近日，美国华盛顿大学David Veesler等研究人员合作绘制出SARS-CoV-2的N端结构域抗原图谱。这一研究成果于2021年3月16日在线发表在国际学术期刊《细胞》上。

研究人员表示，SARS-CoV-2突刺（S）糖蛋白包含一个免疫优势受体结合域（RBD），COVID-19患者血浆中大多数中和抗体（Abs）都以此为靶标。关于中和Abs与RBD外部抗原决定簇的结合及其对保护的贡献知之甚少。

研究人员描述了41种源自记忆B细胞的人单克隆抗体（mAb），它们识别SARS-CoV-2 S N端结构域（NTD），并显示其中的一个亚群能超强地中和SARS-CoV-2。研究人员定义了SARS-CoV-2 NTD的抗原图谱，并鉴定了由所有已知的NTD特异性中和单克隆抗体识别的超级位点（指定位点i）。

这些单克隆抗体可抑制细胞间融合，激活效应子功能，并保护叙利亚仓鼠免受SARS-CoV-2攻击，即使在某些动物中选择逃避突变体也是如此。

实际上，包括B.1.1.7、B.1.351和P1谱系在内的几种SARS-CoV-2变体在NTD超级位点内经常发生突变，这表明持续的选择性压力以及NTD特异性中和mAb对保护性免疫和疫苗设计的重要性。 

附：英文原文

Title: N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2

Author: Matthew McCallum, Anna De Marco, Florian A. Lempp, M. Alejandra Tortorici, Dora Pinto, Alexandra C. Walls, Martina Beltramello, Alex Chen, Zhuoming Liu, Fabrizia Zatta, Samantha Zepeda, Julia di Iulio, John E. Bowen, Martin Montiel-Ruiz, Jiayi Zhou, Laura E. Rosen, Siro Bianchi, Barbara Guarino, Chiara Silacci Fregni, Rana Abdelnabi, Shi-Yan Caroline Foo, Paul W. Rothlauf, Louis-Marie Bloyet, Fabio Benigni, Elisabetta Cameroni, Johan Neyts, Agostino Riva, Gyorgy Snell, Amalio Telenti, Sean P.J. Whelan, Herbert W. Virgin, Davide Corti, Matteo Samuele Pizzuto, David Veesler

Issue&Volume: 2021-03-16

Abstract: 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 SARS-CoV-2 variants, including the B.1.1.7, B.1.351 and P1 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.

DOI: 10.1016/j.cell.2021.03.028

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00356-1