N终端域其他国家冠状病毒记忆B细胞中和抗体标杆糖蛋白

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