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 HinkelCheila 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*

*Corresponding author for this work

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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.

Original languageEnglish
Article number2319
JournalNature Communications
Issue number1
Publication statusPublished - 14 Mar 2024

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