A Glimpse into the Diverse Cellular Immunity against SARS-CoV-2

  1. Cheng-Wei Chang
  2. Yuchen Liu
  3. Cheng Jiao
  4. Hongwei Liu
  5. Jie Gong
  6. Xiaochuan Chen
  7. Lung-Ji Chang

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response has been shown to play a critical role in preventing severe illness or death in patients infected with SARS-CoV-2 or its variants. Given the multiple T-cell epitopes shared by wild-type virus and its variants, we hypothesized that vaccines that target multiple T-cell epitopes of SARS-CoV-2 may provide a “universal protection” against the wild-type virus as well as its variants, even the heavily mutated ones. To test this, we assessed SARS-CoV-2-specific T-cell precursors in healthy individuals using overlapping peptide pools of SARS-CoV-2 structural and functional proteins, including spike (S), membrane (M), envelope (E), nucleocapsid (N), and protease (P) proteins as target antigens. Diverse T-cell precursor frequencies specific to these viral antigens were detected in healthy individuals, including high, medium, low, and no responders. This was further confirmed by efficient induction of anti-SARS-CoV-2 T-cell immune responses using ex vivo dendritic cell (DC)/T cell coculture. The results demonstrated T-cell responses consistent with the precursor frequencies of each of the individuals tested. Importantly, the combination of all five viral peptide pools induced the strongest cellular immune response, and further, after a DC-peptides re-stimulation, even the no responders developed an increased anti-viral T-cell response. These analyses recapitulate the presence of a broad anti-SARS-CoV-2 cellular immunity even in an immune naïve population, which could be enhanced by antigen presenting cells presenting the overlapping antigenic peptides. Given the critical role of cellular immunity in COVID-19 protection, these results have important implications for vaccine design and immunotherapy in fighting SARS-CoV-2 and its variants.

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  1. Version published to 10.3390/vaccines9080827
  2. ScreenIT

    SciScore for 10.1101/2021.02.17.431750: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Blood donors and PBMC isolation: Healthy donors’ blood specimens were obtained with approval from the Institutional Review Board (IRB) of Shenzhen Geno-Immune Medical Institute (GIMI IRB-20001 and IRB-20002) with informed consent from participants in accordance with regulatory guidelines.
    Consent: Blood donors and PBMC isolation: Healthy donors’ blood specimens were obtained with approval from the Institutional Review Board (IRB) of Shenzhen Geno-Immune Medical Institute (GIMI IRB-20001 and IRB-20002) with informed consent from participants in accordance with regulatory guidelines.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Monensin A (Sigma-Aldrich) and FITC-conjugated Abs for CD107a or isotype matched antibodies (BD Pharmingen, San Diego, CA, USA) were added 1 hour after stimulation and incubated for 5 hours.
    CD107a
    suggested: None
    Cells were then stained with antibodies against CD3, CD8, and CD4 and fixed, permeabilized with Cytofix/Cytoperm solution and stained with antibodies against IFN-γ, TNFα and IL-2 (all from BD Pharmingen) at 4°C for 20 min.
    CD3
    suggested: None
    CD8
    suggested: None
    CD4
    suggested: None
    antibodies against IFN-γ
    suggested: None
    TNFα
    suggested: None
    IL-2
    suggested: None
    Software and Algorithms
    SentencesResources
    The spots in the plate were quantified using the Bio Reader 400 Pro-X and analyzed in Excel as instructed with standard error.
    Excel
    suggested: None

    Results from OddPub: Thank you for sharing your data.

    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

    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 10.1101/2021.02.17.431750v1 on bioRxiv
  4. Version published to 10.21203/rs.3.rs-77845/v1 on Research Square