Virus-Like Particles Are Efficient Tools for Boosting mRNA-Induced Antibodies

  1. Anne-Cathrine S. Vogt
  2. Lukas Jörg
  3. Byron Martina
  4. Pascal S. Krenger
  5. Xinyue Chang
  6. Andris Zeltins
  7. Monique Vogel
  8. Mona O. Mohsen
  9. Martin F. Bachmann

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Abstract

mRNA based vaccines against COVID-19 have proven most successful at keeping SARS-CoV-2 pandemic at bay in many countries. Recently, there is an increased interest in heterologous prime-boost vaccination strategies for COVID-19 to maintain antibody responses for the control of continuously emerging SARS-CoV-2 variants of concern (VoCs) and to overcome other obstacles such as supply shortage, costs and reduced safety issues or inadequatly induced immune-responses. In this study, we investigated the antibody responses induced by heterologous prime-boost with vaccines based on mRNA and virus-like particles (VLPs). The VLP-based mCuMV TT -RBM vaccine candidate and the approved mRNA-1273 vaccine were used for this purpose. We find that homologous prime boost regimens with either mRNA or VLP induced high levels of high avidity antibodies. Optimal antibody responses were, however, induced by heterologous regimens both for priming with mRNA and boosting with VLP and vice versa, priming with VLP and boosting with mRNA. Thus, heterologous prime boost strategies may be able to optimize efficacy and economics of novel vaccine strategies.

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  1. Version published to 10.3389/fimmu.2022.864718
  2. ScreenIT

    SciScore for 10.1101/2021.12.20.473421: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variable4.1. Mice: In vivo experiments were performed using 8-12 weeks-old female, BALB/cOlaHsd mice purchased from Envigo (Amsterdam, Netherlands).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Enzyme-linked immunosorbant assay (ELISA): To determine the total IgG antibodies against the vaccine mCuMVTT-RBM as well as mRNA-1273 in sera of vaccinated mice, ELISA plates (96 well half-area ELISA plates; Costar, Corning, Catalog # 3690) were coated with SARS-CoV-2 RBD (wildtype) at a concentration of 1μg/ml overnight at 4°C.
    total IgG
    suggested: None
    Detecting RBD-specific IgGs against mutated RBDs was carried out in a similar way. 4.6. Avidity (ELISA): To test IgG antibody avidity against RBD protein, threefold serial dilutions of 1/20 diluted mice sera, were added to ELISA plates (96 well half-area ELISA plates; Costar, Corning, Catalog # 3690) coated over night at 4°C with 1μg/ml RBD.
    test IgG
    suggested: None
    Cytopathic effect-based neutralization assay (CPE): To determine the neutralizing ability and capacity of vaccine induced antibodies a CPE assay was performed using wild-type SARS-CoV-2 (SARS-CoV-2/ABS/NL20) and delta Strain.
    SARS-CoV-2/ABS/NL20
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Expression and purification of RBD: SARS-CoV-2 RBDwildtype, was cloned as a synthetic gene into pTWIST-CMV-BetaGlobin-WPRE-Neo vector (Twist Biosciences, CA, USA) and expressed in HEK293F cells through the Expi293 system (ThermoFisher Scientific, MA, USA).
    HEK293F
    suggested: None
    The mixture has been added on a monolayer of Vero cells and incubated again for 37°C for 4 days.
    Vero
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    4.1. Mice: In vivo experiments were performed using 8-12 weeks-old female, BALB/cOlaHsd mice purchased from Envigo (Amsterdam, Netherlands).
    BALB/cOlaHsd
    suggested: RRID:MGI:5653315)
    Recombinant DNA
    SentencesResources
    Expression and purification of RBD: SARS-CoV-2 RBDwildtype, was cloned as a synthetic gene into pTWIST-CMV-BetaGlobin-WPRE-Neo vector (Twist Biosciences, CA, USA) and expressed in HEK293F cells through the Expi293 system (ThermoFisher Scientific, MA, USA).
    pTWIST-CMV-BetaGlobin-WPRE-Neo
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were performed using GraphPad PRISM 9.0 (
    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.
    • 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

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  3. Version published to 10.1101/2021.12.20.473421v1 on bioRxiv