Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models
© 2024. The Author(s)..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
---|---|
Enthalten in: |
Nature communications - 15(2024), 1 vom: 14. März, Seite 2319 |
Sprache: |
Englisch |
---|
Links: |
---|
Themen: |
Antibodies, Monoclonal |
---|
Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.1038/s41467-024-46443-0 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM369756177 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM369756177 | ||
003 | DE-627 | ||
005 | 20240318234803.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240315s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1038/s41467-024-46443-0 |2 doi | |
028 | 5 | 2 | |a pubmed24n1335.xml |
035 | |a (DE-627)NLM369756177 | ||
035 | |a (NLM)38485931 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Kaiser, Franziska K |e verfasserin |4 aut | |
245 | 1 | 0 | |a Filamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 18.03.2024 | ||
500 | |a Date Revised 18.03.2024 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2024. The Author(s). | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 7 | |a Immunoglobulin G |2 NLM | |
650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
650 | 7 | |a Antibodies, Viral |2 NLM | |
650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
700 | 1 | |a Hernandez, Mariana Gonzalez |e verfasserin |4 aut | |
700 | 1 | |a Krüger, Nadine |e verfasserin |4 aut | |
700 | 1 | |a Englund, Ellinor |e verfasserin |4 aut | |
700 | 1 | |a Du, Wenjuan |e verfasserin |4 aut | |
700 | 1 | |a Mykytyn, Anna Z |e verfasserin |4 aut | |
700 | 1 | |a Raadsen, Mathijs P |e verfasserin |4 aut | |
700 | 1 | |a Lamers, Mart M |e verfasserin |4 aut | |
700 | 1 | |a Rodrigues Ianiski, Francine |e verfasserin |4 aut | |
700 | 1 | |a Shamorkina, Tatiana M |e verfasserin |4 aut | |
700 | 1 | |a Snijder, Joost |e verfasserin |4 aut | |
700 | 1 | |a Armando, Federico |e verfasserin |4 aut | |
700 | 1 | |a Beythien, Georg |e verfasserin |4 aut | |
700 | 1 | |a Ciurkiewicz, Malgorzata |e verfasserin |4 aut | |
700 | 1 | |a Schreiner, Tom |e verfasserin |4 aut | |
700 | 1 | |a Gruber-Dujardin, Eva |e verfasserin |4 aut | |
700 | 1 | |a Bleyer, Martina |e verfasserin |4 aut | |
700 | 1 | |a Batura, Olga |e verfasserin |4 aut | |
700 | 1 | |a Erffmeier, Lena |e verfasserin |4 aut | |
700 | 1 | |a Hinkel, Rabea |e verfasserin |4 aut | |
700 | 1 | |a Rocha, Cheila |e verfasserin |4 aut | |
700 | 1 | |a Mirolo, Monica |e verfasserin |4 aut | |
700 | 1 | |a Drabek, Dubravka |e verfasserin |4 aut | |
700 | 1 | |a Bosch, Berend-Jan |e verfasserin |4 aut | |
700 | 1 | |a Emalfarb, Mark |e verfasserin |4 aut | |
700 | 1 | |a Valbuena, Noelia |e verfasserin |4 aut | |
700 | 1 | |a Tchelet, Ronen |e verfasserin |4 aut | |
700 | 1 | |a Baumgärtner, Wolfgang |e verfasserin |4 aut | |
700 | 1 | |a Saloheimo, Markku |e verfasserin |4 aut | |
700 | 1 | |a Pöhlmann, Stefan |e verfasserin |4 aut | |
700 | 1 | |a Grosveld, Frank |e verfasserin |4 aut | |
700 | 1 | |a Haagmans, Bart L |e verfasserin |4 aut | |
700 | 1 | |a Osterhaus, Albert D M E |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 15(2024), 1 vom: 14. März, Seite 2319 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
773 | 1 | 8 | |g volume:15 |g year:2024 |g number:1 |g day:14 |g month:03 |g pages:2319 |
856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-024-46443-0 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 15 |j 2024 |e 1 |b 14 |c 03 |h 2319 |