Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques

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Abstract

SARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution, and improved coverage may offer significant public health benefits, especially in resource-limited settings.

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  1. SciScore for 10.1101/2021.09.13.460191: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Animal studies were conducted in compliance with all relevant local, state, and federal regulations and were approved by the Bioqual Institutional Animal Care and Use Committee (IACUC).
    IACUC: Animal studies were conducted in compliance with all relevant local, state, and federal regulations and were approved by the Bioqual Institutional Animal Care and Use Committee (IACUC).
    Sex as a biological variableAnimals, virus stocks, and study design: 21 outbred Indian-origin adult male and female rhesus macaques (Macaca mulatta) ages 6-14 years old were randomly allocated to groups.
    RandomizationAnimals, virus stocks, and study design: 21 outbred Indian-origin adult male and female rhesus macaques (Macaca mulatta) ages 6-14 years old were randomly allocated to groups.
    BlindingAll immunologic and virologic studies were performed blinded.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    ELISPOT plates were coated with mouse anti-human IFN-γ monoclonal antibody from BD Pharmigen at 5 µg/well and incubated overnight at 4°C.
    anti-human IFN-γ
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The WA1/2020 (USA-WA1/2020; BEI Resources; NR-5228) challenge stock was grown in VeroE6 cells and deep sequenced as described previously (33).
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Briefly, the packaging plasmid psPAX2 (AIDS Resource and Reagent Program), luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene), and spike protein expressing pcDNA3.1-SARS CoV-2 SΔCT of variants were co-transfected into HEK293T cells by lipofectamine 2000 (ThermoFisher).
    HEK293T
    suggested: None
    The mixture was incubated at 37°C for 1 h before adding to HEK293T-hACE2 cells.
    HEK293T-hACE2
    suggested: RRID:CVCL_A7UK)
    Recombinant DNA
    SentencesResources
    Briefly, the packaging plasmid psPAX2 (AIDS Resource and Reagent Program), luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene), and spike protein expressing pcDNA3.1-SARS CoV-2 SΔCT of variants were co-transfected into HEK293T cells by lipofectamine 2000 (ThermoFisher).
    psPAX2
    suggested: RRID:Addgene_12260)
    pLenti-CMV
    suggested: None
    pcDNA3.1-SARS
    suggested: None
    The gene fragment was subsequently cloned into a pcDNA3.1+ expression plasmid using restriction site cloning (Integrated DNA Technologies).
    pcDNA3.1+
    suggested: RRID:Addgene_117272)
    Software and Algorithms
    SentencesResources
    Statistical analyses: Comparisons of virologic and immunologic data was performed using GraphPad Prism 8.4.2 (GraphPad Software).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    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: 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:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • 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.