Monoclonal antibodies capable of binding SARS-CoV-2 spike protein receptor-binding motif specifically prevent GM-CSF induction.

Abstract

A severe acute respiratory syndrome (SARS)-like coronavirus 2 (SARS-CoV-2) has recently caused a pandemic COVID-19 disease that infected approximately 94 million and killed more than 2,000,000 people worldwide. Like the SARS-CoV, SARS-CoV-2 also employs a receptor-binding motif (RBM) of its envelope spike protein for binding the host angiotensin-converting enzyme 2 (ACE2) to gain viral entry. Currently, extensive efforts are being made to produce vaccines against a surface fragment of a SARS-CoV-2, such as the spike protein, in order to boost protective antibodies that can inhibit virus-ACE2 interaction to prevent viral entry. It was previously unknown how spike protein-targeting antibodies would affect innate inflammatory responses to SARS-CoV-2 infections. Here we generated a highly purified recombinant protein corresponding to the RBM of SARS-CoV-2, and used it to screen for cross-reactive monoclonal antibodies (mAbs). We found two RBM-binding mAbs that competitively inhibited its interaction with human ACE2, and specifically blocked the RBM-induced GM-CSF secretion in both human peripheral blood mononuclear cells and murine macrophage cultures. Our findings have suggested a possible strategy to prevent SARS-CoV-2-elicited "cytokine storm," and revealed a potentially anti-inflammatory and protective mechanism for SARS-CoV-2 spike-based vaccines.

• Authors: Xiaoling Qiang, Shu Zhu, Jianhua Li, Weiqiang Chen, Huan Yang, Ping Wang, Kevin J Tracey, Haichao Wang
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 111 Issue 1 Pg. 261-267 (01 2022) ISSN: 1938-3673 [Electronic] England
• PMID: 33759207 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2021 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals LLC on behalf of Society for Leukocyte Biology.

Chemical References

• Antibodies, Monoclonal
• Recombinant Proteins
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2
• Granulocyte-Macrophage Colony-Stimulating Factor
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2

Topics

• Amino Acid Motifs
• Angiotensin-Converting Enzyme 2 (metabolism)
• Animals
• Antibodies, Monoclonal (metabolism)
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Leukocytes, Mononuclear (metabolism)
• Macrophages (metabolism)
• Mice
• Protein Binding
• RAW 264.7 Cells
• Recombinant Proteins (metabolism)
• Spike Glycoprotein, Coronavirus (chemistry, metabolism)