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Viruses 2016, 8(7), 203; doi:10.3390/v8070203

Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures

1
Battelle Biomedical Research Center, West Jefferson, OH 43162, USA
2
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR 97239, USA
3
Biomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC 20201, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 22 June 2016 / Revised: 15 July 2016 / Accepted: 19 July 2016 / Published: 22 July 2016
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [3269 KB, uploaded 22 July 2016]   |  

Abstract

In 2007, the United States– Food and Drug Administration (FDA) issued guidance concerning animal models for testing the efficacy of medical countermeasures against variola virus (VARV), the etiologic agent for smallpox. Ectromelia virus (ECTV) is naturally-occurring and responsible for severe mortality and morbidity as a result of mousepox disease in the murine model, displaying similarities to variola infection in humans. Due to the increased need of acceptable surrogate animal models for poxvirus disease, we have characterized ECTV infection in the BALB/c mouse. Mice were inoculated intranasally with a high lethal dose (125 PFU) of ECTV, resulting in complete mortality 10 days after infection. Decreases in weight and temperature from baseline were observed eight to nine days following infection. Viral titers via quantitative polymerase chain reaction (qPCR) and plaque assay were first observed in the blood at 4.5 days post-infection and in tissue (spleen and liver) at 3.5 days post-infection. Adverse clinical signs of disease were first observed four and five days post-infection, with severe signs occurring on day 7. Pathological changes consistent with ECTV infection were first observed five days after infection. Examination of data obtained from these parameters suggests the ECTV BALB/c model is suitable for potential use in medical countermeasures (MCMs) development and efficacy testing. View Full-Text
Keywords: ectromelia; BALB/c; smallpox; surrogate model; vaccine; medical countermeasure; antiviral ectromelia; BALB/c; smallpox; surrogate model; vaccine; medical countermeasure; antiviral
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Garver, J.; Weber, L.; Vela, E.M.; Anderson, M.; Warren, R.; Merchlinsky, M.; Houchens, C.; Rogers, J.V. Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures. Viruses 2016, 8, 203.

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