Assessing anti‐SARS‐CoV‐2 cellular immunity in 571 vaccines by using an IFN‐γ release assay

  1. Masatoshi Wakui
  2. Yoshifumi Uwamino
  3. Yoko Yatabe
  4. Terumichi Nakagawa
  5. Akiko Sakai
  6. Toshinobu Kurafuji
  7. Ayako Shibata
  8. Yukari Tomita
  9. Masayo Noguchi
  10. Akiko Tanabe
  11. Tomoko Arai
  12. Akemi Ohno
  13. Hiromitsu Yokota
  14. Shunsuke Uno
  15. Wakako Yamasawa
  16. Yasunori Sato
  17. Mari Ikeda
  18. Akihiko Yoshimura
  19. Naoki Hasegawa
  20. Hideyuki Saya
  21. Mitsuru Murata

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Abstract

Memory T cell responses have been analyzed only in small cohorts of COVID‐19 vaccines. Herein, we aimed to assess anti‐SARS‐CoV‐2 cellular immunity in a large cohort using QuantiFERON assays, which are IFN‐γ release assays (IGRAs) based on short‐term whole blood culture. The study included 571 individuals receiving the viral spike (S) protein‐expressing BNT162b2 mRNA vaccine. QuantiFERON assays revealed antigen‐specific IFN‐γ production in most individuals 8 weeks after the second dose. Simultaneous flow cytometric assays to detect T cells expressing activation‐induced markers (AIMs) performed for 28 randomly selected individuals provided data correlating with the QuantiFERON data. Simultaneous IFN‐γ enzyme‐linked immunospot and AIM assays for another subset of 31 individuals, based on short‐term peripheral blood mononuclear cell culture, also indicated a correlation between IFN‐γ production and AIM positivity. These observations indicated the acquisition of T cell memory responses and supported the usability of IGRAs to assess cellular immunity. The QuantiFERON results were weakly correlated with serum IgG titers against the receptor‐binding domain of the S protein and were associated with pre‐vaccination infection and adverse reactions after the second dose. The present study revealed cellular immunity after COVID‐19 vaccination, providing insights into the effects and adverse reactions of vaccination.

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  1. Version published to 10.1002/eji.202249794
  2. ScreenIT

    SciScore for 10.1101/2021.12.14.21267039: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: From February 16th to March 9th, 2021, staffs of Keio University School of Medicine and Keio University Hospital (Tokyo, Japan) were recruited and included in the study after obtaining written informed consent from all 673 participants who were willing to receive the vaccine before the start of mass vaccination.
    IRB: The study design was approved by the Ethics Committee of Keio University School of Medicine (20200330).
    Sex as a biological variablenot detected.
    RandomizationThe cultured whole blood samples from these 28 randomly selected vaccinees were transferred to other tubes to separate and collect both cells and supernatants via centrifugation.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Determination of antibody titer: Immediately after sample collection, serum IgG titers against SARS-CoV-2 spike (S) protein S1 subunit receptor-binding domain (RBD) were measured using Alinity SARS-CoV-2 IgG II Quant reagents (Abbott Laboratories, Illinois, USA) and Alinity i Analyzer i (Abbott Laboratories, Illinois, USA) according to the manufacturer’s instructions.
    S1 subunit receptor-binding domain ( RBD
    suggested: None
    The fluorochrome-conjugated antibodies used for immunostaining included CD3 (LEU-4) FITC, CD4 APC-H7, CD8 PerCP-Cy5.5, CD69 PE, CD134 PE-Cy7, and CD137 APC (BD Biosciences, CA, USA)
    CD3
    suggested: None
    CD69
    suggested: None
    CD134
    suggested: None
    CD137
    suggested: None
    Software and Algorithms
    SentencesResources
    Determination of antibody titer: Immediately after sample collection, serum IgG titers against SARS-CoV-2 spike (S) protein S1 subunit receptor-binding domain (RBD) were measured using Alinity SARS-CoV-2 IgG II Quant reagents (Abbott Laboratories, Illinois, USA) and Alinity i Analyzer i (Abbott Laboratories, Illinois, USA) according to the manufacturer’s instructions.
    Abbott Laboratories
    suggested: None
    Flow cytometry data were analyzed using the BD FACSuite software (Becton and Dickinson).
    BD FACSuite
    suggested: None
    All the statistical analyses were performed using JMP version 15 (SAS Institute, North Carolina, USA).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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 10.1101/2021.12.14.21267039v1 on medRxiv