Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
14 Mar 2024
Historique:
received: 07 06 2023
accepted: 28 02 2024
medline: 18 3 2024
pubmed: 15 3 2024
entrez: 15 3 2024
Statut: epublish

Résumé

Monoclonal antibodies are an increasingly important tool for prophylaxis and treatment of acute virus infections like SARS-CoV-2 infection. However, their use is often restricted due to the time required for development, variable yields and high production costs, as well as the need for adaptation to newly emerging virus variants. Here we use the genetically modified filamentous fungus expression system Thermothelomyces heterothallica (C1), which has a naturally high biosynthesis capacity for secretory enzymes and other proteins, to produce a human monoclonal IgG1 antibody (HuMab 87G7) that neutralises the SARS-CoV-2 variants of concern (VOCs) Alpha, Beta, Gamma, Delta, and Omicron. Both the mammalian cell and C1 produced HuMab 87G7 broadly neutralise SARS-CoV-2 VOCs in vitro and also provide protection against VOC Omicron in hamsters. The C1 produced HuMab 87G7 is also able to protect against the Delta VOC in non-human primates. In summary, these findings show that the C1 expression system is a promising technology platform for the development of HuMabs in preventive and therapeutic medicine.

Identifiants

pubmed: 38485931
doi: 10.1038/s41467-024-46443-0
pii: 10.1038/s41467-024-46443-0
pmc: PMC10940701
doi:

Substances chimiques

Immunoglobulin G 0
Antibodies, Monoclonal 0
Antibodies, Neutralizing 0
Spike Glycoprotein, Coronavirus 0
Antibodies, Viral 0
spike protein, SARS-CoV-2 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2319

Subventions

Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 101003651

Informations de copyright

© 2024. The Author(s).

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Auteurs

Franziska K Kaiser (FK)

Research Center for Emerging Infections and Zoonosis, University of Veterinary Medicine, Foundation, Hannover, Germany.

Mariana Gonzalez Hernandez (MG)

Research Center for Emerging Infections and Zoonosis, University of Veterinary Medicine, Foundation, Hannover, Germany.

Nadine Krüger (N)

German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Ellinor Englund (E)

VTT Technical Research Centre of Finland Ltd, 02150, Espoo, Finland.

Wenjuan Du (W)

Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.

Anna Z Mykytyn (AZ)

Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.

Mathijs P Raadsen (MP)

Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.

Mart M Lamers (MM)

Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.

Francine Rodrigues Ianiski (F)

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584, CH, Utrecht, The Netherlands.

Tatiana M Shamorkina (TM)

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584, CH, Utrecht, The Netherlands.

Joost Snijder (J)

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584, CH, Utrecht, The Netherlands.

Federico Armando (F)

Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.

Georg Beythien (G)

Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.

Malgorzata Ciurkiewicz (M)

Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.

Tom Schreiner (T)

Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.

Eva Gruber-Dujardin (E)

German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Martina Bleyer (M)

German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Olga Batura (O)

German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Lena Erffmeier (L)

German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Rabea Hinkel (R)

German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Cheila Rocha (C)

German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Monica Mirolo (M)

Research Center for Emerging Infections and Zoonosis, University of Veterinary Medicine, Foundation, Hannover, Germany.

Dubravka Drabek (D)

Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands and Harbour BioMed, Rotterdam, the Netherlands.

Berend-Jan Bosch (BJ)

Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.

Mark Emalfarb (M)

Dyadic International, Inc, Jupiter, FL, USA.

Noelia Valbuena (N)

Dyadic International, Inc, Jupiter, FL, USA.

Ronen Tchelet (R)

Dyadic International, Inc, Jupiter, FL, USA.

Wolfgang Baumgärtner (W)

Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.

Markku Saloheimo (M)

VTT Technical Research Centre of Finland Ltd, 02150, Espoo, Finland.

Stefan Pöhlmann (S)

German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Frank Grosveld (F)

Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands and Harbour BioMed, Rotterdam, the Netherlands.

Bart L Haagmans (BL)

Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands. b.haagmans@erasmusmc.nl.

Albert D M E Osterhaus (ADME)

Research Center for Emerging Infections and Zoonosis, University of Veterinary Medicine, Foundation, Hannover, Germany. Albert.Osterhaus@tiho-hannover.de.
Global Virus Network, Baltimore, MD, 21201, USA. Albert.Osterhaus@tiho-hannover.de.

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Classifications MeSH