Role of Immunoglobulin M and A Antibodies in the Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2

  1. Jéromine Klingler
  2. Svenja Weiss
  3. Vincenza Itri
  4. Xiaomei Liu
  5. Kasopefoluwa Y Oguntuyo
  6. Christian Stevens
  7. Satoshi Ikegame
  8. Chuan-Tien Hung
  9. Gospel Enyindah-Asonye
  10. Fatima Amanat
  11. Ian Baine
  12. Suzanne Arinsburg
  13. Juan C Bandres
  14. Erna Milunka Kojic
  15. Jonathan Stoever
  16. Denise Jurczyszak
  17. Maria Bermudez-Gonzalez
  18. Arthur Nádas
  19. Sean Liu
  20. Benhur Lee
  21. Susan Zolla-Pazner
  22. Catarina E Hioe

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people globally. Virus infection requires the receptor-binding domain (RBD) of the spike protein. Although studies have demonstrated anti-spike and -RBD antibodies to be protective in animal models, and convalescent plasma as a promising therapeutic option, little is known about immunoglobulin isotypes capable of blocking infection.

Methods

We studied spike- and RBD-specific immunoglobulin isotypes in convalescent and acute plasma/serum samples using a multiplex bead assay. We also determined virus neutralization activities in plasma and serum samples, and purified immunoglobulin fractions using a vesicular stomatitis pseudovirus assay.

Results

Spike- and RBD-specific immunoglobulin (Ig) M, IgG1, and IgA1 were produced by all or nearly all subjects at variable levels and detected early after infection. All samples displayed neutralizing activity. Regression analyses revealed that IgM and IgG1 contributed most to neutralization, consistent with IgM and IgG fractions’ neutralization potency. IgA also exhibited neutralizing activity, but with lower potency.

Conclusion

IgG, IgM, and IgA are critical components of convalescent plasma used for treatment of coronavirus disease 2019 (COVID-19).

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  1. ScreenIT

    SciScore for 10.1101/2020.08.18.20177303: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All study participants provided written consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The virus-sample mix was then added to Vero-CCL81 cells seeded 24 hours earlier and spinoculated.
    Vero-CCL81
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Two-tailed Mann-Whitney test, Spearman rank-order correlation test, and simple linear regressions were performed as designated in the figure legends using GraphPad Prism 8.
    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 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.

    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.

  2. Version published to 10.1093/infdis/jiaa784
  3. Version published to 10.1101/2020.08.18.20177303v3 on medRxiv
  4. Version published to 10.1101/2020.08.18.20177303v2 on medRxiv
  5. Version published to 10.1101/2020.08.18.20177303v1 on medRxiv