Monoclonal antibodies capable of binding SARS-CoV-2 spike protein receptor-binding motif specifically prevent GM-CSF induction
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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.
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SciScore for 10.1101/2020.09.04.280081: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The monoclonal antibodies against human tetranectin were generated in Balb/C and C57BL/6 mice at the GenScript (Piscataway, NJ, USA) as previously described 23. human tetranectinsuggested: NoneOpen Surface Plasmon Resonance (SPR): We used the Nicoya Lifesciences gold-nanoparticle-based Open Surface Plasmon Resonance (OpenSPR) technology to estimate the binding kinetics and affinity of ACE2 or monoclonal antibodies to SARS-CoV-2 RBD or RBM following the … SciScore for 10.1101/2020.09.04.280081: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The monoclonal antibodies against human tetranectin were generated in Balb/C and C57BL/6 mice at the GenScript (Piscataway, NJ, USA) as previously described 23. human tetranectinsuggested: NoneOpen Surface Plasmon Resonance (SPR): We used the Nicoya Lifesciences gold-nanoparticle-based Open Surface Plasmon Resonance (OpenSPR) technology to estimate the binding kinetics and affinity of ACE2 or monoclonal antibodies to SARS-CoV-2 RBD or RBM following the manufacturer’s instructions. ACE2suggested: NoneExperimental Models: Cell Lines Sentences Resources Material: Murine macrophage-like RAW 264.7 cells were obtained from American Type Culture Collection (ATCC, Rockville, MD). RAW 264.7suggested: CLS Cat# 400319/p462_RAW-2647, RRID:CVCL_0493)Experimental Models: Organisms/Strains Sentences Resources The monoclonal antibodies against human tetranectin were generated in Balb/C and C57BL/6 mice at the GenScript (Piscataway, NJ, USA) as previously described 23. C57BL/6suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04341116 Recruiting Study of TJ003234 (Anti-GM-CSF Monoclonal Antibody) in Subje… NCT04351243 Active, not recruiting A Study to Assess the Efficacy and Safety of Gimsilumab in S… NCT04351152 Active, not recruiting Phase 3 Study to Evaluate Efficacy and Safety of Lenzilumab … NCT04376684 Active, not recruiting Investigating Otilimab in Patients With Severe Pulmonary COV… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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