Inferring MHC interacting SARS-CoV-2 epitopes recognized by TCRs towards designing T cell-based vaccines

  1. Amir Hossein Mohseni
  2. Sedigheh Taghinezhad-S
  3. Bing Su
  4. Feng Wang

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Abstract

The coronavirus disease 2019 (COVID-19) is triggered by severe acute respiratory syndrome mediated by coronavirus 2 (SARS-CoV-2) infection and was declared by WHO as a major international public health concern. While worldwide efforts are being advanced towards vaccine development, the structural modeling of TCR-pMHC (T Cell Receptor-peptide-bound Major Histocompatibility Complex) regarding SARS-CoV-2 epitopes and the design of effective T cell vaccine based on these antigens are still unresolved. Here, we present both pMHC and TCR-pMHC interfaces to infer peptide epitopes of the SARS-CoV-2 proteins. Accordingly, significant TCR-pMHC templates (Z-value cutoff > 4) along with interatomic interactions within the SARS-CoV-2-derived hit peptides were clarified. Also, we applied the structural analysis of the hit peptides from different coronaviruses to highlight a feature of evolution in SARS-CoV-2, SARS-CoV, bat-CoV, and MERS-CoV. Peptide-protein flexible docking between each of the hit peptides and their corresponding MHC molecules were performed, and a multi-hit peptides vaccine against the S and N glycoprotein of SARS-CoV-2 was designed. Filtering pipelines including antigenicity, and also physiochemical properties of designed vaccine were then evaluated by different immunoinformatics tools. Finally, vaccine-structure modeling and immune simulation of the desired vaccine were performed aiming to create robust T cell immune responses. We anticipate that our design based on the T cell antigen epitopes and the frame of the immunoinformatics analysis could serve as valuable supports for the development of COVID-19 vaccine.

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    SciScore for 10.1101/2020.09.12.294413: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Also, in order to study the atom–atom contacts, Arpeggio server was used for detailed evaluation of TCR-pMHC complex derived from SARS-CoV-2 proteins.
    Arpeggio
    suggested: (Arpeggio, RRID:SCR_010876)
    Accordingly, protein structure and visualization of the measured interactions between atoms including the strongest mutually exclusive interactions, polar contacts, H-bonds, ionic interactions, aromatic contacts, hydrophobic contacts, and carbonyl interactions were showed by WebGL-based protein structure viewer and PyMOL session based-visualization.
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    Vaccine construct was analyzed by VaxiJen v2.0 (http://www.ddg-pharmfac.net/vaxijen/VaxiJen/VaxiJen.html) with high accuracy at 0.4 thresholds for virus.
    VaxiJen
    suggested: (VaxiJen, RRID:SCR_018514)
    Also, ProtParam web server (https://web.expasy.org/protparam/) was used to predict various physicochemical properties of vaccine construct including like theoretical isoelectric point (pI), in vitro and in vivo half-life, amino acid composition, molecular weight, instability and aliphatic index, and grand average of hydropathicity (GRAVY).
    ProtParam
    suggested: (ProtParam Tool, RRID:SCR_018087)
    Indeed, I-TASSER server (https://zhanglab.ccmb.med.umich.edu/I-TASSER/), as an algorithm for fast and accurate de novo protein structure prediction, was further employed to predict the solvent accessibility, 3-dimensional structure (3D), and function of the vaccine sequence.
    I-TASSER
    suggested: (I-TASSER, RRID:SCR_014627)
    In detail, I-TASSER by recruiting SPICKER program groups all the decoys according to the pair-wise structure similarity and provides five models that are linked to the five largest structure clusters.
    SPICKER
    suggested: None
    Indeed, RAMPAGE server (http://molprobity.biochem.duke.edu/) also was used to determine the overall quality of the predicted model of the multi-hit peptides vaccine following Ramachandran plot analysis.
    http://molprobity.biochem.duke.edu/
    suggested: (MolProbity, RRID:SCR_014226)

    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.
    • 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.

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  2. Version published to 10.1101/2020.09.12.294413 on bioRxiv