Infection or a third dose of mRNA vaccine elicits neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients

  1. Xavier Charmetant
  2. Maxime Espi
  3. Ilies Benotmane
  4. Véronique Barateau
  5. Francoise Heibel
  6. Fanny Buron
  7. Gabriela Gautier-Vargas
  8. Marion Delafosse
  9. Peggy Perrin
  10. Alice Koenig
  11. Noëlle Cognard
  12. Charlène Levi
  13. Floriane Gallais
  14. Louis Manière
  15. Paola Rossolillo
  16. Eric Soulier
  17. Florian Pierre
  18. Anne Ovize
  19. Emmanuel Morelon
  20. Thierry Defrance
  21. Samira Fafi-Kremer
  22. Sophie Caillard
  23. Olivier Thaunat

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Abstract

Transplant recipients, who receive therapeutic immunosuppression to prevent graft rejection, are characterized by high coronavirus disease 2019 (COVID-19)–related mortality and defective response to vaccines. We observed that previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but not the standard two-dose regimen of vaccination, provided protection against symptomatic COVID-19 in kidney transplant recipients. We therefore compared the cellular and humoral immune responses of these two groups of patients. Neutralizing anti–receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies were identified as the primary correlate of protection for transplant recipients. Analysis of virus-specific B and T cell responses suggested that the generation of neutralizing anti-RBD IgG may have depended on cognate T-B cell interactions that took place in germinal center, potentially acting as a limiting checkpoint. High-dose mycophenolate mofetil, an immunosuppressive drug, was associated with fewer antigen-specific B and T follicular helper (T FH ) cells after vaccination; this was not observed in patients recently infected with SARS-CoV-2. Last, we observed that, in two independent prospective cohorts, administration of a third dose of SARS-CoV-2 mRNA vaccine restored neutralizing titers of anti-RBD IgG in about 40% of individuals who had not previously responded to two doses of vaccine. Together, these findings suggest that a third dose of SARS-CoV-2 mRNA vaccine improves the RBD-specific responses of transplant patients treated with immunosuppressive drugs.

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  1. Version published to 10.1126/scitranslmed.abl6141
  2. ScreenIT

    SciScore for 10.1101/2021.07.22.21260852: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol complied with the tenets of the Helsinki Declaration and was approved by the Institutional Review Board (approval number: 18/21 03, Comité de Protection des Personnes Ouest IV Nantes) and registered on clinicaltrial.gov as NCT04757883.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cells were then rinsed and incubated at room temperature with the relevant fluorescent antibodies for 30 minutes: CD3 (UHCT1), CD8 (SK1), CXCR3 (1C6), CXCR5 (RF8B2), CCR6 (11A9), CD25 (2A3), from BD Biosciences; CD4 (SK3), CD69 (FN50), CD137 (4B4-1), from Biolegend; and a Fixable Viability Dye (eBiosciences).
    CD3
    suggested: None
    UHCT1
    suggested: None
    CD8
    suggested: (BD Biosciences Cat# 346048, RRID:AB_400455)
    CXCR3
    suggested: None
    CXCR5
    suggested: None
    CCR6
    suggested: None
    CD25
    suggested: (BD Biosciences Cat# 558063, RRID:AB_2275535)
    CD69
    suggested: None
    CD137
    suggested: None
    Anti-nucleocapsid IgG antibodies: The Abbott anti-N IgG assay is an automated chemiluminescence microparticle immunoassay (CMIA) conducted and interpreted according to manufacturer guidelines.
    Anti-nucleocapsid IgG
    suggested: None
    anti-N IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Cells were then rinsed and incubated at room temperature with the relevant fluorescent antibodies for 30 minutes: CD3 (UHCT1), CD8 (SK1), CXCR3 (1C6), CXCR5 (RF8B2), CCR6 (11A9), CD25 (2A3), from BD Biosciences; CD4 (SK3), CD69 (FN50), CD137 (4B4-1), from Biolegend; and a Fixable Viability Dye (eBiosciences).
    BD Biosciences
    suggested: (BD Biosciences, RRID:SCR_013311)
    Biolegend
    suggested: (BioLegend, RRID:SCR_001134)
    Statistical analysis: All the analyses were carried out using GraphPad Prism v8.0 (San Diego, California USA).
    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: 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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04757883Not yet recruitingImmunological Follow-up After SARS CoV2 Vaccination in Kidne…

    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 10.1101/2021.07.22.21260852v1 on medRxiv