Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection

  1. Anne C. Moore
  2. Emery G. Dora
  3. Nadine Peinovich
  4. Kiersten P. Tucker
  5. Karen Lin
  6. Mario Cortese
  7. Sean N. Tucker

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Abstract

There is an urgent need to develop efficacious vaccines against SARS-CoV-2 that also address the issues of deployment, equitable access, and vaccine acceptance. Ideally, the vaccine would prevent virus infection and transmission as well as preventing COVID-19 disease. We previously developed an oral adenovirus-based vaccine technology that induces both mucosal and systemic immunity in humans. Here we investigate the immunogenicity of a range of candidate adenovirusbased vaccines, expressing full or partial sequences of the spike and nucleocapsid proteins, in mice. We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Antigen-specific CD4+ and CD8+ T cells were induced by this leading vaccine candidate at low and high doses. This fulllength spike antigen plus nucleocapsid adenovirus construct has been prioritized for further clinical development.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.04.283853: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Animal Experiments: Studies were approved for ethics by the Animal Care and Use Committees (IACUC).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableFemale 6-8 week old Balb/c mice were purchased from Jackson labs (Bar Harbor, ME).

    Table 2: Resources

    Antibodies
    SentencesResources
    This ELISA-based kit detects antibodies that hinder the interaction between the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein and the ACE2 receptor on host cells, and is highly correlated to conventional virus neutralizing titers for SARS-CoV-2 infection of Vero cells53.
    SARS-CoV-2 spike glycoprotein
    suggested: None
    The absorbance of a given sample is inversely related on the titer of anti-SARS-CoV-2 RBD neutralizing antibody in a given sample.
    anti-SARS-CoV-2 RBD
    suggested: None
    The antibodies used were APC-H7 conjugated CD4, FITC conjugated CD8, BV650 conjugated CD3, PerCP-Cy5.5 conjugated IFN-y, BV421 conjugated IL-2, PE-Cy7 conjugated TNFa, APC conjugated IL-4, Alexa Fluor conjugated CD44, and PE conjugated CD62L (BD biosciences).
    CD8
    suggested: (RayBiotech Cat# CS-11-0250, RRID:AB_1228199)
    BV421
    suggested: None
    CD44
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Female 6-8 week old Balb/c mice were purchased from Jackson labs (Bar Harbor, ME).
    Balb/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    Software and Algorithms
    SentencesResources
    Flow cytometric analysis was performed using an Attune Flow cytometer and Flow Jo version 10.7.1, after staining with the appropriate antibodies.
    Flow Jo
    suggested: (FlowJo, RRID:SCR_008520)

    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.
    • No funding statement was detected.
    • 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.

  2. Version published to 10.1101/2020.09.04.283853v1 on bioRxiv