TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85187912475&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-46443-0
DO - 10.1038/s41467-024-46443-0
M3 - Article
C2 - 38485931
AN - SCOPUS:85187912475
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2319
ER -