IgA dominates the early neutralizing antibody response to SARS-CoV-2

  1. Delphine Sterlin
  2. Alexis Mathian
  3. Makoto Miyara
  4. Audrey Mohr
  5. François Anna
  6. Laetitia Claër
  7. Paul Quentric
  8. Jehane Fadlallah
  9. Hervé Devilliers
  10. Pascale Ghillani
  11. Cary Gunn
  12. Rick Hockett
  13. Sasi Mudumba
  14. Amélie Guihot
  15. Charles-Edouard Luyt
  16. Julien Mayaux
  17. Alexandra Beurton
  18. Salma Fourati
  19. Timothée Bruel
  20. Olivier Schwartz
  21. Jean-Marc Lacorte
  22. Hans Yssel
  23. Christophe Parizot
  24. Karim Dorgham
  25. Pierre Charneau
  26. Zahir Amoura
  27. Guy Gorochov

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Abstract

Early specific antibody responses against SARS-CoV-2 include IgG, IgM, and IgA, but IgA may neutralize virus and control infection to a larger extent.

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  1. Version published to 10.1126/scitranslmed.abd2223
  2. ScreenIT

    SciScore for 10.1101/2020.06.10.20126532: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All patients gave informed consent.
    IACUC: This study was approved by the local ethical committee of Sorbonne Université (n°2020-CER2020-21).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Ten additional patients with chest computed tomography (CT) scan displaying features suggesting a COVID-19 infection and tested positive for the presence of serum anti-SARS-CoV-2 antibodies were also included.
    anti-SARS-CoV-2
    suggested: None
    B-cell and T-cell phenotyping: Phenotyping was assessed on freshly isolated PBMCs stained with a combination of anti-human antibodies (Table S5).
    anti-human antibodies ( Table S5
    suggested: None
    SARS-CoV-2 specific IgA, IgM and IgG antibodies were measured in 214 serum samples from 135 patients with The Maverick (tm) SARS-CoV-2
    IgG
    suggested: (DB Biotech Cat# DB 135, RRID:AB_2315725)
    Figure S3 (related to Figure 2): Performance of photonic ring immunoassay to detect anti-S1-RBD and anti-NC antibodies Figure S4 (related to Figure 2): Early detection of anti-S1-RBD antibodies in serum from SARS-CoV-2 patients.
    anti-NC
    suggested: None
    anti-S1-RBD
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Pseudovirus production and permissive cell line generation: Pseudotyped vectors were produced by triple transfection of 293T cells as previously described (36).
    293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    To generate this cell line, HEK 293T cells were transduced at MOI 20 with an integrative lentiviral vector expressing human ACE2 gene under the control of UBC promoter.
    HEK 293T
    suggested: None
    Mix is then plated in Tissue Culture treated black 96-well plate (Costar) with 20 000 HEK 293T-hACE2 cells in suspension.
    HEK 293T-hACE2
    suggested: None
    Software and Algorithms
    SentencesResources
    Cells were acquired on a BD FACSCanto II Flow cytometer (BD biosciences) and analysed with FlowJo v10 software (FlowJo, LLC).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis was performed using GraphPad Prism software, V6 (GraphPad, San Diego).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    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: We detected the following sentences addressing limitations in the study:
    Our study presents several limitations. Functional mucosal immunity analysis was only carried out in BAL, and longitudinal studies are needed at various body sites in order to assess whether local SARS-CoV-2-specific IgA production might be more persistant than in blood. In addition, it remains to be confirmed whether the in vitro IgA neutralization efficacy of the purified IgA serum antibodies translates into a potent barrier effect, not only in recovered patients, but also in paucisymptomatic individuals and healthy carriers. In conclusion, we would like to stress the importance of mucosal immunity as an important defence mechanism against SARS-CoV-2 to be monitored in infected patients, as well as to recommend testing the usefulness of a vaccine protocol aimed at inducing a specific respiratory IgA response to SARS-CoV-2.

    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.

  3. Version published to 10.1101/2020.06.10.20126532 on medRxiv