Preliminary nonclinical safety and immunogenicity of an rVSV-ΔG-SARS-CoV-2-S vaccine in mice, hamsters, rabbits and pigs

  1. Noa Madar-Balakirski
  2. Amir Rosner
  3. Sharon Melamed
  4. Boaz Politi
  5. Michal Steiner
  6. Hadas Tamir
  7. Yfat Yahalom-Ronen
  8. Elad Bar-David
  9. Amir Ben-Shmuel
  10. Assa Sittner
  11. Itai Glinert
  12. Shay Weiss
  13. Erez Bar-Haim
  14. Hila Cohen
  15. Uri Elia
  16. Hagit Achdout
  17. Noam Erez
  18. Shahar Rotem
  19. Shlomi Lazar
  20. Abraham Nyska
  21. Shmuel Yitzhaki
  22. Adi Beth-Din
  23. Haim Levy
  24. Nir Paran
  25. Tomer Israely
  26. Hadar Marcus

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Abstract

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  1. Version published to 10.1007/s00204-021-03214-w
  2. ScreenIT

    SciScore for 10.1101/2021.07.06.451119: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: 2.3 Ethics statement: Experiments were approved by the IIBR animal care and use committee (IACUC) and performed in accordance with the guidelines of the care and use of laboratory animals published by the Israeli Ministry of Health
    Euthanasia Agents: 2.9 Vaccine Replication in the K18 hACE2 transgenic mouse model: Animals were euthanized by cervical dislocation immediately following vaccination (time 0), 24, 48 and 72 hours post vaccination (n=4 mice per time point).
    Sex as a biological variableFemale New Zealand White (NZW) rabbits were obtained from Charles River, France, and were 14-16 weeks of age at study initiation.
    Randomizationnot detected.
    BlindingHistopathologic changes consistent with neurovirulence were scored, in a double blinded manner, based on the presence and severity of perivascular infiltrates, gliosis, neurodegeneration, satellitosis, and necrosis.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Control animals were injected with carrier buffer at an identical dose volume and under identical experimental conditions. 2.5 Immunogenicity and Cellular Immunity Determination: The immunogenicity of the vaccine was evaluated by determining the NT50 values of neutralizing antibodies against SARS-CoV-2 (the dilution at which 50% neutralization was observed), as was assessed by the plaque reduction neutralization test (PRNT) [6].
    SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Primary recovery of the rVSV-ΔG-SARS-CoV-2-S was performed in BHK-21 cells infected with Modified Vaccinia Ankara T7 (MVA-T7), followed by co-transfection with the rVSV-SARS-CoV-2-S, and the VSV accessory plasmids encoding for VSV-N, P, L and G proteins under control of a T7 promoter.
    BHK-21
    suggested: None
    The organs were processed for titration in 1.5ml ice-cold PBS and titered on VERO-E6 cells.
    VERO-E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    2.2 Animals: C57BL/6J, knockout for type I interferon (IFN) receptors (Ifnar−/−) and hACE2-K18 mice were obtained from The Jackson Laboratory, USA, and were 6-12 weeks of age at study initiation.
    C57BL/6J
    suggested: None
    hACE2-K18
    suggested: None
    K18 hACE2 transgenic mice were vaccinated by a single i.m. injection (hind limb) at a dose of 107 PFU and at a dose volume of 0.05 ml/animal.
    K18 hACE2
    suggested: RRID:IMSR_GPT:T037657)
    For histopathology evaluations, rVSV-ΔG-SARS-CoV-2-S C57BL/6 (n=3), rVSV-ΔG-SARS-CoV-2-S IFNAR (n=6) or VSV-WT C57BL/6 (n=5) intracranially injected mice were sacrificed on day 14, 14 and 2, respectively.
    C57BL/6
    suggested: None
    Recombinant DNA
    SentencesResources
    2.1 Virus and vaccine: Generation of the pVSVΔG-S construct was described in detail, previously [6].
    pVSVΔG-S
    suggested: None
    Briefly, the pVSV-spike expression plasmid was constructed by PCR amplification of the full-length human codon-optimized S gene from pCMV3-SARS-CoV-2 S expression plasmid (Sino Biological, Cat# VG40588-UT) that was used to replace the VSV-G (Glycoprotein) open reading frame within the VSV full length expression vector, yielding pVSV-ΔG-spike.
    pVSV-spike
    suggested: None
    pCMV3-SARS-CoV-2 S
    suggested: None
    pVSV-ΔG-spike
    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04608305RecruitingEvaluate the Safety, Immunogenicity and Potential Efficacy o…

    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.

    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.

  3. Version published to 10.1101/2021.07.06.451119v1 on bioRxiv