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.
journal_name
Virologyjournal_title
Virologyauthors
Chu YK,Ali GD,Jia F,Li Q,Kelvin D,Couch RC,Harrod KS,Hutt JA,Cameron C,Weiss SR,Jonsson CBdoi
10.1016/j.virol.2007.12.032subject
Has Abstractpub_date
2008-04-25 00:00:00pages
151-63issue
1eissn
0042-6822issn
1096-0341pii
S0042-6822(07)00845-8journal_volume
374pub_type
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