A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model

  1. Izabela K Ragan
  2. Lindsay M Hartson
  3. Taru S Dutt
  4. Andres Obregon-Henao
  5. Rachel M Maison
  6. Paul Gordy
  7. Amy Fox
  8. Burton R Karger
  9. Shaun T Cross
  10. Marylee L Kapuscinski
  11. Sarah K Cooper
  12. Brendan K Podell
  13. Mark D Stenglein
  14. Richard A Bowen
  15. Marcela Henao-Tamayo
  16. Raymond P Goodrich

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Abstract

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

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  1. Version published to 10.3390/vaccines9040340
  2. ScreenIT

    SciScore for 10.1101/2020.11.13.381335: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Animal testing and research received ethical approval by the Institutional Animal Care and Use Committee (IACUC) (protocol #18-1234A).
    RandomizationNo animals were excluded from the analyses (1 animal death occurred in the non-adjuvanted group [SvX, SC] prior to administration of the 2nd vaccine dose due to factors not related to the vaccine), and all animals were randomized to the different treatment groups.
    BlindingHistopathology analyses were performed blinded to the experimental cohort conditions.
    Power Analysisnot detected.
    Sex as a biological variableA total of 32 male Golden Syrian hamsters (Mesocricetus auratus) at 6 weeks of age were acquired from Charles River Laboratories (Wilmington, MA).
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    ELISA for anti S1, S2 and RBD antibodies: ELISA was performed to evaluate antibody binding to SARS-CoV-2 spike protein region S1 (16-685 amino acids), S2 (686-1213 amino acids), and RBD (319-541 amino acids) (all recombinant proteins from SinoBiological, Wayne, PA).
    anti S1
    suggested: None
    S2
    suggested: None
    686-1213 amino acids) ,
    suggested: None
    After washing, 1:10,000 dilution of HRP conjugated anti-hamster IgG (H+L) secondary antibody (Jackson Immuno Research, 107-035-142) prepared in blocking buffer was added and incubated for 1 hour.
    anti-hamster IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Following incubation, serum-virus mixtures were plated onto Vero E6 plates as described for virus plaque assays.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Reads were mapped to a SARS-CoV-2 reference sequence that corresponded to the consensus sequence of the virus used for vaccine production using bowtie2.
    bowtie2
    suggested: (Bowtie 2, RRID:SCR_016368)
    Quality and quantity of cDNA was determined via Agilent TapeStation analysis using a HS-D5000 screen tape (Fig.
    Agilent TapeStation
    suggested: (Agilent TapeStation Laptop, RRID:SCR_019547)
    Cell Ranger 10× Genomics, v3.0.2) to generate fastq files and aligned to the Mesocricetus auratus (accession GCA_000349665) and SARS-CoV-2 (reference genome MN985325) reference genomes using CellRanger count pipeline.
    Genomics
    suggested: (UTHSCSA Genomics Core, RRID:SCR_012239)
    Filtered barcode matrices were analyzed by Seurat package Version 3.0
    Seurat
    suggested: (SEURAT, RRID:SCR_007322)
    Differentially expressed genes (DEGs) between non-vaccinated group and vaccinated groups were identified using DESeq2 algorithm, with a Bonferroni-adjusted p< 0.05 and a log2 fold change > 1.
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    Analysis was performed using GraphPad Prism software (version 8.4.2)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad Software, Inc, La Joia, CA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    The flow cytometry results were analyzed using FlowJo as well as a newly published methodology [29].
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    Results from OddPub: Thank you for sharing your code.

    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:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • No funding statement was detected.
    • 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.

  3. Version published to 10.1101/2020.11.13.381335v1 on bioRxiv