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Plant expression platforms allow substantial lower production costs compared to traditional bio\u2010manufacturing platforms depending on mammalian cells in bioreactors. In this study, we describe the expression, production and purification of the originally human COVA2\u201015 antibody in plants. Our plant\u2010produced mAbs demonstrated comparable neutralizing activity with COVA2\u201015 produced in mammalian cells. Furthermore, they exhibited similar capacity to prevent SARS\u2010CoV\u20102 infection in a hamster model. To further enhance these biosimilars, we performed three glyco\u2010 and protein engineering techniques. First, to increase antibody half\u2010life, we introduced YTE\u2010mutation in the Fc tail; second, optimization of <jats:italic>N<\/jats:italic>\u2010linked glycosylation by the addition of a C\u2010terminal ER\u2010retention motif (HDEL), and finally; production of mAb in plant production lines lacking \u03b2\u20101,2\u2010xylosyltransferase and \u03b1\u20101,3\u2010fucosyltransferase activities (FX\u2010KO). These engineered biosimilars exhibited optimized glycosylation, enhanced phagocytosis and NK cell activation capacity compared to conventional plant\u2010produced S15 and M15 biosimilars, in some cases outperforming mammalian cell produced COVA2\u201015. These engineered antibodies hold great potential for enhancing <jats:italic>in vivo<\/jats:italic> efficacy of mAb treatment against COVID\u201019 and provide a platform for the development of antibodies against other emerging viruses in a cost\u2010effective manner.<\/jats:p>","DOI":"10.1111\/pbi.14458","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T06:39:32Z","timestamp":1732084772000},"page":"4-16","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Plant\u2010produced <scp>SARS<\/scp>\u2010<scp>CoV<\/scp>\u20102 antibody engineered towards enhanced potency and in vivo efficacy"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-9230","authenticated-orcid":false,"given":"Steven W.","family":"de Taeye","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental 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