Glyco engineered pentameric SARS-CoV-2 IgMs show superior activities compared to IgG1 orthologues

Frontiers in Immunology

Immunology

Esther Föderl-Höbenreich¹  Kurt Zatloukal¹  Herta Steinkellner²  Roman Palt²  Lukas Eidenberger²  Richard Strasser²  Lin Sun²  Somanath Kallolimath²  Florian Pruckner²  Qiang Chen³ 

[1]Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria

[2]Institute of Plant Biotechnology and Cell Biology, Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria

[3]The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, United States

关键词: pentameric IgM;    plant expression;    glycosylation;    monoclonal antibodies;    SARS-CoV-2;   

DOI  :  10.3389/fimmu.2023.1147960

 received in 2023-01-19, accepted in 2023-05-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

Immunoglobulin M (IgM) is the largest antibody isotype with unique features like extensive glycosylation and oligomerization. Major hurdles in characterizing its properties are difficulties in the production of well-defined multimers. Here we report the expression of two SARS-CoV-2 neutralizing monoclonal antibodies in glycoengineered plants. Isotype switch from IgG1 to IgM resulted in the production of IgMs, composed of 21 human protein subunits correctly assembled into pentamers. All four recombinant monoclonal antibodies carried a highly reproducible human-type N-glycosylation profile, with a single dominant N-glycan species at each glycosite. Both pentameric IgMs exhibited increased antigen binding and virus neutralization potency, up to 390-fold, compared to the parental IgG1. Collectively, the results may impact on the future design of vaccines, diagnostics and antibody-based therapies and emphasize the versatile use of plants for the expression of highly complex human proteins with targeted posttranslational modifications.

【 授权许可】

Unknown   
Copyright © 2023 Kallolimath, Palt, Föderl-Höbenreich, Sun, Chen, Pruckner, Eidenberger, Strasser, Zatloukal and Steinkellner