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

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)...

Full description

Bibliographic Details
Main Authors: Collin Jugler, Haiyan Sun, Qiang Chen
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/11/1365
_version_ 1797508254994006016
author Collin Jugler
Haiyan Sun
Qiang Chen
author_facet Collin Jugler
Haiyan Sun
Qiang Chen
author_sort Collin Jugler
collection DOAJ
description 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 <i>Nicotiana benthamiana</i> 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.
first_indexed 2024-03-10T04:59:48Z
format Article
id doaj.art-0b310806add44e0da40974ac5a69bd0b
institution Directory Open Access Journal
issn 2076-393X
language English
last_indexed 2024-03-10T04:59:48Z
publishDate 2021-11-01
publisher MDPI AG
record_format Article
series Vaccines
spelling doaj.art-0b310806add44e0da40974ac5a69bd0b2023-11-23T01:53:51ZengMDPI AGVaccines2076-393X2021-11-01911136510.3390/vaccines9111365SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal AntibodyCollin Jugler0Haiyan Sun1Qiang Chen2The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USAThe Biodesign Institute, Arizona State University, Tempe, AZ 85287, USAThe Biodesign Institute, Arizona State University, Tempe, AZ 85287, USASevere 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 <i>Nicotiana benthamiana</i> 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.https://www.mdpi.com/2076-393X/9/11/1365SARS-CoV-2monoclonal antibody (mAb)COVID-19interleukin 6 (IL-6)IL-6 receptor (IL-6R)cytokine storm
spellingShingle Collin Jugler
Haiyan Sun
Qiang Chen
SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody
Vaccines
SARS-CoV-2
monoclonal antibody (mAb)
COVID-19
interleukin 6 (IL-6)
IL-6 receptor (IL-6R)
cytokine storm
title SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody
title_full SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody
title_fullStr SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody
title_full_unstemmed SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody
title_short SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody
title_sort sars cov 2 spike protein induced interleukin 6 signaling is blocked by a plant produced anti interleukin 6 receptor monoclonal antibody
topic SARS-CoV-2
monoclonal antibody (mAb)
COVID-19
interleukin 6 (IL-6)
IL-6 receptor (IL-6R)
cytokine storm
url https://www.mdpi.com/2076-393X/9/11/1365
work_keys_str_mv AT collinjugler sarscov2spikeproteininducedinterleukin6signalingisblockedbyaplantproducedantiinterleukin6receptormonoclonalantibody
AT haiyansun sarscov2spikeproteininducedinterleukin6signalingisblockedbyaplantproducedantiinterleukin6receptormonoclonalantibody
AT qiangchen sarscov2spikeproteininducedinterleukin6signalingisblockedbyaplantproducedantiinterleukin6receptormonoclonalantibody