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

doi:10.1038/s41467-024-46443-0

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

Research output: Contribution to journal › Article › Scientific › peer-review

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.

Original language	English
Article number	2319
Number of pages	14
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-46443-0
Publication status	Published - 14 Mar 2024
MoE publication type	A1 Journal article-refereed

Funding

Part of the work was funded by the MANCO project, a European Union’s Horizon 2020 research and innovation program (grant agreement No 101003651, D.D., B.J.B., F.G., B.L.H., A.O.). The study was also supported by the COVID-19 Research Network of the State of Lower Saxony (COFONI) with funding from the Ministry of Science and Culture of Lower Saxony, Germany (14–76403–184, F.A., M.C., W.B.). This research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation, G.B., L.H., F.K., W.B., and A.O.) -398066876/GRK 2485/1-VIPER-GRK. S.P. acknowledges funding by BMBF (01KI2006D, 01KI20328A, 01KX2021), the Ministry for Science and Culture of Lower Saxony (14-76103-184, COFONI Network, including projects 7FF22, 6FF22, 10FF22), and the German Research Foundation (DFG; PO 716/11-1, PO 716/14-1). J.S. is funded by the Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI; 024.002.009). T.S. was supported by the Luxemburgish National Research Fund (FNR, Project Reference: 15686728). This open access publication was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)- 491094227 “Open Access Publication Funding” and “the University of Veterinary Medicine Hannover, Foundation.”

Keywords

Animals
Cricetinae
Humans
SARS-CoV-2/genetics
COVID-19/prevention & control
Primates
Immunoglobulin G
Antibodies, Monoclonal
Fungi
Antibodies, Neutralizing
Spike Glycoprotein, Coronavirus
Antibodies, Viral
Mammals

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Kaiser, F. K., Hernandez, M. G., Krüger, N., Englund, E., Du, W., Mykytyn, A. Z., Raadsen, M. P., Lamers, M. M., Rodrigues Ianiski, F., Shamorkina, T. M., Snijder, J., Armando, F., Beythien, G., Ciurkiewicz, M., Schreiner, T., Gruber-Dujardin, E., Bleyer, M., Batura, O., Erffmeier, L., ... Osterhaus, A. D. M. E. (2024). Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models. Nature Communications, 15(1), Article 2319. https://doi.org/10.1038/s41467-024-46443-0

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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.",

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Kaiser, FK, Hernandez, MG, Krüger, N, Englund, E, Du, W, Mykytyn, AZ, Raadsen, MP, Lamers, MM, Rodrigues Ianiski, F, Shamorkina, TM, Snijder, J, Armando, F, Beythien, G, Ciurkiewicz, M, Schreiner, T, Gruber-Dujardin, E, Bleyer, M, Batura, O, Erffmeier, L, Hinkel, R, Rocha, C, Mirolo, M, Drabek, D, Bosch, BJ, Emalfarb, M, Valbuena, N, Tchelet, R, Baumgärtner, W, Saloheimo, M, Pöhlmann, S, Grosveld, F, Haagmans, BL & Osterhaus, ADME 2024, 'Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models', Nature Communications, vol. 15, no. 1, 2319. https://doi.org/10.1038/s41467-024-46443-0

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T1 - Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models

AU - Kaiser, Franziska K.

AU - Hernandez, Mariana Gonzalez

AU - Krüger, Nadine

AU - Englund, Ellinor

AU - Du, Wenjuan

AU - Mykytyn, Anna Z.

AU - Raadsen, Mathijs P.

AU - Lamers, Mart M.

AU - Rodrigues Ianiski, Francine

AU - Shamorkina, Tatiana M.

AU - Snijder, Joost

AU - Armando, Federico

AU - Beythien, Georg

AU - Ciurkiewicz, Malgorzata

AU - Schreiner, Tom

AU - Gruber-Dujardin, Eva

AU - Bleyer, Martina

AU - Batura, Olga

AU - Erffmeier, Lena

AU - Hinkel, Rabea

AU - Rocha, Cheila

AU - Mirolo, Monica

AU - Drabek, Dubravka

AU - Bosch, Berend Jan

AU - Emalfarb, Mark

AU - Valbuena, Noelia

AU - Tchelet, Ronen

AU - Baumgärtner, Wolfgang

AU - Saloheimo, Markku

AU - Pöhlmann, Stefan

AU - Grosveld, Frank

AU - Haagmans, Bart L.

AU - Osterhaus, Albert D.M.E.

PY - 2024/3/14

Y1 - 2024/3/14

N2 - 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.

AB - 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.

KW - Animals

KW - Cricetinae

KW - Humans

KW - SARS-CoV-2/genetics

KW - COVID-19/prevention & control

KW - Primates

KW - Immunoglobulin G

KW - Antibodies, Monoclonal

KW - Fungi

KW - Antibodies, Neutralizing

KW - Spike Glycoprotein, Coronavirus

KW - Antibodies, Viral

KW - Mammals

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U2 - 10.1038/s41467-024-46443-0

DO - 10.1038/s41467-024-46443-0

M3 - Article

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AN - SCOPUS:85187912475

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2319

ER -

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

Abstract

Funding

Keywords

UN SDGs

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