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A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies.
Wang, Chunyan; van Haperen, Rien; Gutiérrez-Álvarez, Javier; Li, Wentao; Okba, Nisreen M A; Albulescu, Irina; Widjaja, Ivy; van Dieren, Brenda; Fernandez-Delgado, Raul; Sola, Isabel; Hurdiss, Daniel L; Daramola, Olalekan; Grosveld, Frank; van Kuppeveld, Frank J M; Haagmans, Bart L; Enjuanes, Luis; Drabek, Dubravka; Bosch, Berend-Jan.
  • Wang C; Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • van Haperen R; Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Gutiérrez-Álvarez J; Harbour BioMed, Rotterdam, the Netherlands.
  • Li W; Department of Molecular and Cell Biology, National Center for Biotechnology-Spanish National Research Council (CNB-CSIC), Madrid, Spain.
  • Okba NMA; Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Albulescu I; Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Widjaja I; Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • van Dieren B; Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Fernandez-Delgado R; Merus N.V., Utrecht, the Netherlands.
  • Sola I; Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Hurdiss DL; Department of Molecular and Cell Biology, National Center for Biotechnology-Spanish National Research Council (CNB-CSIC), Madrid, Spain.
  • Daramola O; Department of Molecular and Cell Biology, National Center for Biotechnology-Spanish National Research Council (CNB-CSIC), Madrid, Spain.
  • Grosveld F; Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • van Kuppeveld FJM; Cell Culture and Fermentation Sciences, Biopharmaceutical Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
  • Haagmans BL; Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Enjuanes L; Harbour BioMed, Rotterdam, the Netherlands.
  • Drabek D; Division of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Bosch BJ; Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
Nat Commun ; 12(1): 1715, 2021 03 17.
Article in English | MEDLINE | ID: covidwho-1139739
ABSTRACT
The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Monoclonal, Humanized / Spike Glycoprotein, Coronavirus / Betacoronavirus / Epitopes Type of study: Randomized controlled trials Topics: Vaccines Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-21968-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Monoclonal, Humanized / Spike Glycoprotein, Coronavirus / Betacoronavirus / Epitopes Type of study: Randomized controlled trials Topics: Vaccines Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-21968-w