Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates

  1. Gozde Sir Karakus
  2. Cihan Tastan
  3. Derya Dilek Kancagi
  4. Bulut Yurtsever
  5. Gamze Tumentemur
  6. Sevda Demir
  7. Raife Dilek Turan
  8. Selen Abanuz
  9. Didem Cakirsoy
  10. Utku Seyis
  11. Samed Ozer
  12. Omer Elibol
  13. Muhammer Elek
  14. Gurcan Ertop
  15. Serap Arbak
  16. Merve Acikel Elmas
  17. Cansu Hemsinlioglu
  18. Ayse Sesin Kocagoz
  19. Ozden Hatirnaz Ng
  20. Sezer Akyoney
  21. Ilayda Sahin
  22. Ugur Ozbek
  23. Dilek Telci
  24. Fikrettin Sahin
  25. Koray Yalcin
  26. Siret Ratip
  27. Ercument Ovali

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Abstract

COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1 (V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2+ mice.

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  1. Version published to 10.1101/2020.09.04.277426v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.09.04.277426: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Informed consent for participation in this study was obtained from participants.
    IRB: The study for SARS-CoV-2 genome sequencing was approved by the Ethics Committee of Acıbadem Mehmet Ali Aydınlar University (ATADEK-2020/05/41) and informed consent from the patients was obtained to publish identifying information/images.
    IACUC: All animal studies received ethical approval by the Yeditepe University Animal Experiments Local Ethics Committee (Yeditepe-HADYEK).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableFemale or male 11-months-old BALB/c mice were housed in AAALAC International accredited Acıbadem Mehmet Ali Aydinlar University Laboratory Animal Application and Research Center (ACUDEHAM; Istanbul, Turkey) for 7-day toxicity and 21-day toxicity and efficacy tests.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    To detect the SARS-COV-2 IgG antibody in mouse serum SARS-COV-2 IgG ELISA Kit (Creative, DEIASL019) was used.
    SARS-COV-2 IgG
    suggested: None
    500,000 cells in 100 μl were added into microplate already coated with a monoclonal antibody specific for mouse IFN-γ.
    IFN-γ
    suggested: None
    Also, in order to determine T cell activation and proliferation, the restimulated cells were stained with the antibodies including CD3, CD4, CD8, CD19, and CD25 as an activation marker (Miltenyi Biotec).
    CD3
    suggested: (Miltenyi Biotec Cat# 130-094-531, RRID:AB_2721154)
    CD4
    suggested: (Miltenyi Biotec Cat# 130-095-243, RRID:AB_10827681)
    CD8
    suggested: None
    CD19
    suggested: None
    CD25
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The neutralization ratio was determined by assessing percent neutralization by dividing the index value of serum-virus treated condition wells by the cell index value of untreated control Vero cells (normalized to 100%).
    Vero
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    For 34-day efficacy tests, female or male 3-months-old BALB/c mice were housed in Yeditepe University Experimental Research Center.
    BALB/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    Software and Algorithms
    SentencesResources
    LC-MSMS data was searched against the NCBI RefSeq sequence database for protein identification.
    RefSeq
    suggested: (RefSeq, RRID:SCR_003496)
    Statistical analyses were performed using SPSS Statistics software.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 34. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  3. Version published to 10.1101/2020.09.04.277426v1 on bioRxiv