The evaluation of factors affecting antibody response after administration of the BNT162b2 vaccine: a prospective study in Japan

  1. Toshiya Mitsunaga
  2. Yuhei Ohtaki
  3. Yutaka Seki
  4. Masakata Yoshioka
  5. Hiroshi Mori
  6. Midori Suzuka
  7. Syunsuke Mashiko
  8. Satoshi Takeda
  9. Kunihiro Mashiko

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Abstract

The aim of this study was to evaluate the antibody reaction after administration of the BNT162b2 vaccine, and to reveal the factors that affect antibody production. This prospective study was carried out in the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, in Tokyo, Japan, from April 15, 2021 to June 09, 2021. All our hospital’s workers who were administered the BNT162b2 vaccine as part of a routine program were included in this study. We calculated the anti-SARS-CoV-2 spike-specific antibody titter (1) before vaccination, (2) 7 to 20 days after the first vaccination, and (3) A total of 7 to 20 days after the second vaccination. The low-antibody titer group (LABG) was defined as the group having less than 25 percentiles of antibody titer. Univariate and Multivariate logistic regression analysis were performed to ascertain the effects of factors on the likelihood of LABG. A total of 374 participants were eventually included in our study, and they were divided into 94 LABG and 280 non-LABG. All samples showed significant antibody elevation in the second antibody test, with a mean value of 3,476 U/mL. When comparing the LABG and non-LABG groups, the median age, blood sugar, and HbA1c were significantly higher in the LABG group. The rates of participants with low BMI (<18.5) and high BMI (>30) were significantly higher in the LABG group. The proportion of chronic lung disease, hypertension, diabetes, dyslipidemia, autoimmune disease, and cancer were significantly higher in the LABG group. Although there was no significant difference confirmed with respect to the exercise hours per day, the proportion of participants that did not perform outdoor exercises was significantly higher in the LABG group. The time interval between the second vaccination and the second antibody test, and between the first and the second vaccination was significantly longer in the non-LABG group. In the multivariate logistic regression analysis, older than 60 years, the past history of hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Again, our single-center study demonstrates that older than 60 years, hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Evidence from multi-center studies is needed to develop further vaccination strategies.

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  1. Version published to 10.7717/peerj.12316
  2. ScreenIT

    SciScore for 10.1101/2021.06.20.21259177: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The protocol for this research project was approved by a suitably constituted Ethics Committee of the institution and conforms to the provision of the Declaration of Helsinki (Committee of Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, Approval No. 2020-Ack-19), and written consent was obtained from all the human subjects.
    Consent: The protocol for this research project was approved by a suitably constituted Ethics Committee of the institution and conforms to the provision of the Declaration of Helsinki (Committee of Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, Approval No. 2020-Ack-19), and written consent was obtained from all the human subjects.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisStatistical analysis: A sample size of 460 participants was determined based upon 70% power, 0.05 significance level, 0.3 effect size, three allocation ration, and 20% attrition.

    Table 2: Resources

    Antibodies
    SentencesResources
    Data sources and measurements: A 5-ml blood sample was drawn from the intermediate cubital vein, and we determined the anti-SARS-CoV-2 antibody titer (Elecsys® Anti-SARS-CoV-2 S RUO, Roche Diagnostics K.K.) a) before vaccination (baseline), b) seven to twenty days after the first vaccination (first antibody test), and c) seven to twenty days after the second vaccination (second antibody test).
    anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analyzed with the Statistical Package for the Social Sciences, version 26.0 (SPSS, Chicago, IL, USA).
    Statistical Package for the Social Sciences
    suggested: (SPSS, RRID:SCR_002865)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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 has several limitations. First, we only diagnosed new Covid-19 infections to participants through symptoms of fever and common cold. Therefore, we were unable to identify asymptomatic infections. However, our data showed that the number of antibody-positive cases at baseline, without any previous episode of Covid-19 infection was only one (0.3%), and thus had low statistical power. Second, we only calculated the antibody titer but not the CD4 lymphocyte activity. Consequently, we could not evaluate the effect of these factors to the entire immune system. Third, we only included relatively healthy medical workers, but did not include participants with severe complications, and this may have reduced the difference between the LABG and non-LABG groups. Further large-scale studies that include participants with several concurrent conditions are needed in the future.

    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 10.1101/2021.06.20.21259177 on medRxiv