Plant‐produced <scp>SARS</scp>‐<scp>CoV</scp>‐2 antibody engineered towards enhanced potency and in vivo efficacy

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.

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Institutions

Publication Details

Journal
Plant Biotechnology Journal
Published
2024-11-19
DOI
https://doi.org/10.1111/pbi.14458
Citations
2
Primary Topic
Transgenic Plants and Applications
Type
article
Field-Weighted Citation Impact
0.77

Funders

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article

Plant‐produced SARS‐CoV‐2 antibody engineered towards enhanced potency and in vivo efficacy

Véronique Gomord, Meliawati Poniman, Ian A. Wilson, Alexander Bukreyev et al.
2 citations
Plant Biotechnology Journal
Transgenic Plants and Applications
0.77
article

Plant‐produced SARS‐CoV‐2 antibody engineered towards enhanced potency and in vivo efficacy

Véronique Gomord, Meliawati Poniman, Ian A. Wilson, Alexander Bukreyev, Steven W. de Taeye, Marit J. van Gils, Virginie Stordeur, Réjean Desgagnés, Natalia A. Kuzmina, Meng Yuan, Jeffrey C. Umotoy, Judith A. Burger, Anne‐Catherine Fitchette, Tim Beaumont, Gabriel Ozorowski, Lucie Mirande, Bertrand Morel, Hannah L. Turner, Clemens Grünwald‐Gruber, Loı̈c Faye, Angela I. Schriek, Xueyong Zhu, Andrew B. Ward, Tom G. Caniels, Guillaume Beauverger, Godelieve de Bree, Louis‐Philippe Vézina, Rogier W. Sanders
article en
2 citations

Abstract

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.

Plant Biotechnology JournalVol. 23(1)
Scripps Research Institute (US), Cornell University (US), Galveston College (US), Amsterdam University Medical Centers (NL), Weill Cornell Medicine (US), The University of Texas Medical Branch at Galveston (US), University of Amsterdam (NL), BOKU University (AT)
U.S. Department of Energy, Bill and Melinda Gates Foundation, amfAR, The Foundation for AIDS Research, Office of Science, Argonne National Laboratory
Openalex Percentile: Top 26%
Transgenic Plants and Applications
0.77
DOIOpen Access PDFOpenAlex
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