A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants

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Abstract

Background

With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy.

Methods

We report an mRNA-based vaccine using an engineered “hybrid” receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants.

Results

A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs.

Conclusions

These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

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  1. SciScore for 10.1101/2022.01.31.478406: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: Ethics statement: All mouse works were conducted in accordance with the “Guideline for the Care and Use of Laboratory Animals” as defined by the Council of Agriculture, Taiwan and was approved by the Institutional Animal Care and Use Committee of Academia Sinica (protocol ID: 20-05-1471).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After washing, the cells were incubated with anti-RBD polyclonal antibody (1μg/tube) at 4°C for 30 minutes.
    anti-RBD
    suggested: None
    The cells were then washed two times, followed by 30-minute incubation with PE-goat-anti-mouse IgG (H+L) antibody (Jackson ImmunoResearch, PA, USA) at 4°C.
    PE-goat-anti-mouse IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    RBD expression and binding assay: The variant-specific RBD mRNA was transfected into 293T cells via lipofectamine (Invitrogen, MA, USA) and the variant-specific RBD-LNP was transfected by directly added.
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    To test the ability of RBD binding to human ACE2 or mouse ACE2, 293T-hACE2 or 3T3-mACE2 cells were harvested and aliquoted into FACS tubes at 5×105 cells/tube.
    3T3-mACE2
    suggested: None
    The mixtures were then added to pre-seeded 293T-hACE2 cells and incubated for 3 days.
    293T-hACE2
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Animals: BALB/c mice were purchased from the National Laboratory Animal Center (Taipei, Taiwan) and maintained in a specific pathogen-free environment in the animal facilities of the Institute of Biomedical Sciences, Academia Sinica.
    BALB/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    Software and Algorithms
    SentencesResources
    The cells were washed twice and resuspended in 300 μl of staining buffer containing 7-AAD (Biolegend, CA, USA) for flow cytometry analysis (Thermo Fisher Attune NxT - 14 color analyzer, Thermo Fisher Attune NxT software v2.2, FlowJo 10.6.1).
    Thermo Fisher Attune NxT
    suggested: (Attune Nxt Nxt, RRID:SCR_019590)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    The 50% neutralization titer (NT50) was calculated by nonlinear regression using Prism software version 8.1.0 (
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad Software Inc.)
    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 14. 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.

    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.