Reduced Magnitude and Durability of Humoral Immune Responses to COVID-19 mRNA Vaccines Among Older Adults

  1. Mark A Brockman
  2. Francis Mwimanzi
  3. Hope R Lapointe
  4. Yurou Sang
  5. Olga Agafitei
  6. Peter K Cheung
  7. Siobhan Ennis
  8. Kurtis Ng
  9. Simran Basra
  10. Li Yi Lim
  11. Fatima Yaseen
  12. Landon Young
  13. Gisele Umviligihozo
  14. F Harrison Omondi
  15. Rebecca Kalikawe
  16. Laura Burns
  17. Chanson J Brumme
  18. Victor Leung
  19. Julio S G Montaner
  20. Daniel Holmes
  21. Mari L DeMarco
  22. Janet Simons
  23. Ralph Pantophlet
  24. Masahiro Niikura
  25. Marc G Romney
  26. Zabrina L Brumme

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Abstract

Background

The magnitude and durability of immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines remain incompletely characterized in the elderly.

Methods

Anti-spike receptor-binding domain (RBD) antibodies, angiotensin-converting enzyme 2 (ACE2) competition, and virus neutralizing activities were assessed in plasma from 151 health care workers and older adults (range, 24–98 years of age) 1 month following the first vaccine dose, and 1 and 3 months following the second dose.

Results

Older adults exhibited significantly weaker responses than younger health care workers for all humoral measures evaluated and at all time points tested, except for ACE2 competition activity after 1 vaccine dose. Moreover, older age remained independently associated with weaker responses even after correction for sociodemographic factors, chronic health condition burden, and vaccine-related variables. By 3 months after the second dose, all humoral responses had declined significantly in all participants, and remained significantly lower among older adults, who also displayed reduced binding antibodies and ACE2 competition activity towards the Delta variant.

Conclusions

Humoral responses to COVID-19 mRNA vaccines are significantly weaker in older adults, and antibody-mediated activities in plasma decline universally over time. Older adults may thus remain at elevated risk of infection despite vaccination.

Article activity feed

  1. Version published to 10.1093/infdis/jiab592
  2. ScreenIT

    SciScore for 10.1101/2021.09.06.21263149: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Ethics approval: Written informed consent was obtained from all participants or their authorized substitute decision makers.
    IRB: This study was approved by the University of British Columbia/Providence Health Care and Simon Fraser University Research Ethics Boards (protocol H20-03906).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Vaccine-induced antibody responses against SARS-CoV-2 were assessed three ways: (1) Commercial and in-house assays to detect binding antibodies targeting the spike receptor binding domain (RBD); (2) Angiotensin-converting enzyme 2 (ACE2) competition assays to detect receptor-blocking antibodies; and (3) Neutralization assays to detect antibodies that prevent virus infection of target cells.
    Angiotensin-converting enzyme 2
    suggested: None
    ACE2
    suggested: None
    Binding antibody assays: We examined total binding antibodies against the SARS-CoV-2 N and RBD in serum using the Elecsys Anti-SARS-CoV-2 assay (which detects anti-N antibodies generated following infection) and Anti-SARS-CoV-2 S assay (which quantifies total antibodies against RBD generated following infection or vaccination), respectively, on a Cobas e601 module analyzer (Roche Diagnostics).
    anti-N
    suggested: None
    Anti-SARS-CoV-2
    suggested: None
    Bound IgG was detected using PE-conjugated anti-human IgG secondary antibody (BioLegend) with results reported as arbitrary median fluorescence intensities (MFI).
    anti-human IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were conducted using Prism v9.2.0 (GraphPad).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    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:
    A limitation of our study is that precise immune correlates of protection for SARS-CoV-2 transmission and disease severity remain incompletely characterized 32, so the implications of our results as they relate to individual-level control of COVID-19 remain uncertain. The levels of immunity induced in older adults seen here following vaccination may be sufficient to prevent symptomatic infection or severe disease in many cases, so studies linking vaccine immunogenicity data to clinical outcomes specifically among older adults are needed. Due to the timing of the vaccine rollout in British Columbia, our sample size for the durability assessments was modest; however, the weaker responses observed among LTC residents were nevertheless statistically significant. Due to small numbers of participants who received Moderna, we were unable to assess differences in responses between mRNA vaccines 14,33. Overall, our results extend a growing body of evidence indicating that COVID-19 mRNA vaccines are less immunogenic in older compared to younger adults and reveal substantial waning of immunity across all ages in the first three months following receipt of two doses of vaccine. The combined effects of lower peak immunity and natural waning of vaccine-induced responses may leave older adults at continued risk of infection by SARS-CoV-2 or its variants.

    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.
    • No funding statement was detected.
    • 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 10.1101/2021.09.06.21263149 on medRxiv