A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities

  1. Di Yin
  2. Sikai Ling
  3. Xiaolong Tian
  4. Yang Li
  5. Zhijue Xu
  6. Hewei Jiang
  7. Xue Zhang
  8. Xiaoyuan Wang
  9. Yi Shi
  10. Yan Zhang
  11. Lintai Da
  12. Sheng-ce Tao
  13. Quanjun Wang
  14. Jianjiang Xu
  15. Tianlei Ying
  16. Jiaxu Hong
  17. Yujia Cai

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.05.14.093054: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The animal study has complied with the guidelines of the Institutional Animal Care and Use Committee (IACUC) of the Shanghai Jiao Tong University.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableMice: 6-8 weeks old, male, specific-pathogen-free (SPF) C57BL/6 mice were inoculated with VSP, IDLV, or PBS by foot-pad injection.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The membrane was blocked by 5% fat-free milk dissolved in TBS/0.05% Tween-20 for 1 hr then cut off according to the marker and incubated with anti-flag monoclonal antibody (Sigma) overnight at 4°C.
    anti-flag
    suggested: None
    The membranes were incubated with anti-mouse secondary antibodies (Cell Signaling Technology) for 1 hr at room temperature.
    anti-mouse secondary antibodies ( Cell Signaling Technology ) for 1
    suggested: None
    Cells were then stained by anti-flag tag antibody (Proteintech) followed by Alexa Fluor 555 IgG incubation (Cell Signaling Technology) and nuclei staining with DAPI (Beyotime Biotechnology).
    anti-flag tag
    suggested: (Cell Signaling Technology Cat# 3768, RRID:AB_1642183)
    Experimental Models: Cell Lines
    SentencesResources
    Cell cultures: 293T and Huh-7 cells were cultured in DMEM (Gibco, USA) supplemented with 10% fetal bovine serum (Gibco, USA) and 1% penicillin/streptomycin (P/S) (Thermo Fisher Scientific,
    293T
    suggested: None
    THP-1 cells were differentiated into macrophage-like cells with 150 nM phorbol 12-myristate 13-acetate (PMA) (Sigma) before the experiment.
    THP-1
    suggested: None
    Huh-7 cells were subsequently lysed with 50 μL lysis reagent (Promega), and 30 μL lysates were transferred to 96-well Costar flat-bottom luminometer plates (Corning Costar) for the detection of relative light units using the Firefly Luciferase Assay Kit (Promega) with an Ultra 384 luminometer (Tecan).
    Huh-7
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Mice: 6-8 weeks old, male, specific-pathogen-free (SPF) C57BL/6 mice were inoculated with VSP, IDLV, or PBS by foot-pad injection.
    C57BL/6
    suggested: None
    Software and Algorithms
    SentencesResources
    A nonlinear regression analysis was performed on the resulting curves using Prism (GraphPad) to calculate half-maximal inhibitory concentration (EC50) values.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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.
    • 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.

  2. Version published to 10.1101/2020.05.14.093054v1 on bioRxiv