Development of a vaccine against the newly emerging COVID-19 virus based on the receptor binding domain displayed on virus-like particles

  1. Lisha Zha
  2. Hongxin Zhao
  3. Mona O. Mohsen
  4. Liang Hong
  5. Yuhang Zhou
  6. Zehua Li
  7. Hongquan Chen
  8. Xuelan Liu
  9. Xinyue Chang
  10. Jie Zhang
  11. Dong Li
  12. Ke Wu
  13. Monique Vogel
  14. Martin F Bachmann
  15. Junfeng Wang

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Abstract

The ongoing coronavirus COVID-19 pandemic is caused by a new coronavirus (SARS-CoV-2) with its origin in the city of Wuhan in China. From there it has been rapidly spreading to many cities inside and outside China. Nowadays more than 33 millions with deaths surpassing 1 million have been recorded worldwide thus representing a major health issue. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here we demonstrated that recombinantly expressed receptor binding domain (RBD) of the spike protein homologous to SARS binds to ACE2, the viral receptor. Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMV TT ) resulted in a vaccine candidate that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized COVID-19 virus in vitro .

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  1. Version published to 10.1101/2020.05.06.079830v3 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.05.06.079830: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The construct (RBD-huFc) was transformed into bacterial DH5α competent cells, and the extracted plasmid was then transfected into HEK293F cells at a density of 3×106 cells/ml using PEI (Invitrogen, Thermo Fisher Scientific, MA, USA).
    HEK293F
    suggested: None
    Plasmids of pwpxl-luc, HIV-1 PSD and pCMV3 containing the SARS-CoV-2/COVID-19 Spike gene were co-transfected into 7 x 105 293F cells using Sinofection (Sino Biological, Beijing, China).
    293F
    suggested: RRID:CVCL_D615)
    Titration of pseudovirus: The 293T-ACE2 cells which stably express ACE2 receptors on the cell membrane were prepared by transfection of ACE2 gene into 293T cells using lentivirus system.
    293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    After incubation at 37°C for 1 h, the mixture was inoculated on the 293T-ACE2 cells (3 x 104 cells/well).
    293T-ACE2
    suggested: RRID:CVCL_YZ65)
    Experimental Models: Organisms/Strains
    SentencesResources
    Six-week-old naive BALB/c mice (3 mice per group) were immunized by subcutaneous injection with 50 μg of either RBD-CuMVTT, RBD or CuMVTT as control.
    BALB/c
    suggested: None
    Software and Algorithms
    SentencesResources
    Unreacted SMPH and RBD proteins were removed using Amicon-Ultra 0.5, 100K (Merck-Millipore, Burlington, Ma).
    Amicon-Ultra
    suggested: None

    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: 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.

  3. Version published to 10.1101/2020.05.06.079830v2 on bioRxiv
  4. Version published to 10.1101/2020.05.06.079830v1 on bioRxiv