Older Adults Mount Less Durable Humoral Responses to Two Doses of COVID-19 mRNA Vaccine but Strong Initial Responses to a Third Dose

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

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

Third coronavirus disease 2019 (COVID-19) vaccine doses are broadly recommended, but immunogenicity data remain limited, particularly in older adults.

Methods

We measured circulating antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, ACE2 displacement, and virus neutralization against ancestral and omicron (BA.1) strains from prevaccine up to 1 month following the third dose, in 151 adults aged 24–98 years who received COVID-19 mRNA vaccines.

Results

Following 2 vaccine doses, humoral immunity was weaker, less functional, and less durable in older adults, where a higher number of chronic health conditions was a key correlate of weaker responses and poorer durability. One month after the third dose, antibody concentrations and function exceeded post–second-dose levels, and responses in older adults were comparable in magnitude to those in younger adults at this time. Humoral responses against omicron were universally weaker than against the ancestral strain after both the second and third doses. Nevertheless, after 3 doses, anti-omicron responses in older adults reached equivalence to those in younger adults. One month after 3 vaccine doses, the number of chronic health conditions, but not age, was the strongest consistent correlate of weaker humoral responses.

Conclusions

Results underscore the immune benefits of third COVID-19 vaccine doses, particularly in older adults.

Article activity feed

  1. Version published to 10.1093/infdis/jiac199
  2. Version published to 10.1101/2022.01.06.22268745v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.01.06.22268745: (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 decision makers.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Our cohort of 151 individuals included 81 healthcare workers (HCW) and 56 older adults (including 18 residents of long-term care or assisted living facilities) who were COVID-19 naive at study entry, and 14 COVID-19 convalescent individuals (including 8 HCW and 6 older adults), where prior COVID-19 was determined by the presence of anti-SARS-CoV-2 N antibodies at study entry (see below).
    anti-SARS-CoV-2 N
    suggested: None
    Binding antibody assays: We measured total binding antibodies against SARS-CoV-2 nucleocapsid (N) and spike (S) RBD in serum using the Roche Elecsys Anti-SARS-CoV-2 and Anti-SARS-CoV-2 S assays, respectively, on a Cobas e601 module analyzer (Roche Diagnostics).
    SARS-CoV-2 nucleocapsid (N)
    suggested: None
    Anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were conducted using Microsoft Excel and Prism v9.2.0 (GraphPad).
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)
    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:
    Our study has several limitations. As the precise immune correlates of protection for SARS-CoV-2 transmission and disease severity remain incompletely characterized 42, the implications of our results on individual-level protection from SARS-CoV-2 infection and COVID-19 remain uncertain. We did not investigate vaccine-induced T-cell responses, which may play critical roles in protection against severe COVID-19, particularly in the context of variants 43–50. Furthermore, our assays tested only the ancestral SARS-CoV-2 strain (Wuhan or USA-WA1/2020); assessments of SARS-CoV-2 variants including Omicron are in progress. Our study was not designed nor powered to investigate potential differences in immune responses between the two mRNA vaccines 51,52. Finally, at the time of writing, post-third dose data were available for only a subset of participants, and at a single time point. In conclusion, while the observation of strong binding and neutralizing antibody responses to third COVID-19 vaccine doses in older adults, including residents of long-term care, are encouraging, it will be important to closely monitor the decline in these responses over time in this population.

    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.

  4. Version published to 10.1101/2022.01.06.22268745v1 on medRxiv