英国牛津大学Gavin R. Screaton等研究人员合作完成SARS-CoV-2受体结合结构域的抗原剖析。相关论文于2021年2月18日在线发表于国际学术期刊《细胞》。
研究人员确定了377种识别病毒突刺的人类单克隆抗体（mAbs），主要集中于80种与受体结合结构域（RBD）结合的抗体。研究人员设计了一种竞争数据驱动的方法来绘制RBD结合位点。结果表明，尽管抗体结合位点广泛分布，但中和抗体的结合却是集中的，几乎所有具有高度抑制性的mAb（IC50<0.1μg/ml）都能阻断受体相互作用，除了在N末端域结合独特表位的受体。这些中和单克隆抗体中的许多都使用公共V基因，并且接近种系。
研究人员通过X射线晶体学和19种Fab抗原结构的冷冻电镜来剖析了这一庞大的抗体识别结构基础。研究人员发现了一些有效抑制性抗体的新型结合模式，并证明了强中和性单克隆抗体可以在动物模型中进行预防或治疗。
据介绍，抗体对于提供SARS-CoV-2的免疫保护至关重要，其中一些可以紧急用作治疗剂。
附：英文原文
Title: The antigenic anatomy of SARS-CoV-2 receptor binding domain
Author: Wanwisa Dejnirattisai, Daming Zhou, Helen M. Ginn, Helen M.E. Duyvesteyn, Piyada Supasa, James Brett Case, Yuguang Zhao, Thomas S. Walter, Alexander J. Mentzer, Chang Liu, Beibei Wang, Guido C. Paesen, Jose Slon-Campos, César López-Camacho, Natasha M. Kafai, Adam L. Bailey, Rita E. Chen, Baoling Ying, Craig Thompson, Jai Bolton, Alex Fyfe, Sunetra Gupta, Tiong Kit Tan, Javier Gilbert-Jaramillo, William James, Michael Knight, Miles W. Carroll, Donal Skelly, Christina Dold, Yanchun Peng, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Paul Klenerman, Nigel Temperton, David R. Hall, Mark A. Williams, Neil G. Paterson, Felicity K.R. Bertram, C. Alistair Seibert, Daniel K. Clare, Andrew Howe, Julika Raedecke, Yun Song, Alain R. Townsend, Kuan-Ying A. Huang, Elizabeth E. Fry, Juthathip Mongkolsapaya, Michael S. Diamond, Jingshan Ren, David I. Stuart, Gavin R. Screaton
Issue&Volume: 2021-02-18
Abstract: Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike, and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50<0.1μg/ml) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryo-electron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.
DOI: 10.1016/j.cell.2021.02.032
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00221-X