Nature Communications (Mar 2024)
Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models
- Franziska K. Kaiser,
- Mariana Gonzalez Hernandez,
- Nadine Krüger,
- Ellinor Englund,
- Wenjuan Du,
- Anna Z. Mykytyn,
- Mathijs P. Raadsen,
- Mart M. Lamers,
- Francine Rodrigues Ianiski,
- Tatiana M. Shamorkina,
- Joost Snijder,
- Federico Armando,
- Georg Beythien,
- Malgorzata Ciurkiewicz,
- Tom Schreiner,
- Eva Gruber-Dujardin,
- Martina Bleyer,
- Olga Batura,
- Lena Erffmeier,
- Rabea Hinkel,
- Cheila Rocha,
- Monica Mirolo,
- Dubravka Drabek,
- Berend-Jan Bosch,
- Mark Emalfarb,
- Noelia Valbuena,
- Ronen Tchelet,
- Wolfgang Baumgärtner,
- Markku Saloheimo,
- Stefan Pöhlmann,
- Frank Grosveld,
- Bart L. Haagmans,
- Albert D.M.E. Osterhaus
Affiliations
- Franziska K. Kaiser
- Research Center for Emerging Infections and Zoonosis, University of Veterinary Medicine, Foundation
- Mariana Gonzalez Hernandez
- Research Center for Emerging Infections and Zoonosis, University of Veterinary Medicine, Foundation
- Nadine Krüger
- German Primate Center - Leibniz Institute for Primate Research
- Ellinor Englund
- VTT Technical Research Centre of Finland Ltd
- Wenjuan Du
- Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University
- Anna Z. Mykytyn
- Department of Viroscience, Erasmus Medical Center
- Mathijs P. Raadsen
- Department of Viroscience, Erasmus Medical Center
- Mart M. Lamers
- Department of Viroscience, Erasmus Medical Center
- Francine Rodrigues Ianiski
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University
- Tatiana M. Shamorkina
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University
- Joost Snijder
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University
- Federico Armando
- Department of Pathology, University of Veterinary Medicine, Foundation
- Georg Beythien
- Department of Pathology, University of Veterinary Medicine, Foundation
- Malgorzata Ciurkiewicz
- Department of Pathology, University of Veterinary Medicine, Foundation
- Tom Schreiner
- Department of Pathology, University of Veterinary Medicine, Foundation
- Eva Gruber-Dujardin
- German Primate Center - Leibniz Institute for Primate Research
- Martina Bleyer
- German Primate Center - Leibniz Institute for Primate Research
- Olga Batura
- German Primate Center - Leibniz Institute for Primate Research
- Lena Erffmeier
- German Primate Center - Leibniz Institute for Primate Research
- Rabea Hinkel
- German Primate Center - Leibniz Institute for Primate Research
- Cheila Rocha
- German Primate Center - Leibniz Institute for Primate Research
- Monica Mirolo
- Research Center for Emerging Infections and Zoonosis, University of Veterinary Medicine, Foundation
- Dubravka Drabek
- Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands and Harbour BioMed
- Berend-Jan Bosch
- Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University
- Mark Emalfarb
- Dyadic International, Inc
- Noelia Valbuena
- Dyadic International, Inc
- Ronen Tchelet
- Dyadic International, Inc
- Wolfgang Baumgärtner
- Department of Pathology, University of Veterinary Medicine, Foundation
- Markku Saloheimo
- VTT Technical Research Centre of Finland Ltd
- Stefan Pöhlmann
- German Primate Center - Leibniz Institute for Primate Research
- Frank Grosveld
- Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands and Harbour BioMed
- Bart L. Haagmans
- Department of Viroscience, Erasmus Medical Center
- Albert D.M.E. Osterhaus
- Research Center for Emerging Infections and Zoonosis, University of Veterinary Medicine, Foundation
- DOI
- https://doi.org/10.1038/s41467-024-46443-0
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 14
Abstract
Abstract 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.
