Protection of Hamsters Challenged with SARS-CoV-2 Variants of Concern by Two Doses of MVC-COV1901 Vaccine Followed by a Single Dose of Beta Variant Version of MVC-COV1901

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Abstract

The current fight against COVID-19 is compounded by the Variants of Concern (VoCs), which can diminish the effectiveness of vaccines and potentially increase viral transmission and severity of disease. MVC-COV1901 is a protein subunit vaccine based on the prefusion SARS-CoV-2 spike protein (S-2P) and is adjuvanted with CpG 1018 and aluminum hydroxide. In this study, we used the Delta variant to challenge hamsters inoculated with S-2P from the Wuhan wildtype and the Beta variant in two-dose or three-dose regimens. Two doses of wildtype S-2P followed by the third dose of Beta variant was shown to induce the highest neutralizing antibody titer against live SARS-CoV-2 of the wildtype and all current VoCs, as well as improved neutralization against Omicron variant pseudovirus compared to three doses of wildtype S-P. All regimens of vaccination were able to protect hamsters from SARS-CoV-2 Delta variant challenge and resulted in reduced lung live virus titer and pathology. Three doses of vaccination also significantly reduced lung viral RNA titer, regardless of whether the wildtype or Beta variant S-2P was used as the third dose. Based on the immunogenicity and viral challenge data, two doses of wildtype S-2P followed by the third dose of Beta variant S-2P induced potent antibody immune responses against the VoCs.

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  1. SciScore for 10.1101/2021.09.29.462344: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: All animal work in the current study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) with animal study protocol approval number TFBS2020-019 and Academia Sinica (approval number: 20-06-1483).
    Sex as a biological variableAnimals and ethical statements: Female golden Syrian hamsters aged 8-10 weeks at study initiation were obtained from the National Laboratory Animal Center (Taipei,
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis: The analysis package in Prism 6.01 (GraphPad) was used for statistical analysis.
    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: We detected the following sentences addressing limitations in the study:
    One limitation of this study is that we have not tested the vaccine’s protection in vivo with other VoCs, so the vaccine efficacy against other VoCs is inferred from the neutralizing antibody titers. The natural course of infection among the hamsters includes convalescent state, so the model does not allow for evaluating mortality or severe disease as endpoints. T-cell functions were not evaluated, limiting the assessment of role of cellular immunity in the role of protection. Two recent studies investigated the effects of booster dose of ChAdOx1 and mRNA-1273 [9, 29]. Administration of a third dose using Beta variant version of mRNA-1273 (mRNA-1273.351) after two doses of mRNA-1273 had lower adverse events and increased immunogenicity against the Beta variant than three doses of mRNA-1273; while administration of either mRNA-1273 or mRNA1273-351 as third dose exponentially boosted immunogenicity against all variants tested compared to two doses of mRNA1273 [9]. While in ChAdOx1, the third dose induced generally less adverse events than that of first or second dose, and third dose boosted neutralization titers against the Beta and Delta variants as well as gamma-interferon levels [29]. These findings appear to corroborate our results that a third dose of vaccination could boost immune response against the virus and its variants. As an extension of phase 1 clinical trial of MVC-COV1901, the participants were administered with a booster vaccination of the original S-2P at 180 d...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04487210Active, not recruitingA Study to Evaluate the Safety and Immunogenicity of MVC-COV…


    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.