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Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers.
Vanshylla, Kanika; Fan, Chengcheng; Wunsch, Marie; Poopalasingam, Nareshkumar; Meijers, Matthijs; Kreer, Christoph; Kleipass, Franziska; Ruchnewitz, Denis; Ercanoglu, Meryem S; Gruell, Henning; Münn, Friederike; Pohl, Kai; Janicki, Hanna; Nolden, Tobias; Bartl, Simone; Stein, Saskia C; Augustin, Max; Dewald, Felix; Gieselmann, Lutz; Schommers, Philipp; Schulz, Thomas F; Sander, Leif Erik; Koch, Manuel; Luksza, Marta; Lässig, Michael; Bjorkman, Pamela J; Klein, Florian.
  • Vanshylla K; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Fan C; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Wunsch M; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Poopalasingam N; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Meijers M; Institute for Biological Physics, University of Cologne, 50937 Cologne, Germany.
  • Kreer C; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Kleipass F; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Ruchnewitz D; Institute for Biological Physics, University of Cologne, 50937 Cologne, Germany.
  • Ercanoglu MS; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Gruell H; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Münn F; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, 13353 Berlin, Germany.
  • Pohl K; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, 13353 Berlin, Germany.
  • Janicki H; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Nolden T; Vira Therapeutics GmbH, 6063 Rum, Austria.
  • Bartl S; Vira Therapeutics GmbH, 6063 Rum, Austria; Boehringer Ingelheim International GmbH, Ingelheim, Germany.
  • Stein SC; Institute of Virology, Hannover Medical School, Hannover, Germany.
  • Augustin M; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
  • Dewald F; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Gieselmann L; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Schommers P; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany.
  • Schulz TF; Institute of Virology, Hannover Medical School, Hannover, Germany.
  • Sander LE; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Berlin, 13353 Berlin, Germany.
  • Koch M; Institute for Dental Research and Oral Musculoskeletal Biology and Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
  • Luksza M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lässig M; Institute for Biological Physics, University of Cologne, 50937 Cologne, Germany.
  • Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Klein F; Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germ
Cell Host Microbe ; 30(1): 69-82.e10, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1638702
ABSTRACT
A fraction of COVID-19 convalescent individuals mount a potent antibody response to SARS-CoV-2 with cross-reactivity to SARS-CoV-1. To uncover their humoral response in detail, we performed single B cell analysis from 10 SARS-CoV-2 elite neutralizers. We isolated and analyzed 126 monoclonal antibodies, many of which were sarbecovirus cross-reactive, with some displaying merbecovirus- and embecovirus-reactivity. Several isolated broadly neutralizing antibodies were effective against B.1.1.7, B.1.351, B.1.429, B.1.617, and B.1.617.2 variants and 19 prominent potential escape sites. Furthermore, assembly of 716,806 SARS-CoV-2 sequences predicted emerging escape variants, which were also effectively neutralized. One of these broadly neutralizing potent antibodies, R40-1G8, is a IGHV3-53 RBD-class-1 antibody. Remarkably, cryo-EM analysis revealed that R40-1G8 has a flexible binding mode, targeting both "up" and "down" conformations of the RBD. Given the threat of emerging SARS-CoV-2 variants, we demonstrate that elite neutralizers are a valuable source for isolating ultrapotent antibody candidates to prevent and treat SARS-CoV-2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Broadly Neutralizing Antibodies / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Animals / Female / Humans / Male / Middle aged Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2022 Document Type: Article Affiliation country: J.chom.2021.12.010

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Broadly Neutralizing Antibodies / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Animals / Female / Humans / Male / Middle aged Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2022 Document Type: Article Affiliation country: J.chom.2021.12.010