Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2)

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Abstract

A new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19 + cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-γ-secreting lymphocytes in CD4 + or CD8 + cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-γ-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides.

Importance

So far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.

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  1. SciScore for 10.1101/2020.03.03.962332: (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
    Next the plates were washed with PBS and again incubated at 37 °C for 2 h with horseradish peroxidase conjugated Goat Anti-mouse IgG antibody (1:5000; Genscript, Nanjing, China).
    Anti-mouse IgG
    suggested: (LSBio (LifeSpan Cat# LS-C69682-5000, RRID:AB_1653096)
    APC-conjugated anti-mouse CD19 antibody (Biolegend, San Diego, US),
    anti-mouse CD19
    suggested: None
    PerCP/Cyanine5.5-conjugated anti-mouse CD95 (Fas) antibody (Biolegend, San Diego, US) and FITC-conjugated anti-mouse GL7 antibody (Biolegend, San Diego, US).
    PerCP/Cyanine5.5-conjugated anti-mouse CD95 ( Fas ) antibody ( Biolegend , San Diego , US )
    suggested: None
    anti-mouse CD95
    suggested: None
    Fas
    suggested: None
    anti-mouse CD8a antibody (Biolegend, San Diego, US),
    CD8a
    suggested: None
    d anti-mouse CD4 antibody (Biolegend, San Diego, US) and APC-conjugated anti-mouse IFN-γ antibody (Biolegend, San Diego, US).
    anti-mouse CD4
    suggested: None
    anti-mouse IFN-γ
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    The immunization experiment constituted three groups, each consisting of 12 6–8 week-old female C57mice.
    C57mice
    suggested: None
    Software and Algorithms
    SentencesResources
    Data retrieval: The genome sequence of SARS-CoV-2 isolate Wuhan-Hu-1 was retrieved from the NCBI database under the accession number MN908947.
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    All predicted structures or models were decorated and displayed by the open source version of pymol program (
    pymol
    suggested: (PyMOL, RRID:SCR_000305)

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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