Immunological imprinting of the antibody response in COVID-19 patients

  1. Teresa Aydillo
  2. Alexander Rombauts
  3. Daniel Stadlbauer
  4. Sadaf Aslam
  5. Gabriela Abelenda-Alonso
  6. Alba Escalera
  7. Fatima Amanat
  8. Kaijun Jiang
  9. Florian Krammer
  10. Jordi Carratala
  11. Adolfo García-Sastre

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Abstract

In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

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  1. Version published to 10.1038/s41467-021-23977-1
  2. ScreenIT

    SciScore for 10.1101/2020.10.14.20212662: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Then, the cells were incubated with mAB 1C7 (anti-SARS nucleoprotein antibody, kindly provided by Dr. Moran) at a dilution of 1:1000 in 1% milk in PBST and incubated for 1hr at room temperature.
    anti-SARS
    suggested: None
    The plates were washed three times with PBS-T and 50 ul anti-human IgG (Fab-specific) horseradish peroxidase antibody (HRP, Sigma, #A0293) diluted 1:3,000 in PBS-T containing 1% milk powder was added to all wells and incubated for 1 h at room temperature.
    anti-human IgG
    suggested: (Sigma-Aldrich Cat# A0293, RRID:AB_257875)
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, Vero E6 cells were seeded in a 96-well cell culture plate with complete Dulbecco’s Modified Eagle Medium (cDMEM)(Corning) [(Penicillin-streptomycin (Corning), non-essential amino acids (Corning), 10% fetal bovine serum (FBS) (Peak)].
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    The results were recorded in Microsoft Excel and the endpoint titer and area under the curve values calculated in GraphPad Prism.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Chicken red blood cells (RBCs) (Lampire Biological) at 0.5% in HA buffer (50 μL) were added and incubated 45 minutes at 4°C.
    Lampire Biological
    suggested: None
    Correlation (Pearson), linear regression, local regression fit-line and related-sample comparison (Friedman’s two-way analysis of variance by ranks and pairwise comparison adjusted by Bonferroni correction) were performed using IBM SPSS Statistics (version 26).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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.

  3. Version published to 10.1101/2020.10.14.20212662v1 on medRxiv