A Newcastle Disease Virus (NDV) Expressing a Membrane-Anchored Spike as a Cost-Effective Inactivated SARS-CoV-2 Vaccine

  1. Weina Sun
  2. Stephen McCroskery
  3. Wen-Chun Liu
  4. Sarah R. Leist
  5. Yonghong Liu
  6. Randy A. Albrecht
  7. Stefan Slamanig
  8. Justine Oliva
  9. Fatima Amanat
  10. Alexandra Schäfer
  11. Kenneth H. Dinnon
  12. Bruce L. Innis
  13. Adolfo García-Sastre
  14. Florian Krammer
  15. Ralph S. Baric
  16. Peter Palese

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Abstract

A successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine must not only be safe and protective, but must also meet the demand on a global scale at a low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent coronavirus disease 2019 (COVID-19) vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.30.229120: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Recombinant DNA experiments were performed in accordance with protocols approved by the Icahn School of Medicine at Mount Sinai Institutional Biosafety Committee (IBC)
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableImmunization and challenge study in BALB/c mice: Seven-week old female BALB/cJ mice (Jackson Laboratories) were used in this study.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The membrane was washed with PBST on a shaker three times (10 min at RT each time) and incubated with an S-specific mouse monoclonal antibody 2B3E5 (provided by Dr. Thomas Moran at ISMMS) or an HN-specific mouse monoclonal antibody 8H2 (MCA2822, Biorad) diluted in PBST containing 1% bovine serum albumin (BSA), overnight at 4°C.
    MCA2822
    suggested: None
    ELISA plates were washed 3 times with PBST and incubated in 50 μL per well of sheep anti-mouse IgG-horseradish peroxidase (HRP) conjugated antibody (GE Healthcare) or goat anti-hamster IgG-HRP conjugated antibody (Invitrogen) diluted (1:3,000) in blocking solution.
    anti-mouse IgG-horseradish
    suggested: None
    anti-hamster IgG-HRP
    suggested: None
    Cells were then stained with 100 μL per well of a mouse monoclonal anti-NP antibody (1C7), kindly provided by Dr. Thomas Moran at ISMMS, at 1μg/ml for 1h at RT.
    anti-NP
    suggested: None
    Cells were washed with PBS and incubated with 100 μL per well antimouse IgG HRP (Rockland) secondary antibody at 1:3,000 dilution in PBS containing 1% dry milk for 1h at RT.
    antimouse IgG
    suggested: (Roche Cat# 760-500, RRID:AB_2753116)
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 isolate USA-WA1/2020 (WA-1, BEI Resources NR-52281) used for hamster challenge were propagated in Vero E6 cells (ATCC CRL-1586) in Dulbecco’s Modified Eagle Medium (DMEM), supplemented with 2% fetal bovine serum (FBS), 4.5 g/L D-glucose, 4 mM L-glutamine, 10 mM
    Vero E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Immunization and challenge study in BALB/c mice: Seven-week old female BALB/cJ mice (Jackson Laboratories) were used in this study.
    BALB/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    BALB/cJ
    suggested: RRID:IMSR_JAX:000651)
    Software and Algorithms
    SentencesResources
    The sequences of the transgenes were confirmed by Sanger Sequencing (Genewiz)
    Genewiz
    suggested: (GENEWIZ, RRID:SCR_003177)
    Non-linear regression curve fit analysis (The top and bottom constraints were set at 100% and 0%) over the dilution curve was performed to calculate 50% of inhibitory dilution (ID50) of the serum using GraphPad Prism 7.0.
    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

  2. Version published to 10.3390/vaccines8040771
  3. Version published to 10.1101/2020.07.30.229120v1 on bioRxiv