Cellular and Humoral Immune Response to a Third Dose of BNT162b2 COVID-19 Vaccine – A Prospective Observational Study

  1. Jonas Herzberg
  2. Bastian Fischer
  3. Heiko Becher
  4. Ann-Kristin Becker
  5. Human Honarpisheh
  6. Salman Yousuf Guraya
  7. Tim Strate
  8. Cornelius Knabbe

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Abstract

Since the introduction of various vaccines against SARS-CoV-2 at the end of 2020, infection rates have continued to climb worldwide. This led to the establishment of a third dose vaccination in several countries, known as a booster. To date, there has been little real-world data about the immunological effect of this strategy.

Methods

We compared the humoral- and cellular immune response before and after the third dose of BioNTech/Pfizer vaccine BNT162b2, following different prime-boost regimen in a prospective observational study. Humoral immunity was assessed by determining anti-SARS-CoV-2 binding antibodies using a standardized quantitative assay. In addition, neutralizing antibodies were measured using a commercial surrogate ELISA-assay. Interferon-gamma release was measured after stimulating blood-cells with SARS-CoV-2 specific peptides using a commercial assay to evaluate the cellular immune response.

Results

We included 243 health-care workers who provided blood samples and questionnaires pre- and post- third vaccination. The median antibody level increased significantly after the third vaccination dose to 2663.1 BAU/ml vs. 101.4 BAU/ml (p < 0.001) before administration of the booster dose. This was also detected for neutralizing antibodies with a binding inhibition of 99.68% ± 0.36% vs. 69.06% ± 19.88% after the second dose (p < 0.001). 96.3% of the participants showed a detectable T-cell-response after the booster dose with a mean interferon-gamma level of 2207.07 mIU/ml ± 1905 mIU/ml.

Conclusion

This study detected a BMI-dependent antibody increase after the third dose of BNT162b2 following different vaccination protocols. All participants showed a significant increase in their immune response. This, in combination with the low rate of post-vaccination-symptoms underlines the potential beneficial effect of a BNT162b2-booster dose.

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  1. Version published to 10.3389/fimmu.2022.896151
  2. ScreenIT

    SciScore for 10.1101/2022.03.10.22272204: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written and informed consent before inclusion.
    IRB: This study was prospectively registered at the German Clinical Trial Register (DRKS00021270) after approval by the Ethics Committee of the Medical Association Schleswig-Holstein.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SARS-CoV-2-IgG antibodies: The anti-SARS-CoV-2-igG antibody-titer was expressed in Binding Antibody Units per ml (BAU/ml) to stay in accordance with the WHO standard.
    Anti-SARS-CoV-2-IgG
    suggested: None
    Antibodies were determined by using a fully automated quantitative anti-SARS-CoV-2-assay (IgG) from Abbott (Chicago, USA).
    anti-SARS-CoV-2-assay (IgG
    suggested: None
    Neutralizing antibodies against SARS-CoV-2: To evaluate the neutralizing anti-SARS-CoV-2 antibodies, all samples were additionally tested using the NeutraLISA™ SARS-CoV-2 Neutralization Antibody Detection KIT (Euroimmun, Lübeck, Germany).
    anti-SARS-CoV-2
    suggested: None
    To investigate the joint effect of age, sex, body mass index and current smoking on the relative increase of antibody-level, a linear regression analysis was done to take the antibody level before booster into account.
    antibody-level
    suggested: None
    Software and Algorithms
    SentencesResources
    Antibodies were determined by using a fully automated quantitative anti-SARS-CoV-2-assay (IgG) from Abbott (Chicago, USA).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical analysis was made using IBM SPSS Statistics Version 25 (IBM Co., Armonk, NY, USA).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    In addition, GraphPad Prism 9 and IBM SPSS Statistics Version 25 (IBM Co., Armonk, NY, USA) were used for graphics.
    GraphPad
    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: We detected the following sentences addressing limitations in the study:
    Limitation: Despite the fact this study benefits from its real-life data in an important group of health-care workers, and a relatively large number of participants, it comes with some limitations. This study is limited by its single-center design. The inclusion of health-care workers led to the overrepresentation of women and younger people, whereas groups with a higher risk for low immune response to vaccination, such as elderly and participants with an immunomodulatory treatment, are underrepresented. Unfortunately, the number of individuals in each group of vaccination protocols were unequally distributed, as there was no individual choice regarding the vaccine received.

    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 10.1101/2022.03.10.22272204 on medRxiv