Correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals

  1. Kenji Maeda
  2. Masayuki Amano
  3. Yukari Uemura
  4. Kiyoto Tsuchiya
  5. Tomoko Matsushima
  6. Kenta Noda
  7. Yosuke Shimizu
  8. Asuka Fujiwara
  9. Yuki Takamatsu
  10. Yasuko Ichikawa
  11. Hidehiro Nishimura
  12. Mari Kinoshita
  13. Shota Matsumoto
  14. Hiroyuki Gatanaga
  15. Kazuhisa Yoshimura
  16. Shin-ichi Oka
  17. Ayako Mikami
  18. Wataru Sugiura
  19. Toshiyuki Sato
  20. Tomokazu Yoshida
  21. Shinya Shimada
  22. Hiroaki Mitsuya

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Abstract

While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT 50 ; assessed using infectious virions) with various determinants were examined and the potency of sera against variants of concerns was determined. Significant rise in NT 50 s was seen in sera on day 28 post-1st dose. A moderate inverse correlation was seen between NT 50 s and ages, but no correlation seen between NT 50 s and adverse effects. NT 50 s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd dose were greater in women than in men. The average half-life of NT 50 s was ~ 68 days, and 23.6% (49 out of 208 individuals) failed to show detectable neutralizing activity on day 150. While sera from elite-responders (NT 50 s > 1,500: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some sera with low NT 50 s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.

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  1. Version published to 10.1038/s41598-021-01930-y
  2. Version published to 10.21203/rs.3.rs-847396/v1 on Research Square
  3. ScreenIT

    SciScore for 10.1101/2021.07.27.21261237: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The Ethics Committees from the Kumamoto General Hospital and NCGM approved this study (Kumamoto General Hospital No. 180, and NCGM-G-004176-00, respectively).
    Consent: Each participant provided a written informed consent, and this study abided by the Declaration of Helsinki principles.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Measurement of anti-SARS-CoV-2 antibody titers: Measurement of 3 anti-SARS-CoV-2 antibody levels (anti-S1-IgG, anti-S1-IgM, and anti-N-IgG) in each participant was performed using the chemiluminescence enzyme immunoassay (CLEIA) platform (HISCL) manufactured by Sysmex Co. (Kobe, Japan) as previously reported24.
    anti-SARS-CoV-2
    suggested: None
    anti-S1-IgG, anti-S1-IgM,
    suggested: None
    anti-N-IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    VeroE6TMPRSS2 cells were maintained in DMEM supplemented with 10% FCS, 100 µg/ml of penicillin, 100 µg/ml of streptomycin, and 1 mg/mL of G418.
    VeroE6TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    The merTools package (version 0.5.2) in R software was used for prediction.
    merTools
    suggested: None

    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.

  4. Version published to 10.1101/2021.07.27.21261237v1 on medRxiv