Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection

  1. Daan K. J. Pieren
  2. Sebastián G. Kuguel
  3. Joel Rosado
  4. Alba G. Robles
  5. Joan Rey-Cano
  6. Cristina Mancebo
  7. Juliana Esperalba
  8. Vicenç Falcó
  9. María J. Buzón
  10. Meritxell Genescà

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Abstract

Resident memory T cells (T RM ) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen-specific T RM are detectable beyond 11 months in the lung of convalescent COVID-19 patients, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. Here we show that the frequency of CD4 + T cells secreting IFNγ in response to S-peptides is variable but overall similar in the lung of mRNA-vaccinated patients compared to convalescent-infected patients. However, in vaccinated patients, lung responses present less frequently a T RM phenotype compared to convalescent infected individuals and polyfunctional CD107a + IFNγ + T RM are virtually absent in vaccinated patients. These data indicate that mRNA vaccination induces specific T cell responses to SARS-CoV-2 in the lung parenchyma, although to a limited extend. It remains to be determined whether these vaccine-induced responses contribute to overall COVID-19 control.

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  1. Version published to 10.1038/s41467-023-37559-w
  2. Version published to 10.1101/2022.05.25.22275300v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.05.25.22275300: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics statement: This study was performed in accordance with the Declaration of Helsinki and approved by the corresponding Institutional Review Board (PR(AG)212/2020) of the Vall d’Hebron University Hospital (HUVH), Barcelona, Spain.
    Consent: Written informed consent was provided by all patients recruited to this study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    , anti-CD3 (BV650, BD Biosciences) and anti-CD45 (BV605, BD Biosciences) antibodies.
    anti-CD3
    suggested: None
    anti-CD45
    suggested: None
    Cells were subsequently fixed and permeabilized using the FoxP3 Fix/Perm kit (BD Biosciences) and stained with anti-IL-4 (PE-Cy7, eBioscience), anti-IL-10 (PE, BD Biosciences), anti-T-bet (BV421, Biolegend) and anti-IFNγ (AF700, Invitrogen) antibodies.
    anti-IL-4
    suggested: None
    PE-Cy7
    suggested: (Bioss Cat# bs-0698R-PE-Cy7, RRID:AB_11041615)
    anti-IL-10
    suggested: None
    anti-T-bet ( BV421
    suggested: None
    anti-IFNγ
    suggested: None
    Cell surface antibody staining included anti-CD3 (Per-CP), anti-CD4 (BV605) and anti-CD56 (FITC) (all from BD Biosciences).
    anti-CD4
    suggested: None
    anti-CD56
    suggested: None
    SARS-CoV-2 serology: The serological status of patients included in this study was determined in serum samples using two commercial chemiluminescence immunoassays (CLIA) targeting specific SARS-CoV-2 antibodies: (1) Elecsys Anti-SARS-CoV-2 (Roche Diagnostics, Mannheim, Germany) was performed on the Cobas 8800 system (Roche Diagnostics, Basel, Switzerland) for the determination of total antibodies (including IgG, IgM, and IgA) against nucleocapsid (N) SARS-CoV-2 protein; and (2) Liaison SARS-CoV-2 TrimericS IgG (DiaSorin, Stillwater, MN) was performed on the LIAISON XL Analyzer (DiaSorin, Saluggia, Italy) for the determination of IgG antibodies against the spike (S) glycoprotein.
    Anti-SARS-CoV-2
    suggested: None
    IgA ) against nucleocapsid ( N
    suggested: None
    To neutralize contaminating VSV*ΔG(Luc)-G particles cells were incubated overnight in media containing 10% of the supernatant from the I1 hybridoma (ATCC CRL-2700), containing anti-VSV-G antibodies.
    anti-VSV-G
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, 293T cells were transfected with 3µg of the omicron plasmid (pcDNA3.1 omicron).
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Next day, viral particles were harvested and titrated in VeroE6 cells by enzyme luminescence assay (Britelite plus kit; PerkinElmer).
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    Statistical analyses: Flow cytometry data was analyzed using FlowJo v10.7.1 software (TreeStar).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Data and statistical analyses were performed using Prism 8.0 (GraphPad Software, La Jolla, CA, USA).
    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.
    • 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

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  4. Version published to 10.1101/2022.05.25.22275300v1 on medRxiv