Jugler Collin, Sun Haiyan, Chen Qiang
The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Vaccines (Basel). 2021 Nov 20;9(11):1365. doi: 10.3390/vaccines9111365.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has caused more than 4.5 million deaths worldwide. Severe and fatal cases of COVID-19 are often associated with increased proinflammatory cytokine levels including interleukin 6 (IL-6) and acute respiratory distress syndrome. In this study, we explored the feasibility of using plants to produce an anti-IL-6 receptor (IL-6R) monoclonal antibody (mAb) and examined its utility in reducing IL-6 signaling in an in vitro model, which simulates IL-6 induction during SARS-CoV-2 infection. The anti-IL6R mAb (IL6RmAb) was quickly expressed and correctly assembled in leaves. Plant-produced IL6RmAb (pIL6RmAb) could be enriched to homogeneity by a simple purification scheme. Furthermore, pIL6RmAb was shown to effectively inhibit IL-6 signaling in a cell-based model system. Notably, pIL6RmAb also suppressed IL-6 signaling that was induced by the exposure of human peripheral blood mononuclear cells to the spike protein of SARS-CoV-2. This is the first report of a plant-made anti-IL-6R mAb and its activity against SARS-CoV-2-related cytokine signaling. This study demonstrates the capacity of plants for producing functionally active mAbs that block cytokine signaling and implies their potential efficacy to curb cytokine storm in COVID-19 patients.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是当前新冠疫情的病原体，已在全球造成超过450万人死亡。新冠重症和致死病例通常与促炎细胞因子水平升高有关，包括白细胞介素6（IL-6）和急性呼吸窘迫综合征。在本研究中，我们探讨了利用植物生产抗IL-6受体（IL-6R）单克隆抗体（mAb）的可行性，并在体外模型中检测了其在减少IL-6信号传导方面的效用，该模型模拟了SARS-CoV-2感染期间的IL-6诱导过程。抗IL-6R单克隆抗体（IL6RmAb）在叶片中快速表达并正确组装。植物产生的IL6RmAb（pIL6RmAb）可通过简单的纯化方案富集至同质。此外，pIL6RmAb在基于细胞的模型系统中被证明能有效抑制IL-6信号传导。值得注意的是，pIL6RmAb还抑制了人外周血单核细胞暴露于SARS-CoV-2刺突蛋白所诱导的IL-6信号传导。这是关于植物制造的抗IL-6R单克隆抗体及其对SARS-CoV-2相关细胞因子信号传导活性的首次报道。本研究证明了植物生产具有功能活性、可阻断细胞因子信号传导的单克隆抗体的能力，并暗示了其在遏制新冠患者细胞因子风暴方面的潜在疗效。
