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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number1365
JournalVaccines
Volume9
Issue number11
DOIs
StatePublished - Nov 2021
Externally publishedYes

Keywords

  • COVID-19
  • Cytokine storm
  • IL-6 receptor (IL-6R)
  • Interleukin 6 (IL-6)
  • Monoclonal antibody (mAb)
  • Plant-made antibody
  • Plant-made therapeutics
  • SARS-CoV-2
  • Sarilumab
  • Spike protein (S)

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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