Persistently reduced humoral and sustained cellular immune response from first to third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients

  1. Hamza Mahmood Bajwa
  2. Frederik Novak
  3. Anna Christine Nilsson
  4. Christian Nielsen
  5. Dorte K. Holm
  6. Kamilla Østergaard
  7. Agnes Hauschultz Witt
  8. Keld-Erik Byg
  9. Isik S. Johansen
  10. Kristen Mittl
  11. William Rowles
  12. Scott S. Zamvil
  13. Riley Bove
  14. Joseph J. Sabatino
  15. Tobias Sejbaek

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Abstract

No abstract available

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  1. Version published to 10.1016/j.msard.2022.103729
  2. ScreenIT

    SciScore for 10.1101/2022.01.27.22269944: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Standard protocol approvals, registrations, patient consents, and monitoring: Both written and oral consent was taken from all participants prior to inclusion.
    IRB: The Danish study followed national laws adhering to good clinical practice and was approved by the Danish National Committee on Health Research Ethics (Protocol no. S-20200068C) and Danish Data Protection Agency (journal no. 20/19,878).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    This assay has shown excellent correlation with the first WHO (World Health Organization) International Standard for anti-SARS-CoV-2 immunoglobulin (NIBSC code 20/136) (20), enabling the issuing of immunogenicity results in standardized units; binding antibody units (BAU)/mL for a binding assay format as the SARS-CoV-2 IgG II Quant assay.
    anti-SARS-CoV-2 immunoglobulin
    suggested: None
    Folllowing stimulation, cells were washed and stained with the following antibody panel: CD4 Alexa 488 (OKT4)
    CD4
    suggested: None
    Software and Algorithms
    SentencesResources
    Human Peripheral Blood Mononuclear Cell Isolation: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood using density gradient centrifugation (Lymphoprep™) and cryopreserved using DMSO-containing freezing medium and stored at – 196 °C until flow cytometric analyses Antibody assay and flow cytometry: We measured IgG antibodies against the SARS-CoV-2 spike RBD in plasma samples as described by Novak et al. (4) using the SARS-CoV-2 IgG II Quant assay (Abbott Laboratories), which is a quantitative chemiluminescent microparticle immunoassay (19).
    Abbott Laboratories
    suggested: None
    The mathematical relationship of the Abbott AU/mL unit to the WHO BAU/mL unit follows the equation BAU/mL = 0.142xAU/mL, corresponding to a cut-off at 7.1 BAU/mL.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Samples were analyzed on a BD FACSCanto™ II flow cytometer with BD FACSDiva software.
    BD FACSDiva
    suggested: (BD FACSDiva Software, RRID:SCR_001456)

    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:
    There were limitations to our study. The short inclusion timeframe resulted in a few missing samples at V4 and V5. Furthermore, the cut-off levels presented in this study reflect reactivity against alpha variants of SARS-CoV-2, but not more recent variants of concern, including the delta or omicron variants. In summary, in contrast to prior studies, in this longitudinal cohort we found no significant increased protective benefit from a humoral or cellular perspective with administration of a third SARS-CoV-2 mRNA vaccination. These findings have important clinical implications and suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2022.01.27.22269944v1 on medRxiv