Multiple sclerosis therapies differentially affect SARS-CoV-2 vaccine–induced antibody and T cell immunity and function

  1. Joseph J. Sabatino
  2. Kristen Mittl
  3. William M. Rowles
  4. Kira McPolin
  5. Jayant V. Rajan
  6. Matthew T. Laurie
  7. Colin R. Zamecnik
  8. Ravi Dandekar
  9. Bonny D. Alvarenga
  10. Rita P. Loudermilk
  11. Chloe Gerungan
  12. Collin M. Spencer
  13. Sharon A. Sagan
  14. Danillo G. Augusto
  15. Jessa R. Alexander
  16. Joseph L. DeRisi
  17. Jill A. Hollenbach
  18. Michael R. Wilson
  19. Scott S. Zamvil
  20. Riley Bove

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Abstract

Vaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects of MS DMTs on SARS-CoV-2 vaccine–specific immunity is needed, including quantitative and functional B and T cell responses.

METHODS

Spike-specific Ab and T cell responses were measured before and following SARS-CoV-2 vaccination in a cohort of 80 study participants, including healthy controls and patients with MS in 6 DMT groups: untreated and treated with glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NTZ), sphingosine-1-phosphate (S1P) receptor modulators, and anti-CD20 mAbs. Anti–spike-Ab responses were assessed by Luminex assay, VirScan, and pseudovirus neutralization. Spike-specific CD4 + and CD8 + T cell responses were characterized by activation-induced marker and cytokine expression and tetramer.

RESULTS

Anti-spike IgG levels were similar between healthy control participants and patients with untreated MS and those receiving GA, DMF, or NTZ but were reduced in anti-CD20 mAb– and S1P-treated patients. Anti-spike seropositivity in anti-CD20 mAb–treated patients was correlated with CD19 + B cell levels and inversely correlated with cumulative treatment duration. Spike epitope reactivity and pseudovirus neutralization were reduced in anti-CD20 mAb– and S1P-treated patients. Spike-specific CD4 + and CD8 + T cell reactivity remained robust across all groups, except in S1P-treated patients, in whom postvaccine CD4 + T cell responses were attenuated.

CONCLUSION

These findings from a large cohort of patients with MS exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines.

FUNDING

NIH grants 1K08NS107619, K08NS096117, R01AI159260, R01NS092835, R01AI131624, and R21NS108159; NMSS grants TA-1903-33713 and RG1701-26628; Westridge Foundation; Chan Zuckerberg Biohub; Maisin Foundation.

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  1. Version published to 10.1172/jci.insight.156978
  2. ScreenIT

    SciScore for 10.1101/2021.09.10.21262933: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All enrolled participants provided written, informed consent for this study, which was approved by the UCSF Committee on Human Research (IRB# 21-33240).
    IRB: All enrolled participants provided written, informed consent for this study, which was approved by the UCSF Committee on Human Research (IRB# 21-33240).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Samples were incubated for 1 hour at room temperature, washed, and stained with 1:2000 anti-human IgG Fc antibody PE (BioLegend #637310) in PBST for 30 minutes at room temperature.
    anti-human IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Flow cytometry analysis was completed using FlowJo (BD).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Enriched libraries were analyzed in BioAnalyzer (Agilent) and quantified by digital-droplet PCR.
    BioAnalyzer
    suggested: (BioAnalyzer 2100, RRID:SCR_019715)

    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.

    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 10.1101/2021.09.10.21262933 on medRxiv