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A neutralizing epitope on the SD1 domain of SARS-CoV-2 spike targeted following infection and vaccination.
Seow, Jeffrey; Khan, Hataf; Rosa, Annachiara; Calvaresi, Valeria; Graham, Carl; Pickering, Suzanne; Pye, Valerie E; Cronin, Nora B; Huettner, Isabella; Malim, Michael H; Politis, Argyris; Cherepanov, Peter; Doores, Katie J.
  • Seow J; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK.
  • Khan H; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK.
  • Rosa A; Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.
  • Calvaresi V; Department of Chemistry, King's College London, London, UK.
  • Graham C; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK.
  • Pickering S; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK.
  • Pye VE; Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.
  • Cronin NB; LonCEM Facility, The Francis Crick Institute, London, UK.
  • Huettner I; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK.
  • Malim MH; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK.
  • Politis A; Department of Chemistry, King's College London, London, UK. Electronic address: argyris.politis@kcl.ac.uk.
  • Cherepanov P; Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK; Department of Infectious Disease, St-Mary's Campus, Imperial College London, London, UK. Electronic address: peter.cherepanov@crick.ac.uk.
  • Doores KJ; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK. Electronic address: katie.doores@kcl.ac.uk.
Cell Rep ; 40(8): 111276, 2022 08 23.
Article in English | MEDLINE | ID: covidwho-1982702
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the target for neutralizing antibodies elicited following both infection and vaccination. While extensive research has shown that the receptor binding domain (RBD) and, to a lesser extent, the N-terminal domain (NTD) are the predominant targets for neutralizing antibodies, identification of neutralizing epitopes beyond these regions is important for informing vaccine development and understanding antibody-mediated immune escape. Here, we identify a class of broadly neutralizing antibodies that bind an epitope on the spike subdomain 1 (SD1) and that have arisen from infection or vaccination. Using cryo-electron microscopy (cryo-EM) and hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), we show that SD1-specific antibody P008_60 binds an epitope that is not accessible within the canonical prefusion states of the SARS-CoV-2 spike, suggesting a transient conformation of the viral glycoprotein that is vulnerable to neutralization.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.111276

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.111276