Self-assembling SARS-CoV-2 nanoparticle vaccines targeting the S protein induces protective immunity in mice

  1. Xingjian Liu
  2. Haozhi Song
  3. Jianmin Jiang
  4. Xintao Gao
  5. Yongzhu Yi
  6. Yuting Shang
  7. Jialei Li
  8. Dan Li
  9. Zhen Zeng
  10. Yinü Li
  11. Zhifang Zhang

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Abstract

The spike (S), a homotrimer glycoprotein, is the most important antigen target in the research and development of SARS-CoV-2 vaccine. There is no doubt that fully simulating the advanced structure of this homotrimer in the subunit vaccine development strategy is the most likely way to improve the immune protective effect of the vaccine. In this study, the preparation strategies of S protein receptor-binding domain (RBD) trimer, S1 region trimer, and ectodomain (ECD) trimer nanoparticles were designed based on ferritin nanoparticle self-assembly technology. The Bombyx mori baculovirus expression system was used to prepare these three nanoparticle vaccines with high expression levels in the silkworm. The immune results of mice show that the nanoparticle vaccine prepared by this strategy can not only induce an immune response by subcutaneous administration but also effective by oral administration. Given the stability of these ferritin-based nanoparticles vaccine, easy-to-use and low-cost oral immunization strategy can make up for the vaccination blind areas caused by the shortage of ultralow-temperature equipment and medical resources in underdeveloped areas. And the oral vaccine is also a very potential candidate to cut off the spread of SARS-CoV-2 in domestic and farmed animals, especially in stray and wild animals.

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  1. Version published to 10.1101/2021.02.05.428685v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.02.05.428685: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Animal ethics statement: The mouse immunogenicity studies were performed in Biotechnology Research Institute and Institute of Animal Sciences of Chinese Academy of Agricultural Science.
    IRB: The Ethics Review Board of Biotechnology Research Institute and Institute of Animal Sciences approved this study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Goat Anti-Rabbit IgG (whole molecule) Gold antibody was obtained from Sigma Aldrich (St. Louis, MO, USA).
    Goat Anti-Rabbit IgG (whole molecule) Gold antibody
    suggested: (Sigma-Aldrich Cat# G7277, RRID:AB_259951)
    Anti-Rabbit IgG (whole molecule)
    suggested: None
    After 1 h incubation at 37°C, the plates were washed three times and added the HRP-conjugated Goat anti-mouse IgG antibody with a dilution of 1:5000.
    anti-mouse IgG
    suggested: (LSBio (LifeSpan Cat# LS-C69682-5000, RRID:AB_1653096)
    Experimental Models: Cell Lines
    SentencesResources
    HEK-293T cells was obtained from ATCC and cultured in DMEM (Thermo Fisher, Waltham, MA, USA) with 10% FBS at 37°C.
    HEK-293T
    suggested: None
    SARS-CoV-2 authentic virus neutralization assay: To assess the neutralization of the SARS-CoV-2 infection in vitro, Vero cells (5×104) were seeded in 96-well plates and grown overnight.
    Vero
    suggested: RRID:CVCL_ZW93)
    Experimental Models: Organisms/Strains
    SentencesResources
    The Escherichia coli strains Top10 and BL21 (DE3) were cultured in Luria-Bertani (LB) medium.
    Top10
    suggested: None
    Mouse study designs: Six BALB/c mice (6-8 weeks of age) were assigned in every group.
    BALB/c
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: All statistical analyses were carried out with GraphPad Prism software.
    GraphPad Prism
    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 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 15. 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 10.1101/2021.02.05.428685v1 on bioRxiv