A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2

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Abstract

No abstract available

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  1. SciScore for 10.1101/2021.04.12.21255368: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written informed consent prior to the study.
    IRB: H7886) Human Research Ethics Committees.
    IACUC: Animal studies and related experimental procedures were approved by the University of Melbourne Animal Ethics Committee (no. 1714193, no. 1914874).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The nitrocellulose membrane strip has three stripes, the first of which is a recombinant chimeric protein consisting of the extracellular domain of human ACE2 fused to human-IgG1-Fc domain line (test line 1), a control/reference line (Ref Line) coated with anti-chicken IgY antibody and a total anti-RBD antibody line (test Line 2) coated with recombinant RBD protein.
    human-IgG1-Fc domain line ( test line 1)
    suggested: None
    anti-RBD
    suggested: None
    Anti-SARS-CoV-2 RBD antibodies, if present in the specimen, will bind to the RBD-biotin-Au conjugates.
    Anti-SARS-CoV-2 RBD
    suggested: None
    If no antibody is present, or if the antibodies bind to RBD protein but without capacity to interfere with ACE2 binding (i.e., lack of neutralization), then the maximum amount of RBD-gold will bind to the ACE2 line (test line 1).
    ACE2
    suggested: None
    In either case, as the sample continues to flow, the chicken IgY-gold will bind to the anti-chicken IgY line (control/reference line), and next, additional SARS-CoV-2 conjugate will flow to test line 2, where binding of antibody-antigen complexes to the same or related antigen on the test strip will indicate the presence of antibodies to SARS-CoV-2 that may or may not be neutralizing because ACE2 is not involved in this interaction.
    anti-chicken IgY
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Residual virus infectivity in the plasma/virus mixtures was assessed in quadruplicate wells of Vero cells incubated in serum-free media containing 1 μg/ml of Tosyl phenylalanyl chloromethyl ketone (TPCK) trypsin at 37C and 5% CO2; viral cytopathic effect was read on day 5.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    The neutralizing antibody titre was calculated using the Reed–Muench method, as previously described35 Statistics: Regression lines fitted in GraphPad Prism 9.0 using a semi-log non-linear fit, plotted with 95% CI bands.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    A rapid (20 minute) test using fingerprick whole blood overcomes limitations associated with current tests, requiring venous blood draw and laboratory equipment with results taking a minimum of three hours. Portable strip-reading instruments such as the Axxin AX-2S used here are commercially available and can be deployed in non-laboratory locations such as airports and aged care or educational facilities, and the use of dedicated readers (and potentially even smartphone Apps) can provide a quantitative assessment of neutralising antibody levels. Even in the absence of a dedicated instrument, a semi-quantitative assessment by eye, visually comparing the intensity of the test line to the reference line, should provide sufficient information on whether an individual has an acceptable level of immunity, using the same principle used to determine CD4 T-cell levels in the semi-quantitative VISITECT® CD4 tests20. An additional risk that threatens to reduce the durability of immune protection is posed by the emergence of mutant strains of SARS-CoV-2, including the B.1.1.7 lineage (also known as the UK variant), the B.1.351 lineage (South Africa variant) and B.1.1.28 lineage (Brazil) that are considered to be variants of concern (VOCs). Each of these VOCs are more infectious, and potentially induce more severe disease. While they carry mutations throughout various viral proteins, the key mutations appear to be those in the RBD region (N501Y in B.1.1.7; N501Y, E484K and K417N in B.1.35...

    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

    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.