Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1

  1. Raveen Rathnasinghe
  2. Mirella Salvatore
  3. Hongyong Zheng
  4. Sonia Jangra
  5. Thomas Kehrer
  6. Ignacio Mena
  7. Michael Schotsaert
  8. Thomas Muster
  9. Peter Palese
  10. Adolfo García-Sastre

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Abstract

The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.

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  1. Version published to 10.1038/s41598-021-01780-8
  2. ScreenIT

    SciScore for 10.1101/2021.04.28.441797: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableHemizygous female K18-hACE2 mice on the C57BL/6J genetic background (Jax strain 034860), were used to conduct studies with SARS-CoV-2 in BSL3 conditions.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Vero cells, Madin-Darby bovine kidney (MDBK) cells, baby hamster kidney (BHK) cells or embryonated chicken eggs were used to propagate the following viruses as per standard protocols; Influenza A ΔNS1, hvPR8, PR8, A/WSN/33, A/X-31/H3N2, Influenza
    BHK
    suggested: None
    Madin-Darby canine kidney (MDCK) cells or Vero cells were plated to obtain confluent monolayers and plaque assays were performed as previously described and an agar overlay in DMEM-F12 including 1 μgml−1 of trypsin was used.
    Vero
    suggested: None
    MDCK, cVero and BHK cells were cultured in DMEM in the presence of 10% FBS and penicillin-streptomycin.
    MDCK
    suggested: None
    Lung homogenates derived from SARS-CoV-2 infected K18 mice were handled and titered in Vero-E6 cells as described previously74.
    Vero-E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    A2G mice were kindly provided by Dr. Heinz Arnheiter while the BALB/c and C56BL/6 mice were purchased from Taconic Farms.
    C56BL/6
    suggested: None
    Hemizygous female K18-hACE2 mice on the C57BL/6J genetic background (Jax strain 034860), were used to conduct studies with SARS-CoV-2 in BSL3 conditions.
    K18-hACE2
    suggested: RRID:IMSR_GPT:T037657)
    C57BL/6J
    suggested: None
    Lung homogenates derived from SARS-CoV-2 infected K18 mice were handled and titered in Vero-E6 cells as described previously74.
    K18
    suggested: None
    Correct size for the PCR products in A2G mice was 756 bp while it was 333 bp in BALB/c mice due to a deletion in the Mx1 gene between nucleotides 1120-154331.
    BALB/c
    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: 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

    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.

  3. Version published to 10.1101/2021.04.28.441797v1 on bioRxiv