Weak humoral immune reactivity among residents of long-term care facilities following one dose of the BNT162b2 mRNA COVID-19 vaccine

  1. Mark A. Brockman
  2. Francis Mwimanzi
  3. Yurou Sang
  4. Kurtis Ng
  5. Olga Agafitei
  6. Siobhan Ennis
  7. Hope Lapointe
  8. Landon Young
  9. Gisele Umviligihozo
  10. Laura Burns
  11. Chanson Brumme
  12. Victor Leung
  13. Julio S.G. Montaner
  14. Daniel Holmes
  15. Mari DeMarco
  16. Janet Simons
  17. Masa Niikura
  18. Ralph Pantophlet
  19. Marc G. Romney
  20. Zabrina L. Brumme

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Abstract

Background

Several Canadian provinces are extending the interval between COVID-19 vaccine doses to increase population vaccine coverage more rapidly. However, immunogenicity of these vaccines after one dose is incompletely characterized, particularly among the elderly, who are at greatest risk of severe COVID-19.

Methods

We assessed SARS-CoV-2 humoral responses pre-vaccine and one month following the first dose of BNT162b2 mRNA vaccine, in 12 COVID-19 seronegative residents of long-term care facilities (median age, 82 years), 18 seronegative healthcare workers (HCW; median age, 36 years) and 4 convalescent HCW. Total antibody responses to SARS-CoV-2 nucleocapsid (N) and spike protein receptor binding domain (S/RBD) were assessed using commercial immunoassays. We quantified IgG and IgM responses to S/RBD and determined the ability of antibodies to block S/RBD binding to ACE2 receptor using ELISA. Neutralizing antibody activity was also assessed using pseudovirus and live SARS-CoV-2.

Results

After one vaccine dose, binding antibodies against S/RBD were ∼4-fold lower in residents compared to HCW (p<0.001). Inhibition of ACE2 binding was 3-fold lower in residents compared to HCW (p=0.01) and pseudovirus neutralizing activity was 2-fold lower (p=0.003).While six (33%) seronegative HCW neutralized live SARS-CoV-2, only one (8%) resident did (p=0.19). In contrast, convalescent HCW displayed 7- to 20-fold higher levels of binding antibodies and substantial ability to neutralize live virus after one dose.

Interpretation

Extending the interval between COVID-19 vaccine doses may pose a risk to the elderly due to lower vaccine immunogenicity in this group. We recommend that second doses not be delayed in elderly individuals.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.17.21253773: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Ethics approval: Written informed consent was obtained from all participants.
    IRB: This study was approved by the University of British Columbia/Providence Health Care and Simon Fraser University Research Ethics Boards (protocol H20-03906).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableResidents were predominantly male (58%) and a median 82 years of age, while seronegative HCW were predominantly female (72%) and a median of 36 years of age.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Total binding antibodies in serum against the SARS-CoV-2 nucleocapsid (N) and spike protein receptor binding domain (S/RBD) were determined using the Roche Elecsys Anti-SARS-CoV-2 and Anti-SARS-CoV-2 S assays, respectively, on a cobas e 601 module analyzer (Roche Diagnostics).
    Anti-SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    NAbs were determined using pseudovirus and live SARS-CoV-2 infectivity assays employing VeroE6-TMPRSS2 cells (JCRB-1818) as targets.
    VeroE6-TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Pseudotyped virions were generated by co-transfecting 293T cells (ATCC) with a plasmid encoding SARS-CoV-2 Wuhan-Hu-1 Spike glycoprotein (Genscript) or VSV-G Indiana glycoprotein control (pHEF-VSV-G; NIH HIV Reagent Program) along with a lentiviral packaging plasmid (pCMV-dR8.2 dvpr 17 ; Addgene) and luciferase expression plasmid (pLenti CMV Puro LUC (w168-1) 18 ; Addgene).
    293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were conducted using Prism v9.0.2 (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: 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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2021.03.17.21253773v1 on medRxiv