Reduced Antibody Acquisition with Increasing Age following Vaccination with BNT162b2: Results from Two Longitudinal Cohort Studies in The Netherlands

  1. Lotus Leonie van den Hoogen
  2. Mardi Boer
  3. Abigail Postema
  4. Lia de Rond
  5. Mary-lène de Zeeuw-Brouwer
  6. Inge Pronk
  7. Alienke Jentien Wijmenga-Monsuur
  8. Elske Bijvank
  9. Caitlyn Kruiper
  10. Lisa Beckers
  11. Marjan Bogaard-van Maurik
  12. Ilse Zutt
  13. Jeffrey van Vliet
  14. Rianne van Bergen
  15. Marjan Kuijer
  16. Gaby Smits
  17. W. M. Monique Verschuren
  18. H. Susan J. Picavet
  19. Fiona Regina Maria van der Klis
  20. Gerco den Hartog
  21. Robert Samuel van Binnendijk
  22. Anne-Marie Buisman

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Abstract

Vaccine-induced protection against severe COVID-19, hospitalization, and death is of the utmost importance, especially in the elderly. However, limited data are available on humoral immune responses following COVID-19 vaccination in the general population across a broad age range. We performed an integrated analysis of the effect of age, sex, and prior SARS-CoV-2 infection on Spike S1-specific (S1) IgG concentrations up to three months post-BNT162b2 (Pfizer/BioNTech; Comirnaty) vaccination. In total, 1735 persons, eligible for COVID-19 vaccination through the national program, were recruited from the general population (12 to 92 years old). Sixty percent were female, and the median vaccination interval was 35 days (interquartile range, IQR: 35–35). All participants had seroconverted to S1 one month after two vaccine doses. S1 IgG was higher in participants with a history of SARS-CoV-2 infection (median: 4535 BAU/mL, IQR: 2341–7205) compared to infection-naive persons (1842 BAU/mL, 1019–3116), p < 0.001. In infection-naive persons, linear mixed effects regression showed a strong negative association between age and S1 IgG (p < 0.001) across the entire age range. Females had higher S1 IgG than males (p < 0.001). In persons with an infection history, age nor sex was associated with S1 IgG concentrations. The lower magnitude of S1 antibodies in older persons following COVID-19 vaccination will affect long-term protection.

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  1. Version published to 10.3390/vaccines10091480
  2. ScreenIT

    SciScore for 10.1101/2022.05.18.22275209: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics statement: Ethical approval was obtained through The Medical Research Ethics Committee Utrecht for both the 50+ population cohort (NL74843.041.21, EudraCT: 2021-001976-40), and for the adolescent and adult cohort (12-60 years) (NL76440.041.21, EudraCT: 2021-001357-31).
    Consent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    RandomizationA linear mixed effects regression model with a random intercept per participant was used to determine the effect of timepoint, age and sex on S1 IgG concentrations using lme4 (version 1.1.28 [17]).
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: Persons with serological evidence of a SARS-CoV-2 infection history (i.e., seropositive to Spike S1 at Pre-vacc) and/or a self-reported positive SARS-CoV-2 test performed by local health authorities prior to their vaccination schedule were analysed separately.

    Table 2: Resources

    Antibodies
    SentencesResources
    Immunoglobulin G detection: Total immunoglobulin G (IgG) antibody concentrations to Spike S1 and Nucleoprotein were measured simultaneously using a bead-based assay as previously described [12].
    Total immunoglobulin G (IgG
    suggested: None
    IgG concentrations were expressed as binding antibody units per mL (BAU/ml) using 5-parameter logistic interpolation of the International Standard for human anti-SARS-CoV-2 immunoglobulin (20/136 NIBSC standard) [13].
    anti-SARS-CoV-2 immunoglobulin
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses: All statistical analyses were performed in RStudio (version 4.1.3) [16].
    RStudio
    suggested: (RStudio, RRID:SCR_000432)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

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  3. Version published to 10.1101/2022.05.18.22275209v1 on medRxiv