Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases

  1. Roya M. Dayam
  2. Jaclyn C. Law
  3. Rogier L. Goetgebuer
  4. Gary Y.C. Chao
  5. Kento T. Abe
  6. Mitchell Sutton
  7. Naomi Finkelstein
  8. Joanne M. Stempak
  9. Daniel Pereira
  10. David Croitoru
  11. Lily Acheampong
  12. Saima Rizwan
  13. Klaudia Rymaszewski
  14. Raquel Milgrom
  15. Darshini Ganatra
  16. Nathalia V. Batista
  17. Melanie Girard
  18. Irene Lau
  19. Ryan Law
  20. Michelle W. Cheung
  21. Bhavisha Rathod
  22. Julia Kitaygorodsky
  23. Reuben Samson
  24. Queenie Hu
  25. W. Rod Hardy
  26. Nigil Haroon
  27. Robert D. Inman
  28. Vincent Piguet
  29. Vinod Chandran
  30. Mark S. Silverberg
  31. Anne-Claude Gingras
  32. Tania H. Watts

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

No abstract available

Article activity feed

  1. Version published to 10.1172/jci.insight.159721
  2. Version published to 10.1101/2022.01.26.22269856v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.01.26.22269856: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the ethics boards of the University of Toronto (REB protocol #27673), Mount Sinai Hospital/Sinai Health System (
    Consent: Written informed consent was obtained from all participants prior to participation.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingResearchers were blinded to the identity and clinical details of the subjects.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Spike-pseudotyped lentivirus neutralization assays: The lentivirus neutralization assay and the generation of spike pseudotyped lentivirus particles were performed as described previously.25 Briefly, the lentivirus particles were generated by co-transfection in HEK293TN cells (System Biosciences, Palo Alto, CA, USA, LV900A-1) of the Wuhan Hu-1 sequence with a D614G mutation (wild-type SARS-CoV-2), or the variants B.1.617.2 (Delta), B.1.351 (Beta), and P.1 (Gamma) constructs with packaging (psPAX2, Addgene, Watertown, MA, USA, #12260) and reporter (luciferase expressing pHAGE-CMV-Luc2-IRES-ZsGreen-W, provided by Drs.
    HEK293TN
    suggested: RRID:CVCL_UL49)
    Recombinant DNA
    SentencesResources
    Spike-pseudotyped lentivirus neutralization assays: The lentivirus neutralization assay and the generation of spike pseudotyped lentivirus particles were performed as described previously.25 Briefly, the lentivirus particles were generated by co-transfection in HEK293TN cells (System Biosciences, Palo Alto, CA, USA, LV900A-1) of the Wuhan Hu-1 sequence with a D614G mutation (wild-type SARS-CoV-2), or the variants B.1.617.2 (Delta), B.1.351 (Beta), and P.1 (Gamma) constructs with packaging (psPAX2, Addgene, Watertown, MA, USA, #12260) and reporter (luciferase expressing pHAGE-CMV-Luc2-IRES-ZsGreen-W, provided by Drs.
    psPAX2
    suggested: RRID:Addgene_12260)
    pHAGE-CMV-Luc2-IRES-ZsGreen-W
    suggested: RRID:Addgene_164432)
    Software and Algorithms
    SentencesResources
    GraphPad Prism 9 was used to calculate 50% neutralization titer (ID50) using non-linear regression.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Samples were acquired on the BD LSR Fortessa flow cytometer using BD FACSDiva software.
    BD FACSDiva
    suggested: (BD FACSDiva Software, RRID:SCR_001456)
    Statistical analysis: T cell cytokine secretion data were analyzed using the LEGENDplex(tm) Data Analysis Software Suite and pandas data analysis library for Python and GraphPad Prism v9.3.1al.
    Python
    suggested: (IPython, RRID:SCR_001658)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    27 Antibody data were analyzed with R (version 4.1.1) using package ggplot2 and custom R scripts.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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:
    Some limitations of our study are the small numbers of study subjects in some of the groups and grouping together of drugs by class. T cell responses, including IL-4, IL-2 and IFN-γ production, showed a significant correlation with RBD and spike - specific antibody responses. There was substantial induction of T cell cytokines and release of cytotoxic molecules following spike peptide pool stimulation of PBMCs collected following one dose of vaccine. Some subgroups and parameters showed increases in T cell cytokines with two doses. Multivariate analysis of the data showed that several groups had decreased IFN-γ after dose 1 of vaccine, but these deficits were largely corrected following the second vaccine dose. When data were pooled for all subjects, it was apparent that the IL-4 response was particularly dependent on 2 doses of vaccine and showed a waning trend 3 months later. As IL-4 is an important mediator of B cell proliferation, which in turn impacts antibody levels and B cell memory,28 the lower IL-4 response after 1 dose as compared to 2 doses of vaccine highlights the need for second doses to maximize B cell responses. Taken together, our study shows generally robust T cell responses in most patient groups treated with immunosuppressants or biologics after 1 or 2 doses of mRNA vaccine, improving somewhat with a second dose but with some attenuation by 3 months after the second dose. We observed some deficits in antibody responses even after two doses of vaccine, part...

    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.

  4. Version published to 10.1101/2022.01.26.22269856v1 on medRxiv