mRNA-1273 vaccination protects against SARS-CoV-2–elicited lung inflammation in nonhuman primates

  1. Adam T. Waickman
  2. Kaitlin Victor
  3. Krista Newell
  4. Tao Li
  5. Heather Friberg
  6. Kathryn E. Foulds
  7. Mario Roederer
  8. Diane L. Bolton
  9. Jeffrey R. Currier
  10. Robert Seder

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Abstract

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  1. Version published to 10.1172/jci.insight.160039
  2. ScreenIT

    SciScore for 10.1101/2021.12.24.474132: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: Animal experiments were performed in compliance with all pertinent National Institutes of Health regulations and approval from the Animal Care and Use Committees of the Vaccine Research Center and Bioqual Inc. (Rockville, MD).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Recombinant DNA
    SentencesResources
    The resultant clusters were assigned to following cell types based on the expression of the indicated gene products: club cell (SCGB1A1, SCGB3A1), pneumocyte (PIFO, SNTN, FOXJ1), MARCO- mac (MRC1, APOE), MARCO+ mac (MRC1, APOE, MARCO), cDC.1 (CLEC9A, XCR1), cDC.2 (CD1C, CLEC10A), pDC (GZMB, IRF7), MigDC (CCR7, BIRC3),
    pDC
    suggested: RRID:Addgene_166941)
    Software and Algorithms
    SentencesResources
    Transcript alignment was performed against a Macaca mulataa reference library generated using the Cell Ranger mkref command, the Ensembl Mmul_10 top-level genome FASTA, and the corresponding Ensembl v100 gene GTF.
    Ensembl
    suggested: (Ensembl, RRID:SCR_002344)
    The resultant clusters were assigned to following cell types based on the expression of the indicated gene products: club cell (SCGB1A1, SCGB3A1), pneumocyte (PIFO, SNTN, FOXJ1), MARCO- mac (MRC1, APOE), MARCO+ mac (MRC1, APOE, MARCO), cDC.1 (CLEC9A, XCR1), cDC.2 (CD1C, CLEC10A), pDC (GZMB, IRF7), MigDC (CCR7, BIRC3), Mast cell (CPA3, GATA2), CD4+ T cell (CD3E, CD40LG), CD8+ T cell (CD3E, CD8A), and B cells (CD19, MS4A1).
    MARCO
    suggested: None
    All other statistical analysis was performed using GraphPad Prism 8 Software (GraphPad Software, La Jolla, CA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Despite these potential caveats, our findings were validated by challenge of animals with the SARS-CoV-2 B.1.351/beta variant, wherein mRNA-1273 vaccination also prevented infection-induced lung inflammation. There are some limitations of this study to consider. First, the relatively transient and self-limiting nature of SARS-CoV-2 infection and infection-elicited inflammation in macaques makes it difficult to place these observations into context of human disease. Many of the pathways, cell types, transcriptional signatures, and correlates of protection identified in our analysis have also been defined in humans with acute COVID-19, but the magnitude and timing of the events may not be homologous. Second, the route of virus administration has been shown to influence infection and inflammation in other models of SARS-CoV-2 challenge (35), so that the IN/IT route of infection used in this study may result in subtly different features of infection and inflammation than aerosol-mediated infection. In conclusion, this study defines the lower respiratory tract cellular and transcriptional signature associated with SARS-CoV-2 infection in macaques using two distinct viral variants, and identifies conserved signatures of vaccine-elicited protection from infection-attendant inflammation. These data emphasize the contribution of inflammatory/migratory DCs and macrophages to lower respiratory tract inflammation following SARS-CoV-2 infection, and define a critical relationship between ...

    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: 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 10.1101/2021.12.24.474132v1 on bioRxiv