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

• Published in: Plant biotechnology journal 2025-01, Vol.23 (1), p.4-16
• Main Authors: Taeye, Steven W., Faye, Loïc, Morel, Bertrand, Schriek, Angela I., Umotoy, Jeffrey C., Yuan, Meng, Kuzmina, Natalia A., Turner, Hannah L., Zhu, Xueyong, Grünwald‐Gruber, Clemens, Poniman, Meliawati, Burger, Judith A., Caniels, Tom G., Fitchette, Anne‐Catherine, Desgagnés, Réjean, Stordeur, Virginie, Mirande, Lucie, Beauverger, Guillaume, Bree, Godelieve, Ozorowski, Gabriel, Ward, Andrew B., Wilson, Ian A., Bukreyev, Alexander, Sanders, Rogier W., Vezina, Louis‐Philippe, Beaumont, Tim, Gils, Marit J., Gomord, Véronique
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; antibody; Biological products; Bioreactors; Cell activation; COVID-19; COVID-19 - immunology; Cricetinae; Disease; Effectiveness; effector function; Engineering; Glycosylation; Humans; Mammalian cells; Mammals; Monoclonal antibodies; Mutation; Natural killer cells; Nicotiana - genetics; Nicotiana - metabolism; Pandemics; Phagocytosis; Plant cells; Plant layout; Plant production; Plants, Genetically Modified; Platforms; Production costs; Production lines; Prophylaxis; Protein engineering; Protein Engineering - methods; Proteins; SARS-CoV-2 - immunology; SARS‐CoV‐2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; structure; Viral diseases
• ISSN: 1467-7644; 1467-7652; 1467-7652
• DOI: 10.1111/pbi.14458

Summary 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.