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

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

doi:10.1016/j.virol.2007.12.032

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

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

Research output: Contribution to journal › Article › peer-review

93 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	151-163
Number of pages	13
Journal	Virology
Volume	374
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2007.12.032
Publication status	Published - Apr 25 2008
Externally published	Yes

Bibliographical note

Funding Information:
This research was supported by the NIH Contract N01-AI-30063 (P.I. C.B.J). We thank Charles Gagliano for ferret training provided for this study, Dr. Al Bartolucci for statistical analyses, Kate Buckley for careful review of all the data sets, and Richard Watson for performing SARS-CoV assays. We appreciate the discussions with Drs. Judy Hewitt and Fred Cassals in the development of the model and in review of the manuscript.

ASJC Scopus Subject Areas

Virology

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Validation Study

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10.1016/j.virol.2007.12.032

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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 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.",

author = "Chu, {Yong Kyu} and Ali, {Georgia D.} and Fuli Jia and Qianjun Li and David Kelvin and Couch, {Ronald C.} and Harrod, {Kevin S.} and Hutt, {Julie A.} and Cheryl Cameron and Weiss, {Susan R.} and Jonsson, {Colleen B.}",

note = "Funding Information: This research was supported by the NIH Contract N01-AI-30063 (P.I. C.B.J). We thank Charles Gagliano for ferret training provided for this study, Dr. Al Bartolucci for statistical analyses, Kate Buckley for careful review of all the data sets, and Richard Watson for performing SARS-CoV assays. We appreciate the discussions with Drs. Judy Hewitt and Fred Cassals in the development of the model and in review of the manuscript.",

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AU - Harrod, Kevin S.

AU - Hutt, Julie A.

AU - Cameron, Cheryl

AU - Weiss, Susan R.

AU - Jonsson, Colleen B.

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

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