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 Nicotiana benthamiana 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.
【저자키워드】 COVID-19, SARS-CoV-2, Cytokine storm, sarilumab, interleukin 6 (IL-6), monoclonal antibody (mAb), IL-6 receptor (IL-6R), spike protein (S), plant-made therapeutics, plant-made antibody, 【초록키워드】 Efficacy, coronavirus, feasibility, IL-6, SARS-COV-2 infection, COVID-19 pandemic, monoclonal antibody, Peripheral blood, death, plant, utility, cytokine signaling, COVID-19 patients, mAb, acute respiratory distress, Nicotiana benthamiana, mononuclear cell, Proinflammatory cytokine, acute respiratory syndrome, syndrome, IL-6R, homogeneity, purification, IL-6 signaling, in vitro model, anti-IL-6R, shown, examined, caused, inhibit, reducing, the spike protein, expressed, suppressed, producing, anti-IL-6 receptor, 【제목키워드】 spike, interleukin 6,