Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2

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Abstract

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  1. SciScore for 10.1101/2020.08.11.247395: (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

    Antibodies
    SentencesResources
    ( C–D) Post-prime (week 2) (C) and post-boost (week 5) (D) anti-S binding titers in Kymab Darwin mice, which are transgenic for the non-rearranged human antibody variable and constant region germline repertoire, measured by ELISA and plotted as in (A).
    Post-prime (week 2
    suggested: None
    anti-S
    suggested: None

    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 Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap used on page 39. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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.

  2. SciScore for 10.1101/2020.08.11.247395: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: After a 7-day acclimation time, mice were anesthetized with a mixture of ketamine/xylazine and challenged intranasally with 105 plaque-forming units (pfu) of mouse-adapted SARS-CoV-2 MA strain for the evaluation of vaccine efficacy (IACUC protocol 20-114.0).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableMouse immunizations and challenge: Female BALB/c (Stock: 000651) mice were purchased at the age of four weeks from The Jackson Laboratory, Bar Harbor, Maine, and maintained at the Comparative Medicine Facility at the University of Washington, Seattle, WA, accredited by the American Association for the Accreditation of Laboratory Animal Care International (AAALAC).
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Plates were washed 4x in TBST, then anti-mouse (Invitrogen) or anti-human (Invitrogen) horseradish peroxidase-conjugated antibodies were diluted 1:5,000 and 25 μL added to each well and incubated at 37°C for 1 h.
    anti-mouse
    suggested: None
    anti-human
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, HEK293T cells were co-transfected using Lipofectamine 2000 (Life Technologies) with an S-encoding plasmid, an MLV Gag-Pol packaging construct, and the MLV transfer vector encoding a luciferase reporter according to the manufacturer’s instructions.
    HEK293T
    suggested: None
    The seed virus was amplified twice in Vero E6 cells at low moi for 48 h to create a working stock which was titered by plaque assay (Hou et al., 2020).
    Vero E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Mouse immunizations and challenge: Female BALB/c (Stock: 000651) mice were purchased at the age of four weeks from The Jackson Laboratory, Bar Harbor, Maine, and maintained at the Comparative Medicine Facility at the University of Washington, Seattle, WA, accredited by the American Association for the Accreditation of Laboratory Animal Care International (AAALAC).
    BALB/c
    suggested: RRID:IMSR_JAX:000651)
    Software and Algorithms
    SentencesResources
    Chromatographic peaks for the most abundant and non-overlapped isotopic peaks were determined and integrated with MassLynx (Waters).
    MassLynx
    suggested: (MassLynx , RRID:SCR_014271)
    Plates were immediately read at 450 nm on a VarioSkanLux plate reader (ThermoFisher) and data plotted and fit in Prism (GraphPad) using nonlinear regression sigmoidal, 4PL, X is log(concentration) to determine EC50 values from curve fits.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Fifty percent inhibition titer (IC50) was calculated in GraphPad Prism 8.3.0 by fitting the data points using a sigmoidal dose-response (variable slope) curve.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Cells were run on the Cytek Aurora and analyzed using FlowJo software (Treestar)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    The data were baseline subtracted and aligned to pre-loading with polyclonal Fabs using the Pall Forté Bio/Sartorius analysis software (version 12.0) and plotted in PRISM.
    PRISM
    suggested: (PRISM, RRID:SCR_005375)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT03547245Active, not recruitingA Phase I Trial to Evaluate the Safety and Immunogenicity of…
    NCT03186781CompletedInfluenza HA Ferritin Vaccine, Alone or in Prime-Boost Regim…
    NCT03814720Active, not recruitingDose, Safety, Tolerability and Immunogenicity of an Influenz…


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 39. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.


    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.