Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

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  1. SciScore for 10.1101/2021.01.19.427373: (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.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableVaccination and SARS-CoV-2 challenge: Seven-week-old golden Syrian female hamsters (Envigo) were anesthetized with 5% isoflurane prior to immunization and blood collections and with ketamine/xylazine prior to the SARS-CoV-2 challenge.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Virus stocks were propagated in Vero E6 cells and a passage 4 was used.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Briefly, X-tremeGENE 9 transfection reagent (Millipore Sigma, Cat# 6365809001) was used to cotransfect the full-length viral cDNA clone encoding CORAVAX along with the plasmids encoding RABV N, P, and L proteins and the T7 RNA polymerase into BEAS-2B human lung cells in 6-well plates (RABV).
    BEAS-2B
    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

    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.