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The antigenic anatomy of SARS-CoV-2 receptor binding domain.
Dejnirattisai, Wanwisa; Zhou, Daming; Ginn, Helen M; Duyvesteyn, Helen M E; Supasa, Piyada; Case, James Brett; Zhao, Yuguang; Walter, Thomas S; Mentzer, Alexander J; Liu, Chang; Wang, Beibei; Paesen, Guido C; Slon-Campos, Jose; López-Camacho, César; Kafai, Natasha M; Bailey, Adam L; Chen, Rita E; Ying, Baoling; Thompson, Craig; Bolton, Jai; Fyfe, Alex; Gupta, Sunetra; Tan, Tiong Kit; Gilbert-Jaramillo, Javier; James, William; Knight, Michael; Carroll, Miles W; Skelly, Donal; Dold, Christina; Peng, Yanchun; Levin, Robert; Dong, Tao; Pollard, Andrew J; Knight, Julian C; Klenerman, Paul; Temperton, Nigel; Hall, David R; Williams, Mark A; Paterson, Neil G; Bertram, Felicity K R; Siebert, C Alistair; Clare, Daniel K; Howe, Andrew; Radecke, Julika; Song, Yun; Townsend, Alain R; Huang, Kuan-Ying A; Fry, Elizabeth E; Mongkolsapaya, Juthathip; Diamond, Michael S.
  • Dejnirattisai W; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
  • Zhou D; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford OX3 7BN, UK.
  • Ginn HM; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Duyvesteyn HME; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford OX3 7BN, UK.
  • Supasa P; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
  • Case JB; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Zhao Y; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford OX3 7BN, UK.
  • Walter TS; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford OX3 7BN, UK.
  • Mentzer AJ; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Liu C; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  • Wang B; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
  • Paesen GC; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford OX3 7BN, UK.
  • Slon-Campos J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
  • López-Camacho C; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
  • Kafai NM; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Bailey AL; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Chen RE; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Ying B; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Thompson C; Peter Medawar Building for Pathogen Research, Oxford OX1 3SY, UK; Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK.
  • Bolton J; Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK.
  • Fyfe A; Peter Medawar Building for Pathogen Research, Oxford OX1 3SY, UK; Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK.
  • Gupta S; Peter Medawar Building for Pathogen Research, Oxford OX1 3SY, UK; Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK.
  • Tan TK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • Gilbert-Jaramillo J; Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
  • James W; Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
  • Knight M; Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
  • Carroll MW; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; National Infection Service, Public Health England (PHE), Porton Down, Salisbury SP4 0JG, UK.
  • Skelly D; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
  • Dold C; Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Oxford OX3 7LE, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK.
  • Peng Y; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • Levin R; Worthing Hospital, Worthing BN11 2DH, UK.
  • Dong T; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Medicine, Universi
  • Pollard AJ; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Department of Paediatrics, Oxford Vaccine Group, University of Oxford, Oxford OX3 7LE, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK.
  • Knight JC; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Klenerman P; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford OX1 3SY, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK; Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
  • Temperton N; Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK.
  • Hall DR; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Williams MA; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Paterson NG; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Bertram FKR; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Siebert CA; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Clare DK; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Howe A; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Radecke J; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Song Y; Diamond Light Source Ltd, Harwell Science & Innovation Campus, Didcot OX11 0DE, UK.
  • Townsend AR; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • Huang KA; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Fry EE; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford OX3 7BN, UK.
  • Mongkolsapaya J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK; Siriraj Center of Research Excellence in Dengue & Emerging Pathogens, Dean Of
  • Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine
Cell ; 184(8): 2183-2200.e22, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1086819
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / COVID-19 / Antibodies, Monoclonal / Antibodies, Viral Limits: Animals / Female / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.02.032

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / COVID-19 / Antibodies, Monoclonal / Antibodies, Viral Limits: Animals / Female / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.02.032