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)...

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Autores principales:	Collin Jugler, Haiyan Sun, Qiang Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	SARS-CoV-2 monoclonal antibody (mAb) COVID-19 interleukin 6 (IL-6) IL-6 receptor (IL-6R) cytokine storm Medicine R
Acceso en línea:	https://doaj.org/article/0b310806add44e0da40974ac5a69bd0b
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spelling	oai:doaj.org-article:0b310806add44e0da40974ac5a69bd0b2021-11-25T19:11:40ZSARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody10.3390/vaccines91113652076-393Xhttps://doaj.org/article/0b310806add44e0da40974ac5a69bd0b2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1365https://doaj.org/toc/2076-393XSevere 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.Collin JuglerHaiyan SunQiang ChenMDPI AGarticleSARS-CoV-2monoclonal antibody (mAb)COVID-19interleukin 6 (IL-6)IL-6 receptor (IL-6R)cytokine stormMedicineRENVaccines, Vol 9, Iss 1365, p 1365 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 monoclonal antibody (mAb) COVID-19 interleukin 6 (IL-6) IL-6 receptor (IL-6R) cytokine storm Medicine R
spellingShingle	SARS-CoV-2 monoclonal antibody (mAb) COVID-19 interleukin 6 (IL-6) IL-6 receptor (IL-6R) cytokine storm Medicine R 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
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.
format	article
author	Collin Jugler Haiyan Sun Qiang Chen
author_facet	Collin Jugler Haiyan Sun Qiang Chen
author_sort	Collin Jugler
title	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_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_sort	sars-cov-2 spike protein-induced interleukin 6 signaling is blocked by a plant-produced anti-interleukin 6 receptor monoclonal antibody
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0b310806add44e0da40974ac5a69bd0b
work_keys_str_mv	AT collinjugler sarscov2spikeproteininducedinterleukin6signalingisblockedbyaplantproducedantiinterleukin6receptormonoclonalantibody AT haiyansun sarscov2spikeproteininducedinterleukin6signalingisblockedbyaplantproducedantiinterleukin6receptormonoclonalantibody AT qiangchen sarscov2spikeproteininducedinterleukin6signalingisblockedbyaplantproducedantiinterleukin6receptormonoclonalantibody
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SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody

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