Expansion of tissue-resident CD8+ T cells and CD4+ Th17 cells in the nasal mucosa following mRNA COVID-19 vaccination

  1. Aloysious Ssemaganda
  2. Huong Mai Nguyen
  3. Faisal Nuhu
  4. Naima Jahan
  5. Catherine M. Card
  6. Sandra Kiazyk
  7. Giulia Severini
  8. Yoav Keynan
  9. Ruey-Chyi Su
  10. Hezhao Ji
  11. Bernard Abrenica
  12. Paul J. McLaren
  13. T. Blake Ball
  14. Jared Bullard
  15. Paul Van Caeseele
  16. Derek Stein
  17. Lyle R. McKinnon

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Abstract

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the upper respiratory tract, remains lacking. We enumerated and phenotyped T cells in nasal mucosa and blood before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n =21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ expanded ∼12 days following the first and second doses, by 0.31 and 0.43 log 10 cells per swab respectively (p=0.058 and p=0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decreased post-vaccination. Similar increases in nasal CD8+CD69+CD103-T cells were observed, particularly following the second dose. CD4+ Th17 cells were also increased in abundance following both doses. Following stimulation with SARS-CoV-2 spike peptides, CD8+ T cells increased expression of CD107a and CD154. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.07.442971: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study participants and ethics board approval: Study volunteers (n=29) included staff enrolled at the Cadham Provincial Laboratory in Winnipeg, with ethics approval from the University of Manitoba Health Research Ethics Board (HREB) and the Public Health Agency of Canada (PHAC).
    Consent: Informed consent was obtained and a comprehensive socio-demographic and health assessment questionnaire administered to all study participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    FlowSOM algorithm (Version 2.6) was used to create cluster populations from the dimensionally reduced data based on their similarity and subsequently segregated based on relative abundance and phenotype using ClusterExplorer (Version 1.5.9).
    FlowSOM
    suggested: (FlowSOM, RRID:SCR_016899)
    ClusterExplorer
    suggested: None
    Freshly isolated nasal cells from (n=11) were stimulated for six hours at 37 °C / 5% CO2 with SARS–CoV-2 spike peptide pools S, S1 and S+ containing 15-mer sequences overlapping by11 amino acids (PepTivator®, Miltenyi Biotec), encompassing the complete spike protein sequence (GenBank MN908947.3) at a final concentration of 1µg/mL per peptide, in the presence of Golgi-Plug (BD Biosciences), Golgi-Stop (BD Biosciences) and anti–CD107a (clone H4A3, BD Biosciences).
    BD Biosciences
    suggested: (BD Biosciences, RRID:SCR_013311)
    Cells were then washed, acquired using a BDLSR Fortessa (BD Biosciences) and analyzed using FlowJo™ version 10.7.1 (Becton Dickinson Life Sciences).
    FlowJo™
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analyses were performed using SPSS v.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    27.0 while all the graphing and was performed using Prism version 9 (GraphPad Software, LLC).
    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 10. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  2. Version published to 10.1101/2021.05.07.442971v1 on bioRxiv