title: Single-dose intranasal treatment with DEF201 (adenovirus vectored consensus interferon) prevents lethal disease due to Rift Valley fever virus challenge.
abstract: Rift Valley fever virus (RVFV) causes severe disease in humans and ungulates. The virus can be transmitted by mosquitoes, direct contact with infected tissues or fluids, or aerosol, making it a significant biological threat for which there is no approved vaccine or therapeutic. Herein we describe the evaluation of DEF201, an adenovirus-vectored interferon alpha which addresses the limitations of recombinant interferon alpha protein (cost, short half-life), as a pre- and post-exposure treatment in a lethal hamster RVFV challenge model. DEF201 was delivered intranasally to stimulate mucosal immunity and effectively bypass any pre-existing immunity to the vector. Complete protection against RVFV infection was observed from a single dose of DEF201 administered one or seven days prior to challenge while all control animals succumbed within three days of infection. Efficacy of treatment administered two weeks prior to challenge was limited. Post‑exposure, DEF201 was able to confer significant protection when dosed at 30 min or 6 h, but not at 24 h post-RVFV challenge. Protection was associated with reductions in serum and tissue viral loads. Our findings suggest that DEF201 may be a useful countermeasure against RVFV infection and further demonstrates its broad-spectrum capacity to stimulate single dose protective immunity.
authors.affiliation: Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA. brian.gowen@usu.edu.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Gowen
authors.affiliation: Defyrus Inc., 2 Bloor Street W, Suite 2602, Toronto, Ontario, M4W 3E2, Canada. jane.ennis@defyrus.com.
authors.forename: Jane
authors.initials: J
authors.lastname: Ennis
authors.affiliation: Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA. kevin.bailey@aggiemail.usu.edu.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Bailey
authors.affiliation: Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA. zach.v@aggiemail.usu.edu.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Vest
authors.affiliation: Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA. dionna.scharton@aggiemail.usu.edu.
authors.forename: Dionna
authors.initials: D
authors.lastname: Scharton
authors.affiliation: Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA. biosefing@gmail.com.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sefing
authors.affiliation: Defyrus Inc., 2 Bloor Street W, Suite 2602, Toronto, Ontario, M4W 3E2, Canada. jeff.turner@defyrus.com.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Turner
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000281:Administration, Intranasal; D000825:Animal Structures / Q000821:virology; D000818:Animals; D001769:Blood / Q000821:virology; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D007155:Immunologic Factors / Q000008:administration & dosage*; D007372:Interferons / Q000008:administration & dosage*; D008647:Mesocricetus; D012295:Rift Valley Fever / Q000517:prevention & control*; D012296:Rift Valley fever virus / Q000302:isolation & purification; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D007155:Immunologic Factors; D007372:Interferons