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

Nat Commun. 2021 Jan 4;12(1):81. doi: 10.1038/s41467-020-20439-y.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • COVID-19 / immunology*
  • COVID-19 Vaccines / immunology
  • COVID-19 Vaccines / pharmacology
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Female
  • Ferrets / immunology*
  • Lung / immunology
  • Lung / pathology
  • RNA, Viral / isolation & purification
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Virus Replication / drug effects
  • Virus Replication / immunology
  • Virus Shedding / drug effects
  • Virus Shedding / immunology

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • RNA, Viral