A Single Dose of the Deactivated Rabies-Virus Vectored COVID-19 Vaccine, CORAVAX, Is Highly Efficacious and Alleviates Lung Inflammation in the Hamster Model

  1. Drishya Kurup
  2. Christoph Wirblich
  3. Leila Zabihi Diba
  4. Rachael Lambert
  5. Megan Watson
  6. Noor Shaikh
  7. Holly Ramage
  8. Charalambos Solomides
  9. Matthias J. Schnell

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Abstract

Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS-CoV-2 S1-specific and virus-neutralizing antibodies (VNAs) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual-antigen vaccine candidate for clinical evaluation against SARS-CoV-2 and Rabies virus.

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  1. Version published to 10.3390/v14061126
  2. ScreenIT

    SciScore for 10.1101/2022.02.21.481324: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Thomas Jefferson University (TJU) is an AAALAC-accredited institution, and the IACUC Committee approved all animal work of TJU.
    IACUC: Thomas Jefferson University (TJU) is an AAALAC-accredited institution, and the IACUC Committee approved all animal work of TJU.
    Euthanasia Agents: Five of the animals in each group were euthanized by an overdose of CO2 inhalation on day 3 (day 42), day 7 (day 46), and day 14(53) p.c.
    Sex as a biological variableSix to eight-week-old golden Syrian female hamsters (Envigo) were anesthetized with 5% isoflurane before immunization, blood collection, and the SARS-CoV-2 challenge.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Enzyme-linked immunosorbent assay: To determine antibody responses to the S protein of SARS-CoV-2, an indirect ELISA was developed utilizing purified S1 or receptor-binding domain (RBD) protein.
    receptor-binding domain (RBD) protein.
    suggested: None
    Plates were washed three times the next day, followed by the addition of 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) or mouse anti-hamster-IgG1-HRP (Southern Biotech, Cat# 1940–05, 1:8000 in PBST) for 2 h at RT.
    anti-Syrian hamster IgG
    suggested: (Jackson ImmunoResearch Labs Cat# 107-035-142, RRID:AB_2337454)
    anti-hamster-IgG2/3-HRP
    suggested: None
    anti-hamster-IgG1-HRP
    suggested: None
    SARS CoV-2 neutralizing antibody response: Sera collected from animals were tested for neutralizing capabilities against SARS-CoV-2.
    SARS-CoV-2
    suggested: None
    The primary antibody, human Anti-SARS COV-2 Nucleocapsid monoclonal (E16C) (Thermo Fisher, MA1-7403, 0.1 mg/mL), was incubated as a 1:100 dilution, at room temperature, for 45 minutes.
    The primary antibody, human Anti-SARS COV-2 Nucleocapsid monoclonal (E16C)
    suggested: None
    Anti-SARS COV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus stocks were obtained at passage 4 (GenBank: MN985325.1) and propagated in Vero E6 cells.
    Vero E6
    suggested: RRID:CVCL_XD71)
    The stock used in this study is passage 5. Cells: Vero (ATCC, CCL81), Vero E6 (ATCC, CRL-1586), BSR (a clone of Baby hamster kidney cells), HEK-293T (ATCC, CRL 3216), Effector cells (murine FcγRIV ADCC Bioassay Effector Cells, Promega-M1201) Vaccine production and purification: Recombinant RABV were recovered, purified, inactivated, and tittered as described previously11.
    Vero
    suggested: ATCC Cat# CCL-81, RRID:CVCL_0059)
    HEK-293T
    suggested: None
    Recombinant proteins for ELISA: Purification of the HA-tagged S1 protein from the supernatant of transfected cells for ELISA: Sub-confluent T175 flasks of 293T cells (human embryonic kidney cell line, ATCC) were transfected with a pDisplay vector encoding amino acids 16 to 682 of SARS-CoV-2 S (S1) fused to a C-terminal hemagglutinin (HA) peptide using X-tremeGENE 9 reagent (Millipore Sigma, Cat# 6365809001).
    293T
    suggested: None
    Antibody-dependent effector functions: The assay was performed in 96-well, flat, white-bottom plates (Corning) preseeded with 30,000 Vero CCL81 cells and infected after 24 h with Measles vaccine (Edmonston B) vector expressing full-length SARS CoV-2 spike at an MOI of 0.5.
    Vero CCL81
    suggested: None
    Genetically modified Jurkat cells expressing mouse FcγR IV with a luciferase reporter gene under the transcriptional control of nuclear-factor-activated T cell (NFAT) promoter were added at 1.5 × 105 cells in 25 μl per well, which is approximately a 5:1 ratio of effector cells (Promega) to target cells.
    Jurkat
    suggested: None
    Recombinant DNA
    SentencesResources
    Recombinant proteins for ELISA: Purification of the HA-tagged S1 protein from the supernatant of transfected cells for ELISA: Sub-confluent T175 flasks of 293T cells (human embryonic kidney cell line, ATCC) were transfected with a pDisplay vector encoding amino acids 16 to 682 of SARS-CoV-2 S (S1) fused to a C-terminal hemagglutinin (HA) peptide using X-tremeGENE 9 reagent (Millipore Sigma, Cat# 6365809001).
    pDisplay
    suggested: RRID:Addgene_51053)
    Software and Algorithms
    SentencesResources
    Data were analyzed with GraphPad Prism (Version 8.0 g) using 4-parameter nonlinear regression to determine the titer at which the curves reach 50% of the top plateau value (50% effective concentration [EC50]).
    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.
    • 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 10.1101/2022.02.21.481324 on bioRxiv