9B82

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody COVA2-15

Summary for 9B82

• Entry DOI: 10.2210/pdb9b82/pdb
• Descriptor: Spike protein S1, COVA2-15 antibody heavy chain, COVA2-15 antibody light chain, ... (4 entities in total)
• Functional Keywords: sars-cov-2, antibody, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 18
• Total formula weight: 431274.88

Authors

Yuan, M.,Zhu, X.,Wilson, I.A. (deposition date: 2024-03-28, release date: 2024-12-04, Last modification date: 2025-01-08)

Primary citation

de Taeye, S.W.,Faye, L.,Morel, B.,Schriek, A.I.,Umotoy, J.C.,Yuan, M.,Kuzmina, N.A.,Turner, H.L.,Zhu, X.,Grunwald-Gruber, C.,Poniman, M.,Burger, J.A.,Caniels, T.G.,Fitchette, A.C.,Desgagnes, R.,Stordeur, V.,Mirande, L.,Beauverger, G.,de Bree, G.,Ozorowski, G.,Ward, A.B.,Wilson, I.A.,Bukreyev, A.,Sanders, R.W.,Vezina, L.P.,Beaumont, T.,van Gils, M.J.,Gomord, V.
Plant-produced SARS-CoV-2 antibody engineered towards enhanced potency and in vivo efficacy.
Plant Biotechnol J, 23:4-16, 2025

PubMed 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.

PubMed: 39563066
DOI: 10.1111/pbi.14458

Experimental method

X-RAY DIFFRACTION (3.38 Å)