| Literature DB >> 33756110 |
Wanwisa Dejnirattisai1, Daming Zhou2, Helen M Ginn3, Helen M E Duyvesteyn2, Piyada Supasa1, James Brett Case4, Yuguang Zhao2, Thomas S Walter2, Alexander J Mentzer5, Chang Liu6, Beibei Wang1, Guido C Paesen2, Jose Slon-Campos1, César López-Camacho1, Natasha M Kafai7, Adam L Bailey8, Rita E Chen7, Baoling Ying4, Craig Thompson9, Jai Bolton10, Alex Fyfe9, Sunetra Gupta9, Tiong Kit Tan11, Javier Gilbert-Jaramillo12, William James12, Michael Knight12, Miles W Carroll13, Donal Skelly14, Christina Dold15, Yanchun Peng11, Robert Levin16, Tao Dong17, Andrew J Pollard18, Julian C Knight5, Paul Klenerman19, Nigel Temperton20, David R Hall3, Mark A Williams3, Neil G Paterson3, Felicity K R Bertram3, C Alistair Siebert3, Daniel K Clare3, Andrew Howe3, Julika Radecke3, Yun Song3, Alain R Townsend21, Kuan-Ying A Huang22, Elizabeth E Fry2, Juthathip Mongkolsapaya23, Michael S Diamond24, Jingshan Ren25, David I Stuart26, Gavin R Screaton27.
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 < 0.1 μg/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 cryoelectron 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.Entities:
Keywords: coronavirus, SARS-CoV-2, anti-RBD antibody, receptor binding domain, antibody, immune responses, virus structure
Mesh：
Substances：
Year: 2021 PMID： 33756110 PMCID： PMC7891125 DOI： 10.1016/j.cell.2021.02.032
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582