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

Background

Current worldwide pandemic coronavirus disease 2019 (COVID-19) with high numbers of mortality rates and huge economic problems require an urgent demand for safe and effective vaccine development. Inactivated SARS-CoV2 vaccine with alum. Hydroxide can play an important role in reducing the impacts of the COVID-19 pandemic. In this study, vaccine efficacy was evaluated through the detection of the neutralizing antibodies that protect mice from challenge with SARS-CoV 2 3 weeks after the second dose. We conclude that the vaccine described here has safety and desirable properties, and our data support further development and plans for clinical trials.

Methods

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 were isolated from Egyptian patients SARS-CoV-2-positive. Development of inactivated vaccine was carried out in a BSL-3 facilities and the immunogenicity was determined in mice at two doses (55 and 100 μg per dose).

Results

The distinct cytopathic effect induced by SARS-COV-2 propagation on Vero cell monolayers and the viral particles were identified as Coronaviridae by transmission electron microscopy and RT-PCR on infected cells cultures. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless of the dose concentration, with excellent safety profiles and no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by the wild virus challenge of the vaccinated mice and viral replication detection in lung tissues.

Conclusions

Vaccinated mice recorded complete protection from challenge infection via inhibition of SARS-COV-2 replication in the lung tissues of mice following virus challenge, regardless of the level of serum neutralizing antibodies. This finding will support future trials for the evaluation of an applicable SARS-CoV-2 vaccine candidate.

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  1. Version published to 10.1093/abt/tbab012
  2. ScreenIT

    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

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  3. Version published to 10.1101/2021.03.01.433130 on bioRxiv