Age-dependent Immune Response to the Biontech/Pfizer BNT162b2 Coronavirus Disease 2019 Vaccination

  1. Lisa Müller
  2. Marcel Andrée
  3. Wiebke Moskorz
  4. Ingo Drexler
  5. Lara Walotka
  6. Ramona Grothmann
  7. Johannes Ptok
  8. Jonas Hillebrandt
  9. Anastasia Ritchie
  10. Denise Rabl
  11. Philipp Niklas Ostermann
  12. Rebekka Robitzsch
  13. Sandra Hauka
  14. Andreas Walker
  15. Christopher Menne
  16. Ralf Grutza
  17. Jörg Timm
  18. Ortwin Adams
  19. Heiner Schaal

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Abstract

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to the development of various vaccines. Real-life data on immune responses elicited in the most vulnerable group of vaccinees older than age 80 years old are still underrepresented despite the prioritization of the elderly in vaccination campaigns.

Methods

We conducted a cohort study with 2 age groups, young vaccinees below the age of 60 years and elderly vaccinees over the age of 80 years, to compare their antibody responses to the first and second dose of the BNT162b2 coronavirus disease 2019 vaccination.

Results

Although the majority of participants in both groups produced specific immunoglobulin G antibody titers against SARS-CoV-2 spike protein, titers were significantly lower in elderly participants. Although the increment of antibody levels after the second immunization was higher in elderly participants, the absolute mean titer of this group remained lower than the <60 years of age group. After the second vaccination, 31.3% of the elderly had no detectable neutralizing antibodies in contrast to the younger group, in which only 2.2% had no detectable neutralizing antibodies.

Conclusions

Our data showed differences between the antibody responses raised after the first and second BNT162b2 vaccination, in particular lower frequencies of neutralizing antibodies in the elderly group. This suggests that this population needs to be closely monitored and may require earlier revaccination and/or an increased vaccine dose to ensure stronger long-lasting immunity and protection against infection.

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  1. Version published to 10.1093/cid/ciab381
  2. ScreenIT

    SciScore for 10.1101/2021.03.03.21251066: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The ethics committee of the Medical Faculty at the Heinrich-Heine University Düsseldorf, Germany (study no. 2021-1287), approved the study.
    Consent: Informed consent was obtained from all volunteers (N = 179) before sampling.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Commercially available Anti-SARS-CoV-2 tests systems: Samples were tested for Anti-SARS-CoV-2 antibodies using two commercially available test systems: Euroimmun Anti-SARS-CoV-2-QuantiVac-ELISA measuring IgG levels against SARS-CoV-2 spike S1 subunit and Abbott Architect SARS-CoV-2 IgG recognizing SARS-CoV-2 nucleocapsid (N) antibodies.
    Anti-SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    After pre-incubation, 100µl of cell suspension containing 7×104/ml Vero cells (ATTC-CCL-81) were added.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    Commercially available Anti-SARS-CoV-2 tests systems: Samples were tested for Anti-SARS-CoV-2 antibodies using two commercially available test systems: Euroimmun Anti-SARS-CoV-2-QuantiVac-ELISA measuring IgG levels against SARS-CoV-2 spike S1 subunit and Abbott Architect SARS-CoV-2 IgG recognizing SARS-CoV-2 nucleocapsid (N) antibodies.
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    The SARS-CoV-2 IgG chemiluminescent microparticle immunoassay (CMIA) from Abbott was performed on an ARCHITECT i2000 SR.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical analysis: The data were analyzed using SPSS Statistics 25 (IBM©) and GraphPad Prism 9.0.00 (
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    (GraphPad Software, San Diego, CA, USA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Simple linear regression was performed using GraphPad Prism version 9.0.0 (the coefficient of determination R2 and p-values are given in the figures).
    GraphPad Prism
    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:
    Our data presented here suggests that it might be necessary to define strategies to overcome age-related limitations for COVID-19 vaccination. Moderna has recently demonstrated an increased immune response determined by higher binding and neutralizing antibody titers by increasing the dose of the second vaccination from 25 µl to 100 µl [39]. Strategies to enhance immunogenicity such as the use of adjuvants, application of increased amounts or multiple doses of the same vaccine, or the combination of different vaccines for a heterologous prime/boost should be rapidly tested and implemented in COVID-19 vaccination protocols. Furthermore, since the majority of vaccinees did not obtain neutralizing antibody titers after the first vaccination, we suggest that postponing a second vaccination with this vaccine is neither advisable for younger nor elderly populations. This study provides insight into age-dependent limitations of immune responses elicited after the first and second dose of the BNT162b2 vaccine. By comparing similar-sized cohorts of vaccinees aged < 60 years and > 80 years, we found that more than 30% of elderly vaccinees did not attain neutralizing antibody responses after their second vaccination. Nevertheless, recent studies show that even after the first vaccination, severe courses of COVID-19 are attenuated. The elderly population is prioritized by many vaccination schedules, despite the fact that this age group is underrepresented in previous studies, and hence, ...

    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.

    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 10.1101/2021.03.03.21251066 on medRxiv