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一种治疗性非自我反应性SARS-CoV-2抗体在COVID-19仓鼠模型中保护肺部病理

Jakob Kreye¹, S Momsen Reincke², Hans-Christian Kornau³

¹German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany; Helmholtz Innovation Lab BaoBab (Brain Antibody-omics and B-cell Lab), 10117 Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

|October 15, 2020

概括

研究人员发现了对导致COVID-19的病毒SARS-CoV-2的强效中和抗体. 一个抗体,CV07-209,表现出强烈的中和和保护仓鼠,显示出COVID-19治疗方法的前景.

科学领域:

免疫学
病毒学
结构生物学

背景情况:

严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 导致COVID-19,这是一个具有呼吸系统和多器官影响的流行病.
了解病毒中和抗体及其目标对于COVID-19治疗和疫苗开发至关重要.

研究的目的:

描述SARS-CoV-2中和单克隆抗体 (mAbs) 和它们的表位.
评估对抗SARS-CoV-2的有效中和mAbs的治疗潜力.

主要方法:

从10名COVID-19患者中对598名人类mAbs进行查,以确定中和抗体.
使用X射线晶体学对mAb受体结合域复合物的结构分析.
在SARS-CoV-2感染的仓鼠模型中进行体内疗效研究.

主要成果:

确定了40个强度中和的mAbs,其中CV07-209显示强度中和 (IC50=3. 1 ng/ mL).
晶体结构显示mAbs直接阻断了ACE2受体的附着.
CV07-209证明了对仓鼠的SARS-CoV-2的预防性和治疗性保护,减少了症状和肺病理.

结论:

在SARS-CoV-2感染期间产生的非自我反应,病毒中和的mAbs代表了一个有前途的治疗策略.
这些抗体的特征提供了对COVID-19病原和基于抗体的干预措施的见解.

关键词:

美国冠状病毒自动反应性晶体结构哈姆斯特模型单克隆抗体中和抗体暴露后的情况自体抗原自动反应性

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