A vaccine built from potential immunogenic pieces derived from the SARS-CoV-2 spike glycoprotein

  1. Jose Marchan

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Abstract

Coronavirus Disease 2019 (COVID-19) represents a new global threat demanding a multidisciplinary effort to fight its etiological agent—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this regard, immunoinformatics may aid to predict prominent immunogenic regions from critical SARS-CoV-2 structural proteins, such as the spike (S) glycoprotein, for their use in prophylactic or therapeutic interventions against this rapidly emerging coronavirus. Accordingly, in this study, an integrated immunoinformatics approach was applied to identify cytotoxic T cell (CTC), T helper cell (THC), and Linear B cell (BC) epitopes from the S glycoprotein in an attempt to design a high-quality multi-epitope vaccine. The best CTC, THC, and BC epitopes showed high viral antigenicity, lack of allergenic or toxic residues, and suitable HLA-viral peptide interactions. Remarkably, SARS-CoV-2 receptor-binding domain (RBD) and its receptor-binding motif (RBM) harbour several potential epitopes. The structure prediction, refinement, and validation data indicate that the multi-epitope vaccine has an appropriate conformation and stability. Three conformational epitopes and an efficient binding between Toll-like receptor 4 (TLR4) and the vaccine model were observed. Importantly, the population coverage analysis showed that the multi-epitope vaccine could be used globally. Notably, computer-based simulations suggest that the vaccine model has a robust potential to evoke and maximize both immune effector responses and immunological memory to SARS-CoV-2. Further research is needed to accomplish with the mandatory international guidelines for human vaccine formulations.

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    SciScore for 10.1101/2020.09.24.312355: (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 cell-mediated response is mainly based on the clonal expansion of human leukocyte antigen (HLA) class I-restricted CD8+ cytotoxic T cells (CTC), which are critical to antiviral defence during acute infection, and HLA class II-restricted CD4+ T helper cells (THC), which are necessary for the generation of specific antiviral antibodies when they crosstalk with B cells (BC) [18].
    antiviral defence during acute infection,
    suggested: None
    Software and Algorithms
    SentencesResources
    The complete amino acid sequence of the SARS-CoV-2 S glycoprotein was retrieved from Uniprot (http://www.uniprot.org/) in FASTA format (accession number: P0DTC2).
    http://www.uniprot.org/
    suggested: (Universal Protein Resource, RRID:SCR_002380)

    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: We detected the following sentences addressing limitations in the study:
    Immunoinformatics represents a valuable tool whereby the limitations in the selection of appropriate antigens and immunodominant epitopes may be overcome [17]. Previous in silico-based reports have shown that the SARS-CoV-2 S glycoprotein contains potential epitopes [8-11]. Therefore, researchers have recently attempted to design epitope-based vaccine candidates against SARS-CoV-2 [10, 11]. Despite these relevant contributions, one group only used T cell epitopes and did not include BC epitopes [10], which are fundamental players in antiviral immune response [18]. The second work, on the other hand, considered several viral membrane proteins, including the S glycoprotein, to identified probable T and BC epitopes [11]. Although the predicted epitopes showed good immunogenic potential, the vaccine does not target S glycoprotein RBM [11]. In the present study, highly potential B and T cell epitopes from the SARS-CoV-2 glycoprotein were predicted and the best selected to design a high-quality multi-epitope vaccine candidate. Remarkably, this vaccine harbours 2 epitopes (E19 in Table 1 and E10 in Table 2) that could evoke immune responses against SARS-CoV-2 RBM—the main responsible for virus entry into human cells [4,51], whereas 4 epitopes (E43, E44, E45, and E46 in Table 1) may direct the immune attack against other regions of SARS-CoV-2 RBD. These results are consistent with in vitro data that have demonstrated the antigenicity of the SARS-CoV-2 S glycoprotein [4]. The T cell e...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT01609257CompletedNorovirus Bivalent-Vaccine Efficacy Study

    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.

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  2. Version published to 10.1101/2020.09.24.312355 on bioRxiv