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Development and Characterization of Ectromelia Virus-Moscow in the BALB/c Mouse Model for Smallpox Therapeutic and Prophylaxis Drug Efficacy Testing Under the FDA Animal Rule

Huettner, Lauren E
http://rave.ohiolink.edu/etdc/view?acc_num=osu1397642415

Abstract Details

2014, Master of Public Health, Ohio State University, Public Health.
Variola virus (VARV) is the causative agent of smallpox and has been globally eradicated with no naturally occurring infections reported since 1977. Because Variola virus (VARV) has been eradicated from the environment, alternative animal models are used to evaluate potential treatments for smallpox. One model of smallpox utilizes intranasal (IN) inoculation of BALB/c mice with ECTV, causative agent of mousepox disease in mice, due to the genetic and disease presentation similarities between ECTV and VARV. The ECTV-mouse model reproduces many features similar to that of human smallpox including severe, acute systemic disease caused by a low virus infectious dose; lack of pulmonary involvement early in the disease progression; and a presentation of a characteristic pustular rash in mice that survive the acute phase of disease. Thus, the BALB/c mouse model was developed to characterize and study ECTV infection and pathogenesis. First, the propagation of ECTV resulted in a certified working stock of virus and the LD90 and LD50 were determined to be 32.10 PFU and < 2.44 PFU, respectively. The natural history study resulted in the characterization of the disease progression resulting from intranasal infection in BALB/c mice. The clinical parameters that provided the earliest indication of disease onset following challenge were defined, in addition to the clinical parameters that correlated with mortality and time-to-death. The final study aimed to evaluate the combination of various clinical signs of disease as reliable markers to define the onset of ECTV disease within the context clinical disease progression in the BALB/c mouse model using a combination of clinical and laboratory parameters. In all, the ECTV BALB/c mouse program resulted in a well-characterized small animal model that is suitable for use under the FDA &#x201c;Animal Rule&#x201d; in order to test the efficacy of therapeutics for smallpox.
Eric Vela, Dr (Committee Member)
Thomas Wittum, Dr (Advisor)
Mary Ellen Wewers, Dr (Committee Member)
97 p.
Biomedical Research; Public Health; Virology
Smallpox; FDA Animal Rule; Ectromelia virus; Animal Modeling

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Citations

  • Huettner, L. E. (2014). Development and Characterization of Ectromelia Virus-Moscow in the BALB/c Mouse Model for Smallpox Therapeutic and Prophylaxis Drug Efficacy Testing Under the FDA Animal Rule [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397642415

    APA Style (7th edition)

  • Huettner, Lauren. Development and Characterization of Ectromelia Virus-Moscow in the BALB/c Mouse Model for Smallpox Therapeutic and Prophylaxis Drug Efficacy Testing Under the FDA Animal Rule. 2014. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1397642415.

    MLA Style (8th edition)

  • Huettner, Lauren. "Development and Characterization of Ectromelia Virus-Moscow in the BALB/c Mouse Model for Smallpox Therapeutic and Prophylaxis Drug Efficacy Testing Under the FDA Animal Rule." Master's thesis, Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397642415

    Chicago Manual of Style (17th edition)

osu1397642415
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This open access ETD is published by The Ohio State University and OhioLINK.