Protective efficacy of a SARS-CoV-2 DNA vaccine in wild-type and immunosuppressed Syrian hamsters

  1. Rebecca L. Brocato
  2. Steven A. Kwilas
  3. Robert K. Kim
  4. Xiankun Zeng
  5. Lucia M. Principe
  6. Jeffrey M. Smith
  7. Jay W. Hooper

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccines.

Article activity feed

  1. Version published to 10.1038/s41541-020-00279-z
  2. ScreenIT

    SciScore for 10.1101/2020.11.10.376905: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Ethics: Animal research was conducted under an IACUC approved protocol at USAMRIID (USDA Registration Number 51-F-00211728 & OLAW Assurance Number A3473-01) in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAnimal Vaccinations: Wild type (females only, aged 6-8 weeks) hamsters (Mesocricetus auratus) were anesthetized by inhalation of vaporized isoflurane using an IMPAC6 veterinary anesthesia machine.
    Cell Line AuthenticationContamination: Clarified virus was subjected to the following specifications: Identification by SARS-CoV-2 RT-PCR assay, Quantification by agarose-based plaque assay, free from contaminants by growth of chocolate agar plates, endotoxin testing using Endosafe® nexgen-PTS, and mycoplasma using MycoAlert test kit, and genomic sequencing.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Expression of the spike protein from pWRG/nCoV-S(opt) was confirmed by transfection of 293T cells followed by immunofluoresence antibody test (IFAT) using heat inactivated (56°C 30 min) human convalescent plasma NRS-53265 (ATCC, Manassa, VA) and compared to empty vector (Suppl. Fig. 1).
    293T
    suggested: None
    HEK293T cells were seeded in T75 tissue culture flasks to be ∼80% confluent the following day and were transfected with the plasmid of interest using Fugene 6 (Promega).
    HEK293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Contrast was adjusted equally for all images with Photoshop Lightroom and then exported as PNG files.
    Photoshop
    suggested: (Adobe Photoshop, RRID:SCR_014199)
    Statistical analyses: Statistical analyses were completed using GraphPad Prism 8.
    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.
    • Thank you for including a protocol registration statement.

    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.

  3. Version published to 10.1101/2020.11.10.376905v1 on bioRxiv