N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
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DOI：
10.1101/2021.01.14.426475
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发表时间：
2021-04-29
期刊：
影响因子：
64.5
通讯作者：
Veesler, David
中科院分区：
文献类型：
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作者：
McCallum, Matthew;De Marco, Anna;Veesler, David
SARS-CoV-2刺突（S）糖蛋白含有一个免疫显性受体结合结构域（RBD），可被COVID-19患者血浆中的大多数中和抗体（Ab）靶向。关于结合RBD外表位的中和抗体及其对保护的贡献知之甚少。在这里，我们描述了41人单克隆抗体（单克隆抗体）来自记忆B细胞，识别SARS-CoV-2 S N-末端结构域（NTD），并显示，他们的一个子集中和SARS-CoV-2超强效。我们定义了SARS-CoV-2 NTD的抗原图，并确定了所有已知NTD特异性中和mAb识别的超位点（指定位点i）。这些单克隆抗体抑制细胞间融合，激活效应子功能，并保护叙利亚仓鼠免受SARS-CoV-2的攻击，尽管在一些动物中选择了逃逸突变体。事实上，包括B.1.1.7、B.1.351和P.1谱系在内的几种SARSCoV-2变体在NTD超位点内具有频繁的突变，这表明了持续的选择压力以及NTD特异性中和mAb对保护性免疫和疫苗设计的重要性。
The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARSCoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.