Persistence of Immune Response in Health Care Workers After Two Doses BNT162b2 in a Longitudinal Observational Study

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

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Abstract

The mRNA-based vaccine BNT162b2 of BioNTech/Pfizer has shown high efficacy against SARS-CoV-2 infection and a severe course of the COVID-19 disease. However, little is known about the long-term durability of the induced immune response resulting from the vaccination.

Methods

In a longitudinal observational study in employees at a German hospital we compared the humoral and cellular immune response in 184 participants after two doses of the BioNTech/Pfizer vaccine (BNT162b2) with a mid-term follow-up after 9 months. Anti-SARS-CoV-2 binding antibodies were determined using both a quantitative and a semi-quantitative assay. For a qualitative assessment of the humoral immune response, we additionally measured neutralizing antibodies. Cellular immune response was evaluated by measuring Interferon-gamma release after stimulating blood-cells with SARS-CoV-2 specific peptides using a commercial assay.

Results

In the first analysis, a 100% humoral response rate was described after two doses of BNT162b2 vaccine with a mean antibody ratio of 8.01 ± 1.00. 9 months after the second dose of BNT162b2, serological testing showed a significant decreased mean antibody ratio of 3.84 ± 1.69 (p < 0.001). Neutralizing antibodies were still detectable in 96% of all participants, showing an average binding inhibition value of 68.20% ± 18.87%. Older age (p < 0.001) and obesity (p = 0.01) had a negative effect on the antibody persistence. SARS-CoV-2 specific cellular immune response was proven in 75% of individuals (mean Interferon-gamma release: 579.68 mlU/ml ± 705.56 mlU/ml).

Conclusion

Our data shows a declining immune response 9 months after the second dose of BNT162b2, supporting the potentially beneficial effect of booster vaccinations, the negative effect of obesity and age stresses the need of booster doses especially in these groups.

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  1. Version published to 10.3389/fimmu.2022.839922
  2. ScreenIT

    SciScore for 10.1101/2021.12.17.21267926: (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 prior to enrolment.
    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 fully automated semiquantitative anti-SARS-CoV-2-ELISA (IgG) from Euroimmun (Lübeck, Germany) was used to detect the S1 domain of the SARS-CoV-2 spike-protein.
    Anti-SARS-CoV-2-IgG
    suggested: None
    anti-SARS-CoV-2-ELISA (IgG
    suggested: None
    Neutralizing antibodies against SARS-CoV-2: All samples were analyzed for neutralizing anti-SARS-CoV-2 antibodies using the NeutraLISA™ SARS-CoV-2 Neutralization Antibody Detection KIT (Euroimmun, Lübeck, Germany) in accordance to the manufacturer’s instructions.
    anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    In addition, a fully automated quantitative anti-SARS-CoV-2-assay (IgG) from Abbott (Chicago, USA) was performed.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    In brief, 500 μl of heparinized blood was stimulated with SARS-CoV-2 specific peptides covering regions of the viral S1-domain.
    SARS-CoV-2
    suggested: (BioLegend Cat# 946101, RRID:AB_2892515)
    Graphics were elaborated using IBM SPSS Statistics Version 25 (IBM Co., Armonk, NY, USA) and GraphPad Prism 9.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    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: The major limitation of this trial is its single-center design. Due to the inclusion of hospital employees, women are relatively overrepresented and other groups with a higher risk are underrepresented. Especially elderly participants, with an age over 70 years, are not included in this study. It cannot be excluded that there were asymptomatic, undetected SARS-CoV-2 infections among the participants during the 9 months after second vaccination, which may lead to a slight bias in the results. Due to the use of different methods, it was not possible to compare the absolute values of antibody concentrations, T-cell responses or neutralizing antibodies over the follow-up-period. Further evaluations of antibody response after vaccination are needed, to investigate the longitudinal persistence of antibodies and the possible need for further booster vaccinations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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 10.1101/2021.12.17.21267926v1 on medRxiv