SARS‐CoV‐2 spike glycoprotein‐reactive T cells can be readily expanded from COVID‐19 vaccinated donors

  1. Pavla Taborska
  2. Jan Lastovicka
  3. Dmitry Stakheev
  4. Zuzana Strizova
  5. Jirina Bartunkova
  6. Daniel Smrz

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Introduction

The COVID‐19 vaccine was designed to provide protection against infection by the severe respiratory coronavirus 2 (SARS‐CoV‐2) and coronavirus disease 2019 (COVID‐19). However, the vaccine's efficacy can be compromised in patients with immunodeficiencies or the vaccine‐induced immunoprotection suppressed by other comorbidity treatments, such as chemotherapy or immunotherapy. To enhance the protective role of the COVID‐19 vaccine, we have investigated a combination of the COVID‐19 vaccination with ex vivo enrichment and large‐scale expansion of SARS‐CoV‐2 spike glycoprotein‐reactive CD4 + and CD8 + T cells.

Methods

SARS‐CoV‐2‐unexposed donors were vaccinated with two doses of the BNT162b2 SARS‐CoV‐2 vaccine. The peripheral blood mononuclear cells of the vaccinated donors were cell culture‐enriched with T cells reactive to peptides derived from SARS‐CoV‐2 spike glycoprotein. The enriched cell cultures were large‐scale expanded using the rapid expansion protocol (REP) and the peptide‐reactive T cells were evaluated.

Results

We show that vaccination with the SARS‐CoV‐2 spike glycoprotein‐based mRNA COVID‐19 vaccine‐induced humoral response against SARS‐CoV‐2 spike glycoprotein in all tested healthy SARS‐CoV‐2‐unexposed donors. This humoral response was found to correlate with the ability of the donors' PBMCs to become enriched with SARS‐CoV‐2 spike glycoprotein‐reactive CD4 + and CD8 + T cells. Using an 11‐day REP, the enriched cell cultures were expanded nearly 1000‐fold, and the proportions of the SARS‐CoV‐2 spike glycoprotein‐reactive T cells increased.

Conclusion

These findings show for the first time that the combination of the COVID‐19 vaccination and ex vivo T cell large‐scale expansion of SARS‐CoV‐2‐reactive T cells could be a powerful tool for developing T cell‐based adoptive cellular immunotherapy of COVID‐19.

Article activity feed

  1. Version published to 10.1002/iid3.496
  2. ScreenIT

    SciScore for 10.1101/2021.05.27.446089: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Each donor provided signed written informed consent for the use of their blood-derived products for future research and all experimental protocols were approved by the ethical standards of the institutional research committee – the Ethics Committee of the University Hospital Motol in Prague, and performed in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
    IRB: Each donor provided signed written informed consent for the use of their blood-derived products for future research and all experimental protocols were approved by the ethical standards of the institutional research committee – the Ethics Committee of the University Hospital Motol in Prague, and performed in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Microblot array: The collected donors’ sera were analyzed for the presence of multiple antigen-specific antibodies using Microblot-Array COVID-19 IgG, IgA, or IgM kits (TestLine Clinical Diagnostics, Brno, Czech Republic).
    antigen-specific
    suggested: None
    The IgG, IgA, and IgM antibodies against the following antigens were determined: SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) and S2 domain (S2), SARS-CoV-2 nucleocapsid protein (NCP), E protein (EP), and papain-like protease (PLP), Middle East respiratory syndrome-related coronavirus (MERS-CoV) spike glycoprotein S1 subunit (S1), SARS-CoV NCP, human coronavirus 229E (HuCoV 229E) NCP, human angiotensin-converting enzyme (ACE-2)
    SARS-CoV-2 spike glycoprotein receptor-binding domain ( RBD )
    suggested: None
    S2
    suggested: None
    SARS-CoV-2 nucleocapsid protein ( NCP)
    suggested: None
    MERS-CoV ) spike glycoprotein S1 subunit ( S1
    suggested: None
    The cells were transferred to a V-bottom 96-well plate (Nalgene) and stained as described [29] with live/dead fixable stain and the following antibodies: CD4-PE-Cy7 and CD8-Alexa Fluor 700 (Exbio, Prague, Czech Republic), CD3-PerCP-Cy5.5, TNFα-APC, and IFNγ-PE (Becton Dickinson, Franklin Lakes, NJ).
    CD8-Alexa
    suggested: (MBL International Cat# D271-A64, RRID:AB_10794611)
    Software and Algorithms
    SentencesResources
    The cells were analyzed by FACSAria II (Becton Dickinson, Heidelberg, Germany) and the data processed by FlowJo software (Tree Star, Ashland, OR).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical Analysis: The means of values±SEM were calculated from the indicated sample size (n) using GraphPad Prism 6 (GraphPad Software, La Jolla, CA) and the statistical significance (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001) between two groups of samples determined by Wilcoxon matched-pair signed-rank tests and between three or more groups the statistical significance was determined by matched-pair 1-way ANOVA with Dunn’s post test.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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 pages 29 and 30. 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.
    • 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 10.1101/2021.05.27.446089v1 on bioRxiv