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TitlePlant-produced SARS-CoV-2 antibody engineered towards enhanced potency and in vivo efficacy.
Journal, issue, pagesPlant Biotechnol J, Vol. 23, Issue 1, Page 4-16, Year 2025
Publish dateNov 19, 2024
AuthorsSteven W de Taeye / Loïc Faye / Bertrand Morel / Angela I Schriek / Jeffrey C Umotoy / Meng Yuan / Natalia A Kuzmina / Hannah L Turner / Xueyong Zhu / Clemens Grünwald-Gruber / Meliawati Poniman / Judith A Burger / Tom G Caniels / Anne-Catherine Fitchette / Réjean Desgagnés / Virginie Stordeur / Lucie Mirande / Guillaume Beauverger / Godelieve de Bree / Gabriel Ozorowski / Andrew B Ward / Ian A Wilson / Alexander Bukreyev / Rogier W Sanders / Louis-Philippe Vezina / Tim Beaumont / Marit J van Gils / Véronique Gomord /
PubMed AbstractPrevention of severe COVID-19 disease by SARS-CoV-2 in high-risk patients, such as immuno-compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies ...Prevention of severe COVID-19 disease by SARS-CoV-2 in high-risk patients, such as immuno-compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies can be costly. Plant expression platforms allow substantial lower production costs compared to traditional bio-manufacturing platforms depending on mammalian cells in bioreactors. In this study, we describe the expression, production and purification of the originally human COVA2-15 antibody in plants. Our plant-produced mAbs demonstrated comparable neutralizing activity with COVA2-15 produced in mammalian cells. Furthermore, they exhibited similar capacity to prevent SARS-CoV-2 infection in a hamster model. To further enhance these biosimilars, we performed three glyco- and protein engineering techniques. First, to increase antibody half-life, we introduced YTE-mutation in the Fc tail; second, optimization of N-linked glycosylation by the addition of a C-terminal ER-retention motif (HDEL), and finally; production of mAb in plant production lines lacking β-1,2-xylosyltransferase and α-1,3-fucosyltransferase activities (FX-KO). These engineered biosimilars exhibited optimized glycosylation, enhanced phagocytosis and NK cell activation capacity compared to conventional plant-produced S15 and M15 biosimilars, in some cases outperforming mammalian cell produced COVA2-15. These engineered antibodies hold great potential for enhancing in vivo efficacy of mAb treatment against COVID-19 and provide a platform for the development of antibodies against other emerging viruses in a cost-effective manner.
External linksPlant Biotechnol J / PubMed:39563066 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.38 - 3.9 Å
Structure data

43794

9aru

EMDB-43794, PDB-9aru:
COVA2-15 fragment antigen binding in complex with SARS-CoV-2 6P-mut7 S protein
Method: EM (single particle) / Resolution: 3.9 Å

PDB-9b82:
Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody COVA2-15
Method: X-RAY DIFFRACTION / Resolution: 3.38 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 / neutralizing antibody / coronavirus / VIRAL PROTEIN/IMMUNE SYSTEM / Antibody / IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex

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