A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19

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Abstract

The development of effective countermeasures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal models of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.

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  1. SciScore for 10.1101/2021.01.29.428442: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: UTMB is an AAALAC-accredited institution and all animal work was approved by the IACUC Committee of UTMB.
    Randomizationnot detected.
    BlindingThe blinded tissue sections were semi-quantitatively scored for pathological lesions using the criteria described in Supplemental Table 1.
    Power Analysisnot detected.
    Sex as a biological variablePathogenicity of SARS-CoV-2 in hamsters: On day 0, seven week-old golden Syrian female hamsters (Envigo) were anesthetized with ketamine/xylazine, and 8 animals were exposed intransally to the targeted dose of 105 PFU of SARS-CoV-2 in a volume of 100 μl, while 4 animals were mock-infected with 100 μl 1X DPBS.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibodies: Monoclonal antibody CR3022 was produced by transient transfection of 293F cells with cDNA expression plasmids obtained from BEI resources.
    Antibodies
    suggested: (Imported from the IEDB Cat# CR3022, RRID:AB_2848080)
    Monoclonal antibodies I1 and I14 against the VSV glycoprotein and monoclonal antibody 23H12 against the VSV matrix protein were purified from hybridoma supernatant by affinity chromatography on Protein G sepharose.
    I14 against the VSV glycoprotein
    suggested: None
    The proteins were transferred to nitrocellulose membrane and probed with polyclonal rabbit serum against SARS-CoV S1 domain (Thermofisher, Cat No. PA5-81798 and PA5-81795), monoclonal antibodies I1 (8G5F11) and I14 (IE9F) against the VSV glycoprotein and monoclonal antibody 23H12 against VSV matrix protein provided by Douglas Lyles (Wake Forest University).
    VSV glycoprotein
    suggested: None
    After washing with DPBS the cells were incubated for 2 hours with monoclonal antibody CR3022 conjugated to Dylight 550 or a mixture of monoclonal antibodies I1 and I14 conjugated to Dylight 488.
    I14
    suggested: (Rockland Cat# 200-401-I14, RRID:AB_2612206)
    Antibody responses to SARS-CoV-2 spike protein (S1) were measured by an indirect ELISA as described previously(Kurup et al., 2015).
    SARS-CoV-2 spike protein ( S1
    suggested: None
    The secondary antibodies used in the ELISA are HRP-conjugated goat anti-syrian hamster IgG secondary antibody (Jackson immunoresearch, Cat# 107-035-142, 1:8000 in PBST) or mouse anti-hamster-IgG2/3-HRP (Southern Biotech, Cat# 1935-05, 1:8000 in PBST).
    anti-syrian hamster IgG
    suggested: (Jackson ImmunoResearch Labs Cat# 107-035-142, RRID:AB_2337454)
    anti-hamster-IgG2/3-HRP
    suggested: None
    Neutralizing antibody response: Sera collected from animals were tested for neutralizing capabilities against SARS-CoV-2.
    SARS-CoV-2
    suggested: None
    As the secondary antibody, HRP-labeled goat anti-human IgG (SeraCare) was used at dilution 1:500.
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The recombinant virus was recovered on 293T cells as described previously, filtered through an 0.22 μm filter and used to inoculate Vero (CCL-81, ATCC) or human BEAS-2B lung cells (gift from R. Plemper, University of Georgia).
    293T
    suggested: None
    BEAS-2B
    suggested: BCRJ Cat# 0395, RRID:CVCL_0168)
    For immunofluorescence staining, Vero E6 cells were seeded on coverslips and infected at three different MOI ranging from 0.01 to 0.1 PFU.
    Vero E6
    suggested: RRID:CVCL_XD71)
    To assess viral replication of ConVac in vitro, Vero (CCL-81) cells were seeded in 6-well plates and infected next day at 34°C at an MOI of 5 and 0.05 PFU.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    UTMB is an AAALAC-accredited institution and all animal work was approved by the IACUC Committee of UTMB.
    UTMB
    suggested: None
    Data were analyzed with GraphPad Prism (Version 8.4.3) using 4-parameter nonlinear regression.
    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: 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

    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.