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Enhanced fitness of SARS-CoV-2 variant of concern B.1.1.7, but not B.1.351, in animal models

View ORCID ProfileLorenz Ulrich, View ORCID ProfileNico Joel Halwe, View ORCID ProfileAdriano Taddeo, Nadine Ebert, View ORCID ProfileJacob Schön, Christelle Devisme, Bettina Salome Trüeb, View ORCID ProfileBernd Hoffmann, Manon Wider, View ORCID ProfileMeriem Bekliz, Manel Essaidi-Laziosi, Marie Luisa Schmidt, Daniela Niemeyer, View ORCID ProfileVictor Max Corman, View ORCID ProfileAnna Kraft, Aurélie Godel, Laura Laloli, View ORCID ProfileJenna N. Kelly, View ORCID ProfileAngele Breithaupt, View ORCID ProfileClaudia Wylezich, Inês Berenguer Veiga, Mitra Gultom, View ORCID ProfileKenneth Adea, View ORCID ProfileBenjamin Meyer, Christiane Eberhardt, View ORCID ProfileLisa Thomann, Monika Gsell-Albert, View ORCID ProfileFabien Labroussaa, View ORCID ProfileJörg Jores, View ORCID ProfileArtur Summerfield, View ORCID ProfileChristian Drosten, View ORCID ProfileIsabella Anne Eckerle, View ORCID ProfileRonald Dijkman, View ORCID ProfileDonata Hoffmann, View ORCID ProfileVolker Thiel, View ORCID ProfileMartin Beer, View ORCID ProfileCharaf Benarafa
doi: https://doi.org/10.1101/2021.06.28.450190
Lorenz Ulrich
1Institute of Diagnostic Virology, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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Nico Joel Halwe
1Institute of Diagnostic Virology, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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Adriano Taddeo
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Nadine Ebert
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Jacob Schön
1Institute of Diagnostic Virology, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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Christelle Devisme
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Bettina Salome Trüeb
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
4Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Bernd Hoffmann
1Institute of Diagnostic Virology, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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Manon Wider
5Institute for Infectious Diseases, University of Bern; Bern, Switzerland
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Meriem Bekliz
6Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva; Geneva, Switzerland
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  • ORCID record for Meriem Bekliz
Manel Essaidi-Laziosi
6Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva; Geneva, Switzerland
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Marie Luisa Schmidt
7Charité – Universitätsmedizin Berlin, Institute of Virology; Berlin, Germany
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Daniela Niemeyer
7Charité – Universitätsmedizin Berlin, Institute of Virology; Berlin, Germany
8German Centre for Infection Research (DZIF), associated partner site Charité; Berlin, Germany
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Victor Max Corman
7Charité – Universitätsmedizin Berlin, Institute of Virology; Berlin, Germany
8German Centre for Infection Research (DZIF), associated partner site Charité; Berlin, Germany
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Anna Kraft
1Institute of Diagnostic Virology, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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Aurélie Godel
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Laura Laloli
5Institute for Infectious Diseases, University of Bern; Bern, Switzerland
9Graduate School for Biomedical Science, University of Bern, Bern, Switzerland
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Jenna N. Kelly
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Angele Breithaupt
10Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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Claudia Wylezich
1Institute of Diagnostic Virology, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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Inês Berenguer Veiga
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Mitra Gultom
5Institute for Infectious Diseases, University of Bern; Bern, Switzerland
9Graduate School for Biomedical Science, University of Bern, Bern, Switzerland
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Kenneth Adea
6Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva; Geneva, Switzerland
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Benjamin Meyer
11Centre for Vaccinology, Department of Pathology and Immunology, University of Geneva; Geneva, Switzerland
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Christiane Eberhardt
11Centre for Vaccinology, Department of Pathology and Immunology, University of Geneva; Geneva, Switzerland
12Division of General Paediatrics, Department of Woman, Child and Adolescent Medicine, Faculty of Medicine, University of Geneva; Geneva, Switzerland
13Emory Vaccine Center, Emory University; Atlanta, Georgia, USA
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Lisa Thomann
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Monika Gsell-Albert
5Institute for Infectious Diseases, University of Bern; Bern, Switzerland
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Fabien Labroussaa
4Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Jörg Jores
4Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Artur Summerfield
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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Christian Drosten
7Charité – Universitätsmedizin Berlin, Institute of Virology; Berlin, Germany
8German Centre for Infection Research (DZIF), associated partner site Charité; Berlin, Germany
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Isabella Anne Eckerle
6Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva; Geneva, Switzerland
14Division of Infectious Disease, Geneva University Hospitals; Geneva, Switzerland
15Division of Laboratory Medicine, Laboratory of Virology, Geneva University Hospitals; Geneva, Switzerland
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Ronald Dijkman
5Institute for Infectious Diseases, University of Bern; Bern, Switzerland
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Donata Hoffmann
1Institute of Diagnostic Virology, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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Volker Thiel
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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  • For correspondence: charaf.benarafa@vetsuisse.unibe.ch volker.thiel@vetsuisse.unibe.ch martin.beer@fli.de
Martin Beer
1Institute of Diagnostic Virology, Friedrich-Loeffler-Institut; Greifswald-Insel Riems, Germany
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  • For correspondence: charaf.benarafa@vetsuisse.unibe.ch volker.thiel@vetsuisse.unibe.ch martin.beer@fli.de
Charaf Benarafa
2Institute of Virology and Immunology (IVI); Mittelhäusern, Switzerland
3Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern; Bern, Switzerland
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  • For correspondence: charaf.benarafa@vetsuisse.unibe.ch volker.thiel@vetsuisse.unibe.ch martin.beer@fli.de
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Abstract

