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人类冠状病毒HKU1中和单克隆抗体向TMPRSS2受体结合部位内和周围的多种表位

Lingshu Wang¹, Jeswin Joseph², Sheena Vasquez³

¹Vaccine Research Center; National Institutes of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of America.

bioRxiv : the preprint server for biology

|November 24, 2025

概括

研究人员描述了人类冠状病毒HKU1 (HCoV-HKU1) 与单克隆抗体的尖端相互作用. 他们发现了强大的中和抗体,准受体结合域,这对于开发通用冠状病毒疫苗至关重要.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
疫苗开发疫苗开发

背景情况:

流行的人类冠状病毒 (HCoV),包括HCoV-HKU1,导致严重的呼吸系统疾病,但缺乏向疫苗.
对于HCoV-HKU1的抗原格局仍然不太了解,这阻碍了疫苗的设计.

研究的目的:

描述HCoV-HKU1尖端蛋白和单克隆抗体 (mAbs) 之间的相互作用.
为潜在的疫苗开发确定HCoV-HKU1上的中和表位.

主要方法:

从大流行前的HCoV-HKU1康复的外周血液单核细胞 (PBMCs) 中分离了14mAbs.
结构和功能研究分析mAb结合点和中和能力.
与受体结合域 (RBD) 的抗体相互作用及其与TMPRSS的接触的特征2.

主要成果:

mAbs针对尖端蛋白的不同区域,包括RBD,N终端域和S2子单元.
确定了三组RBD特异的mAbs,它们针对TMPRSS2受体结合部位周围的不同部位.
描述了强大的中和mAbs,包括一个阻断TMPRSS2参与 (H501-022) 和其他结合保存或依赖形状的表位素 (H501-008,H501-018).

结论:

这些代表了来自康复期捐赠者的第一个类型特定的HCoV-HKU1 mAbs.
这些发现为HCoV-HKU1中和机制提供了分子洞察力.
突出HCoV和大流行CoV之间的抗原差异对于通用冠状病毒疫苗设计至关重要.

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