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 () and Albert D.M.E. Osterhaus ()
Additional contact information
Franziska K. Kaiser: University of Veterinary Medicine, Foundation
Mariana Gonzalez Hernandez: 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: Utrecht University
Anna Z. Mykytyn: Erasmus Medical Center
Mathijs P. Raadsen: Erasmus Medical Center
Mart M. Lamers: Erasmus Medical Center
Francine Rodrigues Ianiski: Utrecht University
Tatiana M. Shamorkina: Utrecht University
Joost Snijder: Utrecht University
Federico Armando: University of Veterinary Medicine, Foundation
Georg Beythien: University of Veterinary Medicine, Foundation
Malgorzata Ciurkiewicz: University of Veterinary Medicine, Foundation
Tom Schreiner: 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: University of Veterinary Medicine, Foundation
Dubravka Drabek: Rotterdam, the Netherlands and Harbour BioMed
Berend-Jan Bosch: Utrecht University
Mark Emalfarb: Inc
Noelia Valbuena: Inc
Ronen Tchelet: Inc
Wolfgang Baumgärtner: 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: Rotterdam, the Netherlands and Harbour BioMed
Bart L. Haagmans: Erasmus Medical Center
Albert D.M.E. Osterhaus: University of Veterinary Medicine, Foundation

Nature Communications, 2024, vol. 15, issue 1, 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.

Date: 2024
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DOI: 10.1038/s41467-024-46443-0

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