Emerging variants of concern (VOCs) drive the SARS-CoV-2 pandemic. We assessed VOC B.1.1.7, now prevalent in several countries, and VOC B.1.351, representing the greatest threat to populations with immunity to the early SARS-CoV-2 progenitors. B.1.1.7 showed a clear fitness advantage over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in the spike glycoprotein were major drivers for fitness advantage. In the “superspreader” hamster model, B.1.1.7 and wt-S614G had comparable fitness, whereas B.1.351 was outcompeted. The VOCs had similar replication kinetics as compared to wt-S614G in human airway epithelial cultures. Our study highlights the importance of using multiple models for complete fitness characterization of VOCs and demonstrates adaptation of B.1.1.7 towards increased upper respiratory tract replication and enhanced transmission in vivo.

Summary sentence B.1.1.7 VOC outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 28, 2021.
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Enhanced fitness of SARS-CoV-2 variant of concern B.1.1.7, but not B.1.351, in animal models
Lorenz Ulrich, Nico Joel Halwe, Adriano Taddeo, Nadine Ebert, Jacob Schön, Christelle Devisme, Bettina Salome Trüeb, Bernd Hoffmann, Manon Wider, Meriem Bekliz, Manel Essaidi-Laziosi, Marie Luisa Schmidt, Daniela Niemeyer, Victor Max Corman, Anna Kraft, Aurélie Godel, Laura Laloli, Jenna N. Kelly, Angele Breithaupt, Claudia Wylezich, Inês Berenguer Veiga, Mitra Gultom, Kenneth Adea, Benjamin Meyer, Christiane Eberhardt, Lisa Thomann, Monika Gsell-Albert, Fabien Labroussaa, Jörg Jores, Artur Summerfield, Christian Drosten, Isabella Anne Eckerle, Ronald Dijkman, Donata Hoffmann, Volker Thiel, Martin Beer, Charaf Benarafa
bioRxiv 2021.06.28.450190; doi: https://doi.org/10.1101/2021.06.28.450190
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Enhanced fitness of SARS-CoV-2 variant of concern B.1.1.7, but not B.1.351, in animal models
Lorenz Ulrich, Nico Joel Halwe, Adriano Taddeo, Nadine Ebert, Jacob Schön, Christelle Devisme, Bettina Salome Trüeb, Bernd Hoffmann, Manon Wider, Meriem Bekliz, Manel Essaidi-Laziosi, Marie Luisa Schmidt, Daniela Niemeyer, Victor Max Corman, Anna Kraft, Aurélie Godel, Laura Laloli, Jenna N. Kelly, Angele Breithaupt, Claudia Wylezich, Inês Berenguer Veiga, Mitra Gultom, Kenneth Adea, Benjamin Meyer, Christiane Eberhardt, Lisa Thomann, Monika Gsell-Albert, Fabien Labroussaa, Jörg Jores, Artur Summerfield, Christian Drosten, Isabella Anne Eckerle, Ronald Dijkman, Donata Hoffmann, Volker Thiel, Martin Beer, Charaf Benarafa
bioRxiv 2021.06.28.450190; doi: https://doi.org/10.1101/2021.06.28.450190

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