Immuno-informatics design of a multimeric epitope peptide based vaccine targeting SARS-CoV-2 spike glycoprotein

  1. Onyeka S. Chukwudozie
  2. Clive M. Gray
  3. Tawakalt A. Fagbayi
  4. Rebecca C. Chukwuanukwu
  5. Victor O. Oyebanji
  6. Taiwo T. Bankole
  7. Richard A. Adewole
  8. Eze M. Daniel

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Abstract

Developing an efficacious vaccine for SARS-CoV-2 infection is critical to stemming COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in designing an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers and 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC I and II alleles, respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. With our In silico test, the vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was also characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We, therefore, propose that potential vaccine designs consider this approach.

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  1. Version published to 10.1371/journal.pone.0248061
  2. ScreenIT

    SciScore for 10.1101/2020.07.30.228221: (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
    Therefore, the DiscoTope server was used to predict the surface accessibility and amino acids that form discontinuous B cell epitopes found from X-ray crystallography of antigen/antibody protein buildings.
    DiscoTope
    suggested: (DiscoTope, RRID:SCR_018530)
    Antigenicity testing was conducted through the Vaxijen v2.0 server (http://www.ddgpharmfac.net/vaxijen/VaxiJen/VaxiJen.html) [20], which operate based on auto- and cross-covariance transformation of the input protein sequence into uniform vectors of principal amino acid properties.
    Vaxijen
    suggested: (VaxiJen, RRID:SCR_018514)
    The PSIPRED v4.0 server was adopted for the prediction of the vaccine’s secondary structure [28], while the Swiss dock online tool was used for the tertiary structure prediction of both the vaccine construct and the human HLA class II histocompatibility antigen, DR alpha chain.
    PSIPRED
    suggested: (PSIPRED, RRID:SCR_010246)
    UCSF Chimera and Pymol tools were utilized to produce figures of docked complexes.
    Pymol
    suggested: (PyMOL, RRID:SCR_000305)
    The obtained refined nucleotide was cloned into the pET28a (+) vector, utilizing the SnapGene 4.2 tool.
    SnapGene
    suggested: (SnapGene, RRID:SCR_015052)

    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 page 38. 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.

    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. ScreenIT

    SciScore for 10.1101/2020.07.30.228221: (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

    Antibodies
    SentencesResources
    The observed increase in immunoglobin activities involving the combination of IgG1 + IgG2, IgG + IgM and IgM antibodies components, was another evidence that the vaccine stimulated a good immune response [Figure 8a].
    IgG1 + IgG2
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>IgG + IgM</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>IgM antibodies components</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>IgM</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Therefore, the DiscoTope server was used to predict the surface accessibility and amino acids that form discontinuous B cell epitopes found from X-ray crystallography of antigen/antibody protein buildings.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>DiscoTope</b></div>
        <div>suggested: (DiscoTope, <a href="https://scicrunch.org/resources/Any/search?q=SCR_018530">SCR_018530</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Antigenicity testing was conducted through the Vaxijen v2.0 server (http://www.ddgpharmfac.net/vaxijen/VaxiJen/VaxiJen.html) [20], which operate based on auto- and cross-covariance transformation of the input protein sequence into uniform vectors of principal amino acid properties.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Vaxijen</b></div>
        <div>suggested: (VaxiJen, <a href="https://scicrunch.org/resources/Any/search?q=SCR_018514">SCR_018514</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">The PSIPRED v4.0 server was adopted for the prediction of the vaccine’s secondary structure [28], while the Swiss dock online tool was used for the tertiary structure prediction of both the vaccine construct and the human HLA class II histocompatibility antigen, DR alpha chain.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>PSIPRED</b></div>
        <div>suggested: (PSIPRED, <a href="https://scicrunch.org/resources/Any/search?q=SCR_010246">SCR_010246</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">UCSF Chimera and Pymol tools were utilized to produce figures of docked complexes.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Pymol</b></div>
        <div>suggested: (PyMOL, <a href="https://scicrunch.org/resources/Any/search?q=SCR_000305">SCR_000305</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">The obtained refined nucleotide was cloned into the pET28a (+) vector, utilizing the SnapGene 4.2 tool.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>SnapGene</b></div>
        <div>suggested: (SnapGene, <a href="https://scicrunch.org/resources/Any/search?q=SCR_015052">SCR_015052</a>)</div>
      </div>
    </td></tr></table>

    Data from additional tools added to each annotation on a weekly basis.

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.30.228221v1 on bioRxiv