Sequential Delivery of Live Attenuated Influenza Vaccine and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the Ferret Model Can Reduce SARS-CoV-2 Shedding and Does Not Result in Enhanced Lung Pathology

  1. Kathryn A Ryan
  2. Katarzyna E Schewe
  3. Jonathan Crowe
  4. Susan A Fotheringham
  5. Yper Hall
  6. Richard Humphreys
  7. Anthony C Marriott
  8. Jemma Paterson
  9. Emma Rayner
  10. Francisco J Salguero
  11. Robert J Watson
  12. Catherine J Whittaker
  13. Miles W Carroll
  14. Oliver Dibben

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Cocirculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses could pose unpredictable risks to health systems globally, with recent studies suggesting more severe disease outcomes in coinfected patients. The initial lack of a readily available coronavirus disease 2019 (COVID-19) vaccine has reinforced the importance of influenza vaccine programs during the COVID-19 pandemic. Live attenuated influenza vaccine (LAIV) is an important tool in protecting against influenza, particularly in children. However, it is unknown whether LAIV administration influences the outcomes of acute SARS-CoV-2 infection or disease. To investigate this, quadrivalent LAIV was administered to ferrets 3 days before or after SARS-CoV-2 infection. LAIV administration did not exacerbate the SARS-CoV-2 disease course or lung pathology with either regimen. In addition, LAIV administered before SARS-CoV-2 infection significantly reduced SARS-CoV-2 replication and shedding in the upper respiratory tract. This study demonstrated that LAIV administration in close proximity to SARS-CoV-2 infection does not exacerbate mild disease and can reduce SARS-CoV-2 shedding.

Article activity feed

  1. Version published to 10.1093/infdis/jiab594
  2. ScreenIT

    SciScore for 10.1101/2021.02.01.429110: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All experimental work was conducted under the authority of a UK Home Office approved project license that had been subject to local ethical review at PHE Porton Down by the Animal Welfare and Ethical Review Body (AWERB) as required by the Home Office Animals (Scientific Procedures) Act 1986.
    RandomizationFerrets were confirmed seronegative for circulating H1N1, H3N2, and B viruses by hemagglutination inhibition (HAI) assay and randomly assigned to study groups.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableTwenty-four healthy, female ferrets (
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cells and viruses: SARS-CoV-2 strain Victoria/01/2020 44 was generously provided by The Doherty Institute, Melbourne, Australia at P1 after primary growth in Vero/hSLAM cells and subsequently passaged twice at Public Health England (PHE) Porton in Vero/hSLAM cells (ECACC 04091501).
    Vero/hSLAM
    suggested: ECACC Cat# 04091501, RRID:CVCL_L037)
    Virus titre of the challenge stocks was determined by plaque assay on Vero/E6 cells (ECACC 85020206).
    Vero/E6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Madin–Darby canine kidney (MDCK) used in FFA, were obtained from American Type Culture Collection (ATCC) and passaged fewer than 20 times prior to use in analytical tests.
    MDCK
    suggested: None
    Software and Algorithms
    SentencesResources
    Whole genome sequencing was performed on the P3 challenge stock using both Nanopore and Illumina as described previously 45.
    Nanopore
    suggested: None
    All statistical analysis was carried out in JMP v14.3 (SAS Institute Inc.).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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 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 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 10.1101/2021.02.01.429110 on bioRxiv