SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody

Collin Jugler; Haiyan Sun; Qiang Chen

doi:10.3390/vaccines9111365

SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody

Vaccines (Basel). 2021 Nov 20;9(11):1365. doi: 10.3390/vaccines9111365.

Authors

Collin Jugler^{1

2}, Haiyan Sun^{1

2}, Qiang Chen^{1

2}

Affiliations

¹ The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
² School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.

Abstract

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.

Keywords: COVID-19; IL-6 receptor (IL-6R); SARS-CoV-2; cytokine storm; interleukin 6 (IL-6); monoclonal antibody (mAb); plant-made antibody; plant-made therapeutics; sarilumab; spike protein (S).