Anti-CD38 therapy impairs SARS-CoV-2 vaccine response against alpha and delta variants in patients with multiple myeloma

  1. Soledad Henriquez
  2. Jérémie Zerbit
  3. Timothée Bruel
  4. Amani Ouedrani
  5. Delphine Planas
  6. Paul Deschamps
  7. Isabelle Staropoli
  8. Jérôme Hadjadj
  9. Bruno Varet
  10. Natalia Ermak
  11. Didier Bouscary
  12. Lise Willems
  13. Guillemette Fouquet
  14. Justine Decroocq
  15. Patricia Franchi
  16. Benedicte Deau-Fischer
  17. Benjamin Terrier
  18. Jérôme Tamburini
  19. Lucienne Chatenoud
  20. Olivier Schwartz
  21. Marguerite Vignon

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Abstract

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  1. Version published to 10.1182/blood.2021013714
  2. ScreenIT

    SciScore for 10.1101/2021.08.08.21261769: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: A written informed consent was obtained from all the patients for clinical data recording and blood samples collection in agreement with the declaration of Helsinki.
    IRB: The study protocol was approved by the institutional review board of Cochin Hospital (CLEP N°: AAA-2021-08041).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationContamination: Cells were tested negative for mycoplasma.

    Table 2: Resources

    Antibodies
    SentencesResources
    S-Flow assay: Anti-spike IgG and IgA antibodies were quantified using the S-Flow assay as previously described (Grzelak et al., 2020).
    Anti-spike IgG
    suggested: None
    IgA
    suggested: None
    After 30min of incubation at 4°C, cells were washed with PBS, and stained using anti-Hu IgG FC-Alexafluor 647 antibody (109-605-170, Jackson ImmunoResearch) and anti-Hu IgA alphaChain-Alexafluor 488 antibodies (109-545-011, Jackson ImmunoResearch) for 30min at 4°C.
    anti-Hu IgG
    suggested: (BD Biosciences Cat# 557075, RRID:AB_396573)
    anti-Hu IgA
    suggested: None
    To standardize the results, a binding units (BU) was calculated using a serially diluted human anti-S monoclonal antibody as reference (Grzelak et al., 2021).
    anti-S
    suggested: None
    Briefly, day 0, sterile PVDF strips (Millipore, Saint-Quentin-en-Yvelines, France) were coated overnight at 4°C with an IFNγ antibody (U-CyTech, Utrecht, Netherlands).
    IFNγ
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, 293T cells stably expressing the S protein (293T Spike cells) and 293T Empty cells as control were incubated with sera (1:300 dilution) in PBS containing 0.5% BSA and 2 mM EDTA.
    293T
    suggested: None
    The variant strains were isolated from nasal swabs using Vero E6 cells and amplified by one or two passages.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Viruses were sequenced directly on nasal swabs and after one or two passages on Vero cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    Positive controls were phytohemagglutinin PHA-P (Sigma-Aldrich) at a final concentration of 1 mg/ml and the CEFX Ultra SuperStim Pool (JPT Peptide Technologies GmbH, BioNTech
    BioNTech
    suggested: None
    Statistical analyses were performed using Prism software 9.2.0 (GraphPad).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    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:
    Our study had several limitations. Our main readout of anti-SARS-CoV-2 vaccine response was the production of NAbs, for which the threshold needed to protect patients from SARS-CoV-2 is still unknown. We investigated T-cell response in only half of the patients, due to technical limitations. The follow-up to evaluate SARS-CoV-2 infection incidence and severity was limited in time. Follow-up studies of larger cohorts of MM having received SARS-CoV-2 vaccine are needed to clearly determine the impact of vaccination strategies in this severely immunocompromised population. To summarize our findings, vaccinated MM patients had a delayed seroconversion, a decreased NAbs production, and an impaired cellular response to SARS-CoV-2 compared to healthy control the future evaluation of alternative strategies such as booster protocols will help defining an adapted procedure for MM patients and other severely immunocompromised patients.

    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 10.1101/2021.08.08.21261769v1 on medRxiv