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Summary: This study describes a novel, neutralizing monoclonal antibody (mAb), 11D7, discovered by mouse immunization and hybridoma generation, against the parental Wuhan‐Hu‐1 RBD of SARS‐CoV‐2. We further developed this mAb into a chimeric human IgG and recombinantly expressed it in plants to produce a mAb with human‐like, highly homogenous N‐linked glycans that has potential to impart greater potency and safety as a therapeutic. The epitope of 11D7 was mapped by competitive binding with well‐characterized mAbs, suggesting that it is a Class 4 RBD‐binding mAb that binds to the RBD outside the ACE2 binding site. Of note, 11D7 maintains recognition against the B.1.1.529 (Omicron) RBD, as well neutralizing activity. We also provide evidence that this novel mAb may be useful in providing additional synergy to established antibody cocktails, such as Evusheld™ containing the antibodies tixagevimab and cilgavimab, against the Omicron variant. Taken together, 11D7 is a unique mAb that neutralizes SARS‐CoV‐2 through a mechanism that is not typical among developed therapeutic mAbs and by being produced in ΔXFT Nicotiana benthamiana plants, highlights the potential of plants to be an economic and safety‐friendly alternative platform for generating mAbs to address the evolving SARS‐CoV‐2 crisis. [ABSTRACT FROM AUTHOR]

Recombinant proteins have a broad range of applications from basic research to pharmaceutical development. Of utmost importance in the production of recombinant proteins is the selection of the best recombinant protein production system, such that high-quality and functional recombinant proteins are produced. Plants can produce a large quantity of recombinant proteins rapidly and economically. Glycoengineering has created "humanized" plant lines that can produce glycoproteins with specific human glycans with a high level of homogeneity on demand. Here, a detailed protocol was provided to produce a large, multisubunit, and complex bispecific antibody that targets two distinct viruses. The successful production of this multiple-subunit protein demonstrated that plants are the optimal system for the production of recombinant proteins of various sizes and complexity, which can be employed for various applications including diagnostics, therapeutics, and vaccines to combat current and future pandemics., (Copyright © 2021 Elsevier Inc. All rights reserved.)