The antigenic anatomy of SARS-CoV-2 receptor binding domain
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 met...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2021
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| _version_ | 1797056385459945472 |
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| author | Dejnirattisai, W Zhou, D Ginn, HM Duyvesteyn, HME Spasa, D Case, JB Zhao, Y Walter, TS Mentzer, AJ Liu, C Wang, B Paesen, GC Slon-Campus, J López-Camacho, C Kafai, NM Bailey, AL Chen, RE Ying, B Thompson, C Bolton, J Fyfe, A Gupta, S Tan, TK Gilbert-Jaramillo, J James, W Knight, M Carroll, MW Skelly, D Dold, C Peng, Y Levin, R Dong, T Pollard, AJ Knight, JC Klenerman, P Temperton, N Hall, DR Williams, MA Paterson, NG Bertram, FKR Seibert, CA Clare, DK Howe, A Raedecke, J Song, Y Townsend, AR Huang, K-YA Fry, EE Mongkolsapaya, J Diamond, MS Ren, J Stuart, DI Screaton, GR |
| author_facet | Dejnirattisai, W Zhou, D Ginn, HM Duyvesteyn, HME Spasa, D Case, JB Zhao, Y Walter, TS Mentzer, AJ Liu, C Wang, B Paesen, GC Slon-Campus, J López-Camacho, C Kafai, NM Bailey, AL Chen, RE Ying, B Thompson, C Bolton, J Fyfe, A Gupta, S Tan, TK Gilbert-Jaramillo, J James, W Knight, M Carroll, MW Skelly, D Dold, C Peng, Y Levin, R Dong, T Pollard, AJ Knight, JC Klenerman, P Temperton, N Hall, DR Williams, MA Paterson, NG Bertram, FKR Seibert, CA Clare, DK Howe, A Raedecke, J Song, Y Townsend, AR Huang, K-YA Fry, EE Mongkolsapaya, J Diamond, MS Ren, J Stuart, DI Screaton, GR |
| author_sort | Dejnirattisai, W |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:22:41Z |
| format | Journal article |
| id | oxford-uuid:1aa14da1-6df3-4660-abd6-390cd90755cf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:22:41Z |
| publishDate | 2021 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:1aa14da1-6df3-4660-abd6-390cd90755cf2022-03-26T10:56:06ZThe antigenic anatomy of SARS-CoV-2 receptor binding domainJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1aa14da1-6df3-4660-abd6-390cd90755cfEnglishSymplectic ElementsCell Press2021Dejnirattisai, WZhou, DGinn, HMDuyvesteyn, HMESpasa, DCase, JBZhao, YWalter, TSMentzer, AJLiu, CWang, BPaesen, GCSlon-Campus, JLópez-Camacho, CKafai, NMBailey, ALChen, REYing, BThompson, CBolton, JFyfe, AGupta, STan, TKGilbert-Jaramillo, JJames, WKnight, MCarroll, MWSkelly, DDold, CPeng, YLevin, RDong, TPollard, AJKnight, JCKlenerman, PTemperton, NHall, DRWilliams, MAPaterson, NGBertram, FKRSeibert, CAClare, DKHowe, ARaedecke, JSong, YTownsend, ARHuang, K-YAFry, EEMongkolsapaya, JDiamond, MSRen, JStuart, DIScreaton, GRAntibodies 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. |
| spellingShingle | Dejnirattisai, W Zhou, D Ginn, HM Duyvesteyn, HME Spasa, D Case, JB Zhao, Y Walter, TS Mentzer, AJ Liu, C Wang, B Paesen, GC Slon-Campus, J López-Camacho, C Kafai, NM Bailey, AL Chen, RE Ying, B Thompson, C Bolton, J Fyfe, A Gupta, S Tan, TK Gilbert-Jaramillo, J James, W Knight, M Carroll, MW Skelly, D Dold, C Peng, Y Levin, R Dong, T Pollard, AJ Knight, JC Klenerman, P Temperton, N Hall, DR Williams, MA Paterson, NG Bertram, FKR Seibert, CA Clare, DK Howe, A Raedecke, J Song, Y Townsend, AR Huang, K-YA Fry, EE Mongkolsapaya, J Diamond, MS Ren, J Stuart, DI Screaton, GR The antigenic anatomy of SARS-CoV-2 receptor binding domain |
| title | The antigenic anatomy of SARS-CoV-2 receptor binding domain |
| title_full | The antigenic anatomy of SARS-CoV-2 receptor binding domain |
| title_fullStr | The antigenic anatomy of SARS-CoV-2 receptor binding domain |
| title_full_unstemmed | The antigenic anatomy of SARS-CoV-2 receptor binding domain |
| title_short | The antigenic anatomy of SARS-CoV-2 receptor binding domain |
| title_sort | antigenic anatomy of sars cov 2 receptor binding domain |
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