title: Single-dose intranasal administration with mDEF201 (adenovirus vectored mouse interferon-alpha) confers protection from mortality in a lethal SARS-CoV BALB/c mouse model.
abstract: Interferons (IFNs) are a first line of defense against viral infection. Herein we describe the use of an adenovirus vectored mouse IFN alpha gene (mDEF201) as a prophylactic and treatment countermeasure in a SARS-CoV-infected BALB/c mouse model. Complete survival protection was observed in mice given a single dose of mDEF201 administered intranasally 1, 3, 5, 7, or 14 days prior to lethal SARS-CoV challenge (p<0.001), and body weights of these treated mice were unaffected by the challenge. In addition, low doses of mDEF201 protected lungs in a dose dependent manner as measured by a reduction in gross pathology. Intranasal treatment with mDEF201 ranging from 10(6) to 10(8)PFU significantly protected mice against a lethal SARS-CoV infection in a dose dependent manner up to 12h post infection (p<0.001). The data suggest that mDEF201 is a new class of antiviral agent further development as treatment for SARS-CoV infections.
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Science, 5600 Old Main Hill, Logan, Utah State University, Logan, UT 84322, USA.
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Kumaki
authors.forename: Jane
authors.initials: J
authors.lastname: Ennis
authors.forename: Ramtin
authors.initials: R
authors.lastname: Rahbar
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Turner
authors.forename: Miles K
authors.initials: MK
authors.lastname: Wandersee
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Bailey
authors.forename: Zachary G
authors.initials: ZG
authors.lastname: Vest
authors.forename: Jason R
authors.initials: JR
authors.lastname: Madsen
authors.forename: Joseph K-K
authors.initials: JK
authors.lastname: Li
authors.forename: Dale L
authors.initials: DL
authors.lastname: Barnard
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000276:immunology; D001688:Biological Products / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D001835:Body Weight; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D001688:Biological Products; C554327:Ifna protein, mouse; D016898:Interferon-alpha