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Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model

View ORCID ProfileMaya Imbrechts, Wim Maes, Louanne Ampofo, Nathalie Van den Berghe, Bas Calcoen, Dominique Van Looveren, Sam Noppen, Kevin Hollevoet, Thomas Vercruysse, Xin Zhang, View ORCID ProfileRana Abdelnabi, Caroline Foo, Hendrik Jan Thibaut, View ORCID ProfileDirk Jochmans, Karen Ven, Jeroen Lammertyn, Karen Vanhoorelbeke, Nico Callewaert, Paul De Munter, Dominique Schols, Johan Neyts, Paul Declerck, Nick Geukens
doi: https://doi.org/10.1101/2021.11.25.470011
Maya Imbrechts
1KU Leuven, PharmAbs: the KU Leuven Antibody Center, B-3000 Leuven, Belgium
2KU Leuven, Department Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, B-3000 Leuven, Belgium
3KU Leuven, MabMine: KU Leuven single B cell mining platform, B-3000 Leuven, Belgium
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  • For correspondence: nick.geukens@kuleuven.be
Wim Maes
1KU Leuven, PharmAbs: the KU Leuven Antibody Center, B-3000 Leuven, Belgium
3KU Leuven, MabMine: KU Leuven single B cell mining platform, B-3000 Leuven, Belgium
4KU Leuven Campus Kortrijk, IRF Life Sciences, Laboratory for Thrombosis Research, B-3000 Leuven, Belgium
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Louanne Ampofo
1KU Leuven, PharmAbs: the KU Leuven Antibody Center, B-3000 Leuven, Belgium
3KU Leuven, MabMine: KU Leuven single B cell mining platform, B-3000 Leuven, Belgium
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Nathalie Van den Berghe
2KU Leuven, Department Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, B-3000 Leuven, Belgium
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Bas Calcoen
4KU Leuven Campus Kortrijk, IRF Life Sciences, Laboratory for Thrombosis Research, B-3000 Leuven, Belgium
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Dominique Van Looveren
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
6Molecular Vaccinology and Vaccine Discovery, Belgium
7Translational Platform Virology and Chemotherapy (TPVC)
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Sam Noppen
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
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Kevin Hollevoet
1KU Leuven, PharmAbs: the KU Leuven Antibody Center, B-3000 Leuven, Belgium
2KU Leuven, Department Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, B-3000 Leuven, Belgium
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Thomas Vercruysse
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
6Molecular Vaccinology and Vaccine Discovery, Belgium
7Translational Platform Virology and Chemotherapy (TPVC)
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Xin Zhang
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
8GVN, global virus network
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Rana Abdelnabi
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
8GVN, global virus network
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Caroline Foo
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
8GVN, global virus network
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Hendrik Jan Thibaut
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
6Molecular Vaccinology and Vaccine Discovery, Belgium
7Translational Platform Virology and Chemotherapy (TPVC)
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Dirk Jochmans
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
8GVN, global virus network
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Karen Ven
3KU Leuven, MabMine: KU Leuven single B cell mining platform, B-3000 Leuven, Belgium
9KU Leuven, Department of Biosystems, Biosensors Group, B-3000 Leuven, Belgium
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Jeroen Lammertyn
3KU Leuven, MabMine: KU Leuven single B cell mining platform, B-3000 Leuven, Belgium
9KU Leuven, Department of Biosystems, Biosensors Group, B-3000 Leuven, Belgium
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Karen Vanhoorelbeke
1KU Leuven, PharmAbs: the KU Leuven Antibody Center, B-3000 Leuven, Belgium
3KU Leuven, MabMine: KU Leuven single B cell mining platform, B-3000 Leuven, Belgium
4KU Leuven Campus Kortrijk, IRF Life Sciences, Laboratory for Thrombosis Research, B-3000 Leuven, Belgium
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Nico Callewaert
10AZ Groeninge Hospital Clinical Laboratory, B-8500 Kortrijk, Belgium
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Paul De Munter
11Department of Internal Medicine, University Hospitals Leuven, B-3000 Leuven, Belgium
12KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory for Clinical Infectious and Inflammatory Disorders, B-3000 Leuven, Belgium
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Dominique Schols
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
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Johan Neyts
5KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
6Molecular Vaccinology and Vaccine Discovery, Belgium
8GVN, global virus network
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Paul Declerck
1KU Leuven, PharmAbs: the KU Leuven Antibody Center, B-3000 Leuven, Belgium
2KU Leuven, Department Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, B-3000 Leuven, Belgium
3KU Leuven, MabMine: KU Leuven single B cell mining platform, B-3000 Leuven, Belgium
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Nick Geukens
1KU Leuven, PharmAbs: the KU Leuven Antibody Center, B-3000 Leuven, Belgium
3KU Leuven, MabMine: KU Leuven single B cell mining platform, B-3000 Leuven, Belgium
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  • For correspondence: nick.geukens@kuleuven.be
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Abstract

Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants can escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent COVID-19 patient, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 Wuhan, alpha, beta, gamma and delta infection in vitro. In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 μg/ml, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 29, 2021.
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Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model
Maya Imbrechts, Wim Maes, Louanne Ampofo, Nathalie Van den Berghe, Bas Calcoen, Dominique Van Looveren, Sam Noppen, Kevin Hollevoet, Thomas Vercruysse, Xin Zhang, Rana Abdelnabi, Caroline Foo, Hendrik Jan Thibaut, Dirk Jochmans, Karen Ven, Jeroen Lammertyn, Karen Vanhoorelbeke, Nico Callewaert, Paul De Munter, Dominique Schols, Johan Neyts, Paul Declerck, Nick Geukens
bioRxiv 2021.11.25.470011; doi: https://doi.org/10.1101/2021.11.25.470011
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Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model
Maya Imbrechts, Wim Maes, Louanne Ampofo, Nathalie Van den Berghe, Bas Calcoen, Dominique Van Looveren, Sam Noppen, Kevin Hollevoet, Thomas Vercruysse, Xin Zhang, Rana Abdelnabi, Caroline Foo, Hendrik Jan Thibaut, Dirk Jochmans, Karen Ven, Jeroen Lammertyn, Karen Vanhoorelbeke, Nico Callewaert, Paul De Munter, Dominique Schols, Johan Neyts, Paul Declerck, Nick Geukens
bioRxiv 2021.11.25.470011; doi: https://doi.org/10.1101/2021.11.25.470011

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