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发现和描述一种泛贝塔冠状病毒S2结合抗体

Nicole V Johnson¹, Steven C Wall^2,3, Kevin J Kramer^2,3

¹Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

bioRxiv : the preprint server for biology

|January 31, 2024

概括

研究人员在S2尖端蛋白子单元上发现了一个广泛保存的冠状病毒表位. 这种非中和抗体54043-5显示出Fc-依赖的抗病毒活性,并对小鼠的SARS-CoV-2进行了保护.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
结构生物学结构生物学

背景情况:

三个主要的冠状病毒溢出事件导致了致命的流行病/流行病.
新型冠状病毒的出现需要广泛的干预措施来应对流行病的准备.

研究的目的:

识别和描述针对保存的冠状病毒表位的新型人类抗体.
研究非中和抗体所赋予的保护机制.

主要方法:

使用LIBRA-seq从B细胞中分离出50个人类冠状病毒抗体.
使用冷电子显微镜 (cryo-EM) 来确定抗体-S2尖端蛋白复合物的结构.
用小鼠模型来评估体内对SARS-CoV-2挑战的保护.

主要成果:

抗体54043-5与α,β和delta冠状病毒的S2亚单元结合,向一个保存的表位.
冷-EM结构揭示了S2子单元的顶部的结合部位,这种结合部位在贝塔冠状病毒中保存着.
非中和抗体54043-5诱导了Fc依赖性抗病毒反应 (ADCC,ADCP) 并在被设计为增强Fc功能时在小鼠SARS-CoV-2模型中给予保护.

结论:

在冠状病毒的S2子单元内发现了一个广泛保存的表位.
非中和抗体可以通过Fc依赖机制引起保护性免疫.
这些发现为开发泛冠状病毒干预措施提供了见解.

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