AUTHOR=Kallolimath Somanath , Palt Roman , Föderl-Höbenreich Esther , Sun Lin , Chen Qiang , Pruckner Florian , Eidenberger Lukas , Strasser Richard , Zatloukal Kurt , Steinkellner Herta TITLE=Glyco engineered pentameric SARS-CoV-2 IgMs show superior activities compared to IgG1 orthologues JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1147960 DOI=10.3389/fimmu.2023.1147960 ISSN=1664-3224 ABSTRACT=

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.