Institute of Plant Biotechnology and Cell Biology, Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria.
Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
Front Immunol. 2023 Jun 8;14:1147960. doi: 10.3389/fimmu.2023.1147960. eCollection 2023.
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.
免疫球蛋白 M（IgM）是最大的抗体同种型，具有广泛的糖基化和寡聚化等独特特征。表征其特性的主要障碍是难以生产具有明确定义的多聚体。在这里，我们报告了在糖基化工程植物中表达两种 SARS-CoV-2 中和单克隆抗体。从 IgG1 到 IgM 的同种型转换导致产生了由 21 个人蛋白亚基正确组装成五聚体的 IgM。所有四个重组单克隆抗体均带有高度可重现的人类 N-糖基化图谱，在每个糖基化位点上都有一种单一的主导 N-聚糖。与亲本 IgG1 相比，两种五聚体 IgM 均表现出增强的抗原结合和病毒中和效力，最高可达 390 倍。总的来说，这些结果可能会影响未来疫苗、诊断和基于抗体的治疗方法的设计，并强调植物在表达具有靶向翻译后修饰的高度复杂人类蛋白方面的多功能用途。
