Algorithm for the Quantitation of Variants of Concern for Rationally Designed Vaccines Based on the Isolation of SARS-CoV-2 Hawaiʻi Lineage B.1.243

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Abstract

SARS-CoV-2 worldwide emergence and evolution has resulted in variants containing mutations resulting in immune evasive epitopes that decrease vaccine efficacy. We acquired clinical samples, analyzed SARS-CoV-2 genomes, used the most worldwide emerged spike mutations from Variants of Concern/Interest, and developed an algorithm for monitoring the SARS-CoV-2 vaccine platform. The algorithm partitions logarithmic-transformed prevalence data monthly and Pearson’s correlation determines exponential emergence. The SARS-CoV-2 genome evaluation indicated 49 mutations. Nine of the ten most worldwide prevalent (>70%) spike protein changes have r- values >0.9. The tenth, D614G, has a prevalence >99% and r -value of 0.67. The resulting algorithm is based on the patterns these ten substitutions elucidated. The strong positive correlation of the emerged spike protein changes and algorithmic predictive value can be harnessed in designing vaccines with relevant immunogenic epitopes. SARS-CoV-2 is predicted to remain endemic and continues to evolve, so must SARS-CoV-2 monitoring and next-generation vaccine design.

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  1. SciScore for 10.1101/2021.08.18.455536: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingAfter observing significant CPE at 48 hours, supernatant was blind passaged three times in the Vero E6 cells.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    After observing significant CPE at 48 hours, supernatant was blind passaged three times in the Vero E6 cells.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Briefly, on the day of the assay, DMEM in 10% FBS was removed from wells with Vero cells, wells were washed twice with serum-free DMEM, and inoculated with multiplicity of infection (MOI) 0.1 and 1 virus isolates diluted in 500 µL DMEM in 2% FBS and incubated at 37°C and 5% CO2 for two hours.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    All qRT-PCR and Genomic Equivalence data were analyzed and visualized using GraphPad Prism 9 Version 9.2.0.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    WGS was conducted by the ASGPB Core, UHM.
    WGS
    suggested: None
    Trimmed result quality was confirmed with FASTQC.
    FASTQC
    suggested: (FastQC, RRID:SCR_014583)
    The trimmed-paired-end reads were then mapped to the NC_045512 reference genome using Bowtie223 and variants called with samtools mpileup24 and transformed from VCF to FASTQ using bcftools and vcfutils25 and finally converted to FASTA using seqtk.
    samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    The SNPs were inputted into the SnapGene sequence feature and Nextclade45 to determine amino acid substitutions (AAS).
    SnapGene
    suggested: (SnapGene, RRID:SCR_015052)
    14 Pearson’s was calculated using RStudio version 1.3.1093 (R version 4.0.3) and plotted with the ggplot2 package.
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    Separately, the following search parameter was used in PubMed to locate in silico studies predicting vaccine epitopes to SARS-CoV-2: “((B-cell) OR (B cell)) AND (
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    All predicted epitopes able to be searched and defined with SnapGene’s “Find Protein Sequence” feature were included.
    SnapGene’s
    suggested: None

    Results from OddPub: Thank you for sharing your code and 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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04360551RecruitingPilot Clinical Trial of the Safety and Efficacy of Telmisart…


    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.

    Results from scite Reference Check: We found no unreliable references.


    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.