A measles-vectored COVID-19 vaccine induces long-term immunity and protection from SARS-CoV-2 challenge in mice

  1. Phanramphoei N. Frantz
  2. Aleksandr Barinov
  3. Claude Ruffié
  4. Chantal Combredet
  5. Valérie Najburg
  6. Samaporn Teeravechyan
  7. Anan Jongkaewwattana
  8. Matthieu Prot
  9. Laurine Conquet
  10. Xavier Montagutelli
  11. Priyanka Fernandes
  12. Hélène Strick-Marchand
  13. James Di Santo
  14. Etienne Simon-Lorière
  15. Christiane Gerke
  16. Frédéric Tangy

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Abstract

In light of the expanding SARS-CoV-2 pandemic, developing efficient vaccines that can provide sufficient coverage for the world population is a global health priority. The measles virus (MV)-vectored vaccine is an attractive candidate given the measles vaccine’s extensive safety history, well-established manufacturing process, and induction of strong, long-lasting immunity. We developed an MV-based SARS-CoV-2 vaccine using either the full-length spike (S) or S2 subunit as the antigen. While the S2 antigen failed to induce neutralizing antibodies, the prefusion-stabilized, full-length S (MV-ATU2-SF-2P-dER) construct proved to be an attractive vaccine candidate, eliciting strong Th1-dominant T-cell and neutralizing antibody responses against the S antigen while minimizing reactivity to the vector itself. Neutralizing antibody titers remained high three months after homologous prime-boost immunization, and infectious virus was undetectable in all animals after challenge with a mouse-adapted SARS-CoV-2 virus.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.17.431630: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cells and viruses: Human embryonic kidney cells (HEK) 293T (ATCC CRL-3216)
    HEK
    suggested: None
    293T
    suggested: None
    , HEK293T7-NP helper cells (stably expressing MV-N and MV-P genes), African green monkey kidney cells (Vero) and Vero C1008 clone E6 (ATCC CRL-1586) were maintained at 37°C, 5% CO2 in Dulbecco’s modified Eagle medium (DMEM) (Thermo Fisher) supplemented with 5% (for Vero cells) or 10% (for HEK293T cells) heat-inactivated fetal bovine serum (FBS) (Corning), 100 units/ml of penicillin-streptomycin and 100 ug/ml of streptomycin.
    Vero C1008
    suggested: ATCC Cat# CRL-1586, RRID:CVCL_0574)
    HEK293T
    suggested: None
    Briefly, helper HEK293T7-NP cells were individually transfected with 5 µg of pTM-MVSchwartz-based SARS-CoV-2 S plasmids and 0.02 µg of pEMC-La, plasmid expressing the MV polymerase (L) gene 60.
    HEK293T7-NP
    suggested: None
    Virus growth kinetics of rMVs was studied on monolayers of Vero cells in 6-well plates.
    Vero
    suggested: None

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04357028SuspendedMeasles Vaccine in HCW

    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 35. 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.

  2. Version published to 10.1101/2021.02.17.431630 on bioRxiv