The SARS-CoV ferret model in an infection–challenge study

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• 作者：Yong-Kyu Chu ; Georgia D. Ali ; Fuli Jia ; Qianjun Li ; David Kelvin ; Ronald C. Couch ; Kevin S. Harrod ; Julie A. Hutt ; Cheryl Cameron ; Susan R. Weiss ; Colleen B. Jonsson
• 关键词：SARS-CoV ; Ferret ; Animal model
• 刊名：Virology
• 出版年：2008
• 出版时间：25 April 2008
• 年：2008
• 卷：374
• 期：1
• 页码：151-163
• 全文大小：1580 K

文摘

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 10³ 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 10³ 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.