Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors

  1. Rita E. Chen
  2. Matthew J. Gorman
  3. Daniel Y. Zhu
  4. Juan Manuel Carreño
  5. Dansu Yuan
  6. Laura A. VanBlargan
  7. Samantha Burdess
  8. Douglas A. Lauffenburger
  9. Wooseob Kim
  10. Jackson S. Turner
  11. Lindsay Droit
  12. Scott A. Handley
  13. Salim Chahin
  14. Parakkal Deepak
  15. Jane A. O’Halloran
  16. Michael A. Paley
  17. Rachel M. Presti
  18. Gregory F. Wu
  19. Florian Krammer
  20. Galit Alter
  21. Ali H. Ellebedy
  22. Alfred H.J. Kim
  23. Michael S. Diamond

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Abstract

No abstract available

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  1. Version published to 10.1016/j.medj.2021.11.004
  2. ScreenIT

    SciScore for 10.1101/2021.09.28.21264250: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: All individuals were enrolled at Washington University School of Medicine in studies that had received Institutional Review Board approval (202012081 (WU368) and 202012084 (COVaRiPAD)
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Plates were washed and sequentially incubated with an oligoclonal pool of SARS2-2, SARS2-11, SARS2-16, SARS2-31, SARS2-38, SARS2-57, and SARS2-71 (Liu et al., 2021d; VanBlargan et al.) anti-spike antibodies and HRP-conjugated goat anti-mouse IgG (Sigma, 12-349) in PBS supplemented with 0.1% saponin and 0.1% bovine serum albumin.
    SARS2-57
    suggested: None
    SARS2-71
    suggested: None
    anti-spike
    suggested: None
    anti-mouse IgG
    suggested: (Millipore Cat# 12-349, RRID:AB_390192)
    Unbound antibodies were washed away, and antigen-bound antibodies were detected by using a PE-coupled detection antibody for each subclass and isotype (IgG1, IgG3, IgA1, and IgM; Southern Biotech), and FcγR were fluorescently labeled with PE before addition to immune complexes (FcγR2a, FcγR3a; Duke Protein Production facility).
    antigen-bound
    suggested: None
    IgG1
    suggested: None
    IgG3
    suggested: None
    IgA1
    suggested: None
    PE median fluorescent intensity (MFI) is reported as a readout for antigen-specific antibody titers.
    antigen-specific
    suggested: None
    To measure antibody-dependent deposition of C3, lyophilized guinea pig complement (Cedarlane) was diluted in gelatin veronal buffer with calcium and magnesium (GBV++) (Boston BioProducts) and added to immune complexes.
    C3
    suggested: None
    Subsequently, C3 was detected with an anti-C3 fluorescein-conjugated goat IgG fraction detection antibody (Mpbio).
    anti-C3 fluorescein-conjugated goat IgG
    suggested: None
    Antibody-dependent cellular (ADCP) and neutrophil (ADNP) phagocytosis: Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent neutrophil phagocytosis (ADNP) were conducted according to the previously described protocols (Butler et al., 2019; Karsten et al., 2019).
    Antibody-dependent cellular ( ADCP
    suggested: None
    Antibody-dependent cellular phagocytosis ( ADCP )
    suggested: None
    antibody-dependent neutrophil phagocytosis ( ADNP
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Antibody-virus complexes were added to Vero-TMPRSS2 cell monolayers in 96-well plates and incubated at 37°C for 1 h.
    Vero-TMPRSS2
    suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)
    For ADCP, the immune complexes were incubated for 16–18 hours with THP-1 cells (1.25×105 THP-1 cells/mL) and for ADNP for 1 hour with RBC-lyzed whole blood.
    THP-1
    suggested: None
    Software and Algorithms
    SentencesResources
    All individuals were enrolled at Washington University School of Medicine in studies that had received Institutional Review Board approval (202012081 (WU368) and 202012084 (COVaRiPAD)
    COVaRiPAD
    suggested: None
    Analysis was performed using Prism 7 software (GraphPad), and values were reported as area under the curve (AUC).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Flow cytometry was performed with 5 Laser LSR Fortessa Flow Cytometer and analyzed using FlowJo V10.7.1
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    The data used to generate Fig 3e was graphed and analyzed using Python version 3.8.5 and the ‘plotly’ package (Sievert, 2020).
    Python
    suggested: (IPython, RRID:SCR_001658)
    All other data were graphed and analyzed in GraphPad Prism v8.4.3.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Limitations of study: We note several limitations in our study. (1) Due to the diversity of immunosuppressants used, the number in each treatment subgroup is relatively small, limiting the power of the statistical analysis; (2) The cohort we used was a subset of a larger CID cohort (Deepak et al., 2021) that included vaccinated patients receiving multiple immunosuppressive treatment modalities. Only those on monotherapy regimens were evaluated in our study to eliminate confounding by use of concomitant immunosuppressive agents; (3) We grouped subjects by treatment intervention but due to the small numbers did not account for underlying disease severity nor diagnosis, which independently could impact immune responses; (4) Our study focused on subjects immunized with the Pfizer BNT162b2 mRNA vaccine. Separate studies are needed with other vaccine platforms; (5) Our studies focused on the impact of immunosuppression on serum antibody responses after vaccination and did not account for T cell and anamnestic responses, which also may confer protection; and (6) The small sample size precluded assessment of comorbidities, age, and sex on humoral responses. From a cohort of 74 patients with chronic inflammatory diseases on different immunosuppressive therapy, we observed a clear trend towards lower antibody neutralizing and Fc effector function responses after two doses of Pfizer BNT162b2 mRNA vaccination in those receiving TNFi. As these responses are even lower against emerging VOC...

    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.
    • Thank you for including a protocol registration statement.

    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 10.1101/2021.09.28.21264250v1 on medRxiv