A Potential Novel COVID-19 Vaccine With RBD-HR1/HR2 Hexamer Structure

  1. Hongbo Liu
  2. Xiang Gao
  3. Guoyong Wang
  4. Jianjun Zhang
  5. Jiajie Zhou
  6. Tingting Wei
  7. Yu Zhang
  8. Yujiao Liu
  9. Jinhua Piao
  10. Qiulei Zhang
  11. Yayuan Wang
  12. Xin Ma
  13. Xiaoting Zhu
  14. Yikun Rao
  15. Wenjuan Xia
  16. Heng Xie
  17. Wei Zhang

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Abstract

The COVID-19 pandemic and the continued spreading of the SARS-CoV-2 variants have brought a grave public health consequence and severely devastated the global economy with recessions. Vaccination is considered as one of the most promising and efficient methods to end the COVID-19 pandemic and mitigate the disease conditions if infected. Although a few vaccines have been developed with an unprecedented speed, scientists around the world are continuing pursuing the best possible vaccines with innovations. Comparing to the expensive mRNA vaccines and attenuated/inactivated SARS-CoV-2 vaccines, recombinant protein vaccines have certain advantages, including their safety (non-virus components), potential stronger immunogenicity, broader protection, ease of scaling-up production, reduced cost, etc. In this study, we reported a novel COVID-19 vaccine generated with RBD-HR1/HR2 hexamer that was creatively fused with the RBD domain and heptad repeat 1 (HR1) or heptad repeat 2 (HR2) to form a dumbbell-shaped hexamer to target the spike S1 subunit. The novel hexamer COVID-19 vaccine induced high titers of neutralizing antibody in mouse studies (>100,000), and further experiments also showed that the vaccine also induced an alternative antibody to the HR1 region, which probably alleviated the drop of immunogenicity from the frequent mutations of SARS-CoV-2.

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    SciScore for 10.1101/2021.10.28.465226: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablePseudotyped-virus neutralization assay: Mice were divided into seven groups with 8 female mice in each group and alhydrogel adjuvant (1.25 mg/ml, InvivoGen) was used for the animal study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Experimental Models: Organisms/Strains
    SentencesResources
    In this study, the final protein concentration was diluted into 0.1 mg/ml after mixed with the adjuvant and administrated at 10 μL per mice (BALB/c).
    BALB/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    Recombinant DNA
    SentencesResources
    Protein expression and purification: The constructs of RBD (319-550) and fusion proteins were synthesized and sub-cloned into pZD vector between EcoRI and HindIII.
    pZD
    suggested: None
    Software and Algorithms
    SentencesResources
    Bright-Lumi™ kit was used for fluorescence detection and the final IC50 (50% neutralization) was calculated on GraphPad Prism.
    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: 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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.10.28.465226v1 on bioRxiv