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Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

Author

Listed:
  • Kathryn A. Ryan

    (National Infection Service, Public Health England (PHE))

  • Kevin R. Bewley

    (National Infection Service, Public Health England (PHE))

  • Susan A. Fotheringham

    (National Infection Service, Public Health England (PHE))

  • Gillian S. Slack

    (National Infection Service, Public Health England (PHE))

  • Phillip Brown

    (National Infection Service, Public Health England (PHE))

  • Yper Hall

    (National Infection Service, Public Health England (PHE))

  • Nadina I. Wand

    (National Infection Service, Public Health England (PHE))

  • Anthony C. Marriott

    (National Infection Service, Public Health England (PHE))

  • Breeze E. Cavell

    (National Infection Service, Public Health England (PHE))

  • Julia A. Tree

    (National Infection Service, Public Health England (PHE))

  • Lauren Allen

    (National Infection Service, Public Health England (PHE))

  • Marilyn J. Aram

    (National Infection Service, Public Health England (PHE))

  • Thomas J. Bean

    (National Infection Service, Public Health England (PHE))

  • Emily Brunt

    (National Infection Service, Public Health England (PHE))

  • Karen R. Buttigieg

    (National Infection Service, Public Health England (PHE))

  • Daniel P. Carter

    (National Infection Service, Public Health England (PHE))

  • Rebecca Cobb

    (National Infection Service, Public Health England (PHE))

  • Naomi S. Coombes

    (National Infection Service, Public Health England (PHE))

  • Steve J. Findlay-Wilson

    (National Infection Service, Public Health England (PHE))

  • Kerry J. Godwin

    (National Infection Service, Public Health England (PHE))

  • Karen E. Gooch

    (National Infection Service, Public Health England (PHE))

  • Jade Gouriet

    (National Infection Service, Public Health England (PHE))

  • Rachel Halkerston

    (National Infection Service, Public Health England (PHE))

  • Debbie J. Harris

    (National Infection Service, Public Health England (PHE))

  • Thomas H. Hender

    (National Infection Service, Public Health England (PHE))

  • Holly E. Humphries

    (National Infection Service, Public Health England (PHE))

  • Laura Hunter

    (National Infection Service, Public Health England (PHE))

  • Catherine M. K. Ho

    (National Infection Service, Public Health England (PHE))

  • Chelsea L. Kennard

    (National Infection Service, Public Health England (PHE))

  • Stephanie Leung

    (National Infection Service, Public Health England (PHE))

  • Stephanie Longet

    (National Infection Service, Public Health England (PHE))

  • Didier Ngabo

    (National Infection Service, Public Health England (PHE))

  • Karen L. Osman

    (National Infection Service, Public Health England (PHE))

  • Jemma Paterson

    (National Infection Service, Public Health England (PHE))

  • Elizabeth J. Penn

    (National Infection Service, Public Health England (PHE))

  • Steven T. Pullan

    (National Infection Service, Public Health England (PHE))

  • Emma Rayner

    (National Infection Service, Public Health England (PHE))

  • Oliver Skinner

    (National Infection Service, Public Health England (PHE))

  • Kimberley Steeds

    (National Infection Service, Public Health England (PHE))

  • Irene Taylor

    (National Infection Service, Public Health England (PHE))

  • Tom Tipton

    (National Infection Service, Public Health England (PHE))

  • Stephen Thomas

    (National Infection Service, Public Health England (PHE))

  • Carrie Turner

    (National Infection Service, Public Health England (PHE))

  • Robert J. Watson

    (National Infection Service, Public Health England (PHE))

  • Nathan R. Wiblin

    (National Infection Service, Public Health England (PHE))

  • Sue Charlton

    (National Infection Service, Public Health England (PHE))

  • Bassam Hallis

    (National Infection Service, Public Health England (PHE))

  • Julian A. Hiscox

    (University of Liverpool)

  • Simon Funnell

    (National Infection Service, Public Health England (PHE))

  • Mike J. Dennis

    (National Infection Service, Public Health England (PHE))

  • Catherine J. Whittaker

    (National Infection Service, Public Health England (PHE))

  • Michael G. Catton

    (Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity)

  • Julian Druce

    (Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity)

  • Francisco J. Salguero

    (National Infection Service, Public Health England (PHE))

  • Miles W. Carroll

    (National Infection Service, Public Health England (PHE)
    Oxford University)

Abstract

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5–15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.

Suggested Citation

  • Kathryn A. Ryan & Kevin R. Bewley & Susan A. Fotheringham & Gillian S. Slack & Phillip Brown & Yper Hall & Nadina I. Wand & Anthony C. Marriott & Breeze E. Cavell & Julia A. Tree & Lauren Allen & Mari, 2021. "Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20439-y
    DOI: 10.1038/s41467-020-20439-y
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    Cited by:

    1. Ellen Boyd & Michelle Coombe & Natalie Prystajecky & Jessica M. Caleta & Inna Sekirov & John Tyson & Chelsea Himsworth, 2023. "Hands off the Mink! Using Environmental Sampling for SARS-CoV-2 Surveillance in American Mink," IJERPH, MDPI, vol. 20(2), pages 1-11, January.
    2. Magen E. Francis & Ethan B. Jansen & Anthony Yourkowski & Alaa Selim & Cynthia L. Swan & Brian K. MacPhee & Brittany Thivierge & Rachelle Buchanan & Kerry J. Lavender & Joseph Darbellay & Matthew B. R, 2023. "Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Julia M. Adler & Ricardo Martin Vidal & Christine Langner & Daria Vladimirova & Azza Abdelgawad & Daniela Kunecova & Xiaoyuan Lin & Geraldine Nouailles & Anne Voss & Sandra Kunder & Achim D. Gruber & , 2024. "An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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