Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies

  1. Carlota Dobaño
  2. Rebeca Santano
  3. Alfons Jiménez
  4. Marta Vidal
  5. Jordi Chi
  6. Natalia Rodrigo Melero
  7. Matija Popovic
  8. Rubén López-Aladid
  9. Laia Fernández-Barat
  10. Marta Tortajada
  11. Francisco Carmona-Torre
  12. Gabriel Reina
  13. Antoni Torres
  14. Alfredo Mayor
  15. Carlo Carolis
  16. Alberto L. García-Basteiro
  17. Ruth Aguilar
  18. Gemma Moncunill
  19. Luis Izquierdo

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Abstract

No abstract available

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  1. Version published to 10.1016/j.trsl.2021.02.006
  2. ScreenIT

    SciScore for 10.1101/2020.12.19.20248551: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Study approval: The research was carried out according to the principles of the Declaration of Helsinki and informed consent was obtained.
    IRB: Samples analyzed in this study received ethical clearance for immunological evaluation and/or inclusion as controls in immunoassays, and the protocols and informed consent forms were approved by the Institutional Review Board at Hospital Clínic in Barcelona (Refs.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Measurement of IgM, IgG and IgA antibodies: qSAT assays to measure plasma IgG, IgA and IgM against SARS-CoV-2 N proteins were performed as reported (27) and analyzed in a Luminex 100/200 instrument.
    IgM, IgG
    suggested: None
    After sample incubation with beads, plates were washed and a labeled secondary antibody (anti-human IgG, IgM, or IgA) was added.
    anti-human IgG
    suggested: None
    IgA
    suggested: None
    To assess for crossreactivity, we performed correlations (Spearman) and heatmaps of antibody responses to SARS-CoV-2 and HCoV N antigens in prepandemic and pandemic samples separately, stratifying by rRT-PCR positivity and by high vs. low anti-N FL IgG responders, as appropriate.
    anti-N
    suggested: None

    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:
    Nevertheless, a limitation of this study is that the design and sample size did not allow unraveling the potential effect of baseline HCoV antibodies on the acquisition of COVID-19 immunity (63), which will be addressed in future longitudinal follow up analysis of our cohorts. This effect could be neutral, positive (boost of responses) or negative, whereby having antibodies to certain viruses could adversely determine the profile of responses upon SARS-CoV-2 infection (‘original antigenic sin’) (44, 45, 48) or interfere by antigen masking. Findings from a recent study argue against a protective role for crossreactive HCoV T cells in SARS-CoV-2 infection (37). In our study, we speculate that preexisting OC43 HCoV IgGs could be protective and, as a result, incoming SARS-CoV-2 infections would be more controlled and thus fewer antibodies induced against them. Unexpectedly, higher serological correlations were consistently obtained for SARS-CoV-2 and alpha-rather than beta-HCoVs despite having less homology at the primary aminoacid sequence level. The reactivity of the alpha- and beta-HCoVs clustered together within families, also by PCA analysis (data not shown). Therefore, it appears that crossreactivity is also and mostly driven by homologies at the conformational rather than the linear level. Overall, data indicated various degrees of moderate crossreactivity for SARS-CoV-2 and HCoV N antigens, but patterns were heterogeneous and not very strong, possibly as a result of a com...

    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 10.1101/2020.12.19.20248551 on medRxiv