Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets

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Abstract

The ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These “variants-of-concern” have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively. To address concerns about emerging SARS-CoV-2 variants affecting vaccine-induced immunity, we investigated the neutralisation of representative ‘G614’, ‘501Y.V1’ and ‘501Y.V2’ virus isolates using sera from ferrets that had received prime-boost doses of the DNA vaccine, INO-4800. Neutralisation titres against G614 and 501Y.V1 were comparable, but titres against the 501Y.V2 variant were approximately 4-fold lower, similar to results reported with other nucleic acid vaccines and supported by in silico biomolecular modelling. The results confirm that the vaccine-induced neutralising antibodies generated by INO-4800 remain effective against current variants-of-concern, albeit with lower neutralisation titres against 501Y.V2 similar to other leading nucleic acid-based vaccines.

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  1. SciScore for 10.1101/2021.04.17.440246: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Serum samples: Serum samples used for neutralisation assays were generated and selected with the consent of the sponsor (Coalition for Epidemic Preparedness Innovations), as previously described8.
    IACUC: Parent vaccine efficacy studies were approved by the Animal Ethics Committee at CSIRO ACDP (Approval Reference: AEC 2004).
    Sex as a biological variableIn brief, four male and four female ferrets received two doses of INO-4800 via intramuscular administration of 1 mg plasmid DNA to the caudal thigh muscle, followed by electroporation split across two sites using the CELLECTRA® device.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    VIC31 Passage 2, VIC17990 Passage 2, and 501Y.V2.HV001 Passage 4 virus stocks were grown in VeroE6 cells (CCL81; American Type Culture Collection (ATCC), Manassas, VA, USA).
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    ATCC VeroE6 cells were additionally used for virus neutralisation assays (see below). Next-Generation Sequencing: Virus stocks were sequenced using a MiniSeq platform (Illumina, Inc; San Diego, CA, USA).
    MiniSeq
    suggested: None

    Results from OddPub: Thank you for sharing your 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: 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.
    • 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.

    About SciScore

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