SARS-CoV-2 specific T cell and humoral immune responses upon vaccination with BNT162b2: a 9 months longitudinal study

  1. Junko S. Takeuchi
  2. Ami Fukunaga
  3. Shohei Yamamoto
  4. Akihito Tanaka
  5. Kouki Matsuda
  6. Moto Kimura
  7. Azusa Kamikawa
  8. Yumiko Kito
  9. Kenji Maeda
  10. Gohzoh Ueda
  11. Tetsuya Mizoue
  12. Mugen Ujiie
  13. Hiroaki Mitsuya
  14. Norio Ohmagari
  15. Wataru Sugiura

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Abstract

The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon the coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the long-term chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22–73 years who received the vaccine. We conducted seven surveys up to 8 months after the second vaccination dose. SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity. This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These immune responses are sustained for approximately 6 to 10 weeks but not for 7 months or later following the second vaccination, indicating the need for the booster dose (i.e., third vaccination).

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  1. Version published to 10.1038/s41598-022-19581-y
  2. Version published to 10.1101/2021.11.06.21265632v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.11.06.21265632: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol was approved by the Ethics Committee of NCGM, Japan (approval number: NCGM-A-004175-00).
    Consent: Written informed consent was obtained from all the participants before the baseline survey.
    Field Sample Permit: Briefly, 5 mL of whole blood specimens were collected in a collection tube containing sodium heparin (VP-H050K, Terumo, Japan) at four time points during the vaccination regimen.
    Sex as a biological variableBackground factors were treated as categorical variables in the models: age (<40 or ≥40 years), sex (men or women), and BMI (<25 or ≥25 kg/m2).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological Assays: We performed three serological assays to detect the IgM and IgG antibodies against SARS-CoV-2 spike protein (IgM-S and IgG-S, respectively) and IgG antibodies against SARS-CoV-2 nucleocapsid protein (IgG-N).
    SARS-CoV-2 spike protein (IgM-S
    suggested: None
    IgG-S, respectively) and IgG
    suggested: None
    SARS-CoV-2 nucleocapsid protein (IgG-N
    suggested: None
    The presence of IgG-N antibodies can indicate SARS-CoV-2 infection prior to the study and during follow-up, regardless of the vaccination status.
    IgG-N
    suggested: None
    Antibody-mediated inhibition of soluble human receptor protein (angiotensin-converting enzyme 2, hACE2) binding to the RBD of the viral S1 region was tested.
    Antibody-mediated inhibition of soluble human receptor protein ( angiotensin-converting enzyme 2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cells and Viruses: VeroE6TMPRSS2 cells [11] were obtained from the Japanese Collection of Research Bioresources (JCRB) Cell Bank (Osaka, Japan).
    VeroE6TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    To detect IgG-S, the AdviseDx SARS-CoV-2 IgG II assay was performed using the Abbott ARCHITECT® following the manufacturer’s protocol.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical analyses were conducted using STATA version 17.0.
    STATA
    suggested: (Stata, RRID:SCR_012763)

    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:
    However, this study has several limitations. First, our study was conducted in a small-scale cohort of hospital workers in a single medical institution in Japan; thus, our findings might not be generalized to other settings. Second, the sufficient level of neutralizing activity or cellular immunities that is enough to protect against SARS-CoV-2 infection is not well known. In this study, sufficient neutralizing activity levels were defined as IH ≥35% in ELISA-based semi-quantitative neutralization assay (NeutraLISA), and the positive results evaluated by NeutraLISA spanned a wide range of values when the samples were analyzed by an in vitro virological experiment (summarized in Supplementary Figure 2). Further studies are warranted to determine sufficient levels of SARS-CoV-2 IgG antibody, neutralizing antibody, and T cell responses against SARS-CoV-2 infection and the duration of immunity induced by the vaccine. In conclusion, our study demonstrated that BNT162b2 vaccination induces SARS-CoV-2 specific IgG-S antibody and T cell responses, which were detected on day 15 following the first dose and peaked after the second dose and gradually declined over time. Sufficient levels of these responses against SARS-CoV-2 infection were maintained for over six–ten weeks following the second dose of BNT162b2 vaccination, and these responses were detected earlier than the onset of neutralizing activity. Our study contributes to a better understanding of the humoral and cellular immune ...

    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

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  4. Version published to 10.1101/2021.11.06.21265632v1 on medRxiv