title: Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures.
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.
authors.affiliation: Battelle Biomedical Research Center, West Jefferson, OH 43162, USA. garverj@battelle.org.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Garver
authors.affiliation: Battelle Biomedical Research Center, West Jefferson, OH 43162, USA. weberl@battelle.org.
authors.forename: Lauren
authors.initials: L
authors.lastname: Weber
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR 97239, USA. vela@ohsu.edu.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Vela
authors.affiliation: Battelle Biomedical Research Center, West Jefferson, OH 43162, USA. andersonms@battelle.org.
authors.forename: Mike
authors.initials: M
authors.lastname: Anderson
authors.affiliation: Biomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC 20201, USA. richard.warren@hhs.gov.
authors.forename: Richard
authors.initials: R
authors.lastname: Warren
authors.affiliation: Biomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC 20201, USA. michael.merchlinsky@hhs.gov.
authors.forename: Michael
authors.initials: M
authors.lastname: Merchlinsky
authors.affiliation: Biomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC 20201, USA. christopher.houchens@hhs.gov.
authors.forename: Christopher
authors.initials: C
authors.lastname: Houchens
authors.affiliation: Battelle Biomedical Research Center, West Jefferson, OH 43162, USA. rogersjv@battelle.org.
authors.forename: James V
authors.initials: JV
authors.lastname: Rogers
mesh_terms: D000281:Administration, Intranasal; D032761:Animal Experimentation; D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D004481:Ectromelia virus / Q000302:isolation & purification*; D004482:Ectromelia, Infectious / Q000473:pathology* / Q000821:virology; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D012376:Rodent Diseases / Q000473:pathology* / Q000821:virology; D016019:Survival Analysis; D013997:Time Factors; D019562:Viral Load; D010948:Viral Plaque Assay
keywords: BALB/c; antiviral; ectromelia; medical countermeasure; smallpox; surrogate model; vaccine