Polymorphism and Selection Pressure of SARS-CoV-2 Vaccine and Diagnostic Antigens: Implications for Immune Evasion and Serologic Diagnostic Performance

  1. Eric Dumonteil
  2. Claudia Herrera

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Abstract

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6–7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well-conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.

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  1. Version published to 10.3390/pathogens9070584
  2. ScreenIT

    SciScore for 10.1101/2020.06.18.158329: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Sequence analysis: Viral genome sequences were aligned using MAFFT (11) as implemented in Geneious 11, and alignments were edited to exclude partial or low quality sequences.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    A final alignment including 17,853 quality sequences were used to construct phylogenetic trees using FastTree (12) for a global analysis of viral diversity across the world.
    FastTree
    suggested: (FastTree, RRID:SCR_015501)
    Sequence conservation across genome alignment was calculated using s sliding window of one in Geneious.
    Geneious
    suggested: (Geneious, RRID:SCR_010519)
    Finally, evolutionary selection pressures on the antigens were analyzed using the Fast, Unconstrained Bayesian AppRoximation (FUBAR), as implemented in HyPhy (15) and statistical significance was considered at a threshold of P<0.1.
    HyPhy
    suggested: (HyPhy, RRID:SCR_016162)

    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.

    About SciScore

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  3. Version published to 10.1101/2020.06.18.158329v1 on bioRxiv