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通过干螺旋特异的人类抗体进行广泛的贝塔冠状病毒中和

Dora Pinto¹, Maximilian M Sauer², Nadine Czudnochowski³

¹Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.

Science (New York, N.Y.)

|August 4, 2021

概括

研究人员确定了五种强大的单克隆抗体 (mAbs),这些抗体针对包括SARS-CoV-2在内的β冠状病毒的干螺旋. 一种抗体,S2P6,表现出广泛的中和能力,并降低动物模型中的病毒载量,为泛β冠状病毒疫苗提供了有希望的途径.

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科学领域:

病毒学
免疫学
结构生物学

背景情况:

贝塔冠状病毒,包括SARS-CoV-2,由于人类的溢出和快速变种的出现,对公共健康构成重大威胁.
广泛的冠状病毒应对措施对于疫情准备至关重要.

研究的目的:

识别和描述针对多种β冠状病毒的尖端糖蛋白的交叉反应单克隆抗体.
阐明这些抗体广泛中和的结构和功能基础.

主要方法:

从COVID-19康复患者中分离和鉴定单克隆抗体.
结构研究 (例如,冷-EM,X射线晶体) 来确定抗体-抗原相互作用.
在实验室中使用伪型病毒进行中和测试,以及在动物模型 (仓鼠) 中进行功能测试.

主要成果:

鉴定出五种单克隆抗体 (mAbs) 与各种β冠状病毒尖端糖蛋白的干螺旋交叉反应.
通过抑制膜融合,S2P6 mAb表现出对三种亚种病毒的广泛中和.
结构分析揭示了S2P6广泛交叉反应的分子基础.
通过中和和Fc介导的功能,S2P6在减少仓鼠的SARS-CoV-2病毒负担方面表现出有效性.

结论:

干螺旋抗体虽然罕见且特异性通常较窄,但可以通过体质突变等机制实现广泛的中和.
这些发现为以结构为导向的泛β冠状病毒疫苗开发提供了基础,以广泛保护各种冠状病毒.