The SARS-CoV ferret model in an infection-challenge study.
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.
Chu
Yong-Kyu
YK
Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, AL, USA.
Ali
Georgia D
GD
Jia
Fuli
F
Li
Qianjun
Q
Kelvin
David
D
Couch
Ronald C
RC
Harrod
Kevin S
KS
Hutt
Julie A
JA
Cameron
Cheryl
C
Weiss
Susan R
SR
Jonsson
Colleen B
CB
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*
D000914:Antibodies, Viral