Safety and Immunogenicity Evaluation of Inactivated whole-virus-SARS-COV-2 As Emerging Vaccine Development In Egypt

  1. Amani A. Saleh
  2. Mohamed A. Saad
  3. Islam Ryan
  4. Magdy Amin
  5. Mohamed I. Shindy
  6. Wael A. Hassan
  7. Mahmoud Samir
  8. Ayman A. Khattab
  9. Sherein S. Abdelgayed
  10. Mohamed G. Seadawy
  11. Hossam M. Fahmy
  12. Khaled Amer

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Abstract

The current worldwide pandemic COVID-19 is causing severe human health problems, with high numbers of mortality rates and huge economic burdens that require an urgent demand for safe, and effective and vaccine development. Our study was the first trail to development and evaluation of safety and immune response to inactivated whole SARS-COV-2 virus vaccine adjuvanted with aluminium hydroxide. We used characterized SARS-COV-2 strain, severe acute respiratory syndrome coronavirus 2 isolates (SARS-CoV-2/human/EGY/Egy-SERVAC/2020) with accession numbers; MT981440 ; MT981439; MT981441; MT974071; MT974069 and MW250352 at GenBank that isolated from Egyptian patients SARS-CoV-2-positive. Development of the vaccine was carried out in a BSL - 3 facilities and the immunogenicity was determined in mice at two doses (55µg and 100µg per dose). All vaccinated mice were received a booster dose 14 days post first immunization. Our results demonstrated distinct cytopathic effect on the vero cell monolayers induced through SARS-COV-2 propagation and the viral particles were identified as Coronaviridae by transmission electron microscopy. SARS-CoV-2 was identified by RT-PCR performed on the cell culture. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless the dose concentration, with excellent safety profiles.However, no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by wild virus challenge the vaccinated mice and detection of viral replication in lung tissues. Vaccinated mice recorded complete protection from challenge infection three weeks post second dose. SARS-COV-2 replication was not observed in the lungs of mice following SARS-CoV-2 challenge, regardless of the level of serum neutralizing antibodies. This finding will support the future trials for evaluation an applicable SARS-CoV-2 vaccine candidate.

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    SciScore for 10.1101/2021.03.01.433130: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The approval of the ethics institutional review board (IRB) of Ministry of Defense, written informed consent was obtained from the participants.
    Consent: The approval of the ethics institutional review board (IRB) of Ministry of Defense, written informed consent was obtained from the participants.
    Randomizationnot detected.
    BlindingThree blind passages [12] followed by seven successive serial passages were obtained and tissue culture suspensions were collected for virus detection and quantification by Real-time PCR.
    Power Analysisnot detected.
    Sex as a biological variableSafety has been documented in repeat-dose toxicity studies in mice (female, 6-8weeks old) which were vaccinated intraperitoneally (i.p) with three doses (N+1) at 55 and 110 µg/dose of inactivated vaccine candidate without adjuvant on day 0, 7 and 14 [18].
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The isolated SARS-CoV2 that has been propagated five times on serum protein free Vero SF cells was used for homologous challenge.
    Vero SF
    suggested: None
    Tissue samples were thawed and homogenised in 1ml of Vero cell culture medium supplemented with antibiotics for titration in the TCID50 assay [21].
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    Extracted RNA concentration and purity were tested with NanoDrop spectrophotometer (Thermo Fisher Scientific, USA).
    NanoDrop
    suggested: None
    Purified libraries were qualified and quantified by Agilent Bioanalyzer and Qubit 4 Flurometer (Thermo Scientific, USA).
    Agilent Bioanalyzer
    suggested: None
    Virus sequence assembly was performed using The Ion Torrent package (v.5.12) followed by genome mapping using tmap program (v.512) against complete SRAS-CoV-2 genome sequences retrieved from the GISAID website.
    tmap
    suggested: (TMAP, RRID:SCR_000687)

    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.

    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 10.1101/2021.03.01.433130 on bioRxiv