SARS -CoV-2 T-cell immunity to variants of concern following vaccination

  1. Kathleen M.E. Gallagher
  2. Mark B. Leick
  3. Rebecca C. Larson
  4. Trisha R. Berger
  5. Katelin Katsis
  6. Jennifer Y. Yam
  7. Gabrielle Brini
  8. Korneel Grauwet
  9. MGH COVID-19 Collection & Processing Team
  10. Marcela V. Maus

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Abstract

Recently, two mRNA vaccines to severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) have become available, but there is also an emergence of SARS-CoV-2 variants with increased transmissibility and virulence 1–6 . A major concern is whether the available vaccines will be equally effective against these variants. The vaccines are designed to induce an immune response against the SARS-CoV-2 spike protein 7, 8 , which is required for viral entry to host cells 9 . Immunity to SARS-CoV-2 is often evaluated by antibody production, while less is known about the T-cell response. Here we developed, characterized, and implemented two standardized, functional assays to measure T-cell immunity to SARS-CoV-2 in uninfected, convalescent, and vaccinated individuals. We found that vaccinated individuals had robust T-cell responses to the wild type spike and nucleocapsid proteins, even more so than convalescent patients. We also found detectable but diminished T-cell responses to spike variants (B.1.1.7, B.1.351, and B.1.1.248) among vaccinated but otherwise healthy donors. Since decreases in antibody neutralization have also been observed with some variants 10–12 , investigation into the T-cell response to these variants as an alternative means of viral control is imperative. Standardized measurements of T-cell responses to SARS-CoV-2 are feasible and can be easily adjusted to determine changes in response to variants.

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    SciScore for 10.1101/2021.05.03.442455: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Protocols were approved by the Partners Institutional Review Board.
    Sex as a biological variableConvalescent cohort: We tested 25 individuals (9 males, 16 females) who had recovered from COVID-19 between March and May 2020.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    A result of <1.0 is interpreted as negative for anti-spike antibodies, and a result of ≥1.0 is interpreted as positive for anti-spike antibodies.
    anti-spike
    suggested: None
    Software and Algorithms
    SentencesResources
    Selection of ELISpot SFU threshold for positivity: Receiver operator characteristic (ROC) curve analysis was performed in Prism V8.0 (GraphPad Software Inc) using the unvaccinated donors with no known history of SARS-CoV-2 infection or contact with known infected individuals (healthy controls), alongside the 25 convalescent patients.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    The clinical specificity of this assay is reported to be 98.4% [95% CI, 96.6–99.3%], and sensitivity 94.7% [95% CI, 90.9–97.2%].2 Variant modeling: Spike protein was modeled using Pymol version 2.4.1 and the protein data bank trimeric spike protein structure 7DX0 in which one of the spike monomers’ receptor binding domains adopts the “up” conformation3.
    Pymol
    suggested: (PyMOL, RRID:SCR_000305)
    Statistical analysis: Statistical analysis was performed using Prism V8.0 (GraphPad Software Inc).
    Prism
    suggested: (PRISM, RRID:SCR_005375)

    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

    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 10.1101/2021.05.03.442455 on bioRxiv