Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding

This article has been Reviewed by the following groups

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Abstract

With the emergence and continued spread of the SARS-CoV-2 virus, and of the associated disease, coronavirus disease 2019 (COVID-19), there is an urgent need for improved understanding of how the body mounts an immune response to the virus. Here, we developed a competitive SARS-CoV-2 serological assay that can simultaneously determine whether an individual has developed antibodies against the SARS-CoV-2 Spike protein receptor-binding domain (RBD) and measure the proportion of these antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. Using this assay and 144 SARS-CoV-2 patient serum samples, we found that a majority of anti-RBD antibodies compete for ACE2 binding. These results not only highlight the need to design vaccines to generate such blocking antibodies but also demonstrate the utility of this assay to rapidly screen patient sera for potentially neutralizing antibodies.

Article activity feed

  1. SciScore for 10.1101/2020.05.27.20114652: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Patient Samples: All serum samples were obtained via antecubital venipuncture and collected into BD Vacutainer serum collection tubes in using protocols approved by the UCSF Institutional Review Board and in accordance with the Declaration of Helsinki.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Plates were again washed, and antibodies bound to the coated antigens detected using 20 μL of anti-human Fab (Jackson ImmunoResearch Laboratories 109-036-097, [1:5000]), anti-human IgM (Sigma-Aldrich A6907, [1:3000]), anti-human IgG (Sigma-Aldrich A0170, [1:3000]), or Protein L (Thermo Fisher Scientific 32420, [1:5000]) as indicated for 30 minutes at room temperature.
    anti-human Fab
    suggested: None
    anti-human IgM
    suggested: (Sigma-Aldrich Cat# A6907, RRID:AB_258318)
    anti-human IgG
    suggested: (Sigma-Aldrich Cat# A0170, RRID:AB_257868)
    Software and Algorithms
    SentencesResources
    All graphing and statistical analysis was performed in GraphPad Prism (Version 8.4.2).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results 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: No clinical trial numbers were referenced.


    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.