title: The SARS-CoV ferret model in an infection-challenge study.
abstract: Phase I human clinical studies involving therapeutics for emerging and biodefense pathogens with low incidence, such as the severe acute respiratory syndrome coronavirus (SARS-CoV), requires at a minimum preclinical evaluation of efficacy in two well-characterized and robust animal models. Thus, a ferret SARS-CoV model was evaluated over a period of 58 days following extensive optimization and characterization of the model in order to validate clinical, histopathological, virological and immunological endpoints. Ferrets that were infected intranasally with 10(3) TCID50 SARS-CoV showed higher body temperature (2-6 d.p.i.), sneezing (5-10 d.p.i.), lesions (5-7 d.p.i.) and decreased WBC/lymphocytes (2-5 d.p.i.). SARS-CoV was detected up to 7 d.p.i. in various tissues and excreta, while neutralizing antibody titers rose at 7 d.p.i. and peaked at 14 d.p.i. At 29 d.p.i., one group was challenged with 10(3) TCID50 SARS-CoV, and an anamnestic response in neutralizing antibodies was evident with no detectable virus. This study supports the validity of the ferret model for use in evaluating efficacy of potential therapeutics to treat SARS.
authors.affiliation: Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, AL, USA.
authors.forename: Yong-Kyu
authors.initials: YK
authors.lastname: Chu
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Ali
authors.forename: Fuli
authors.initials: F
authors.lastname: Jia
authors.forename: Qianjun
authors.initials: Q
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Kelvin
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Couch
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Harrod
authors.forename: Julie A
authors.initials: JA
authors.lastname: Hutt
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cameron
authors.forename: Susan R
authors.initials: SR
authors.lastname: Weiss
authors.forename: Colleen B
authors.initials: CB
authors.lastname: Jonsson
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001831:Body Temperature; D004195:Disease Models, Animal; D005289:Ferrets; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology / Q000821:virology; D018655:Lymphocyte Count; D008297:Male; D009296:Nasal Cavity / Q000821:virology; D009500:Neutralization Tests; D010614:Pharynx / Q000821:virology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000821:virology*
chemical_list: D000914:Antibodies, Viral