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Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge

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Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA
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Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA
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School of Veterinary Medicine, Utah State University, Logan, UT 84322, USA
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Defyrus Inc., 2 Bloor Street W, Suite 2602, Toronto, Ontario, M4W 3E2, Canada
*
Author to whom correspondence should be addressed.
Viruses 2014, 6(3), 1410-1423; https://doi.org/10.3390/v6031410
Received: 7 February 2014 / Revised: 13 March 2014 / Accepted: 14 March 2014 / Published: 24 March 2014
(This article belongs to the Section Antivirals & Vaccines)
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. View Full-Text
Keywords: Rift Valley Fever Virus (RVFV); phlebovirus; bunyavirus; interferon alpha; DEF201; antiviral Rift Valley Fever Virus (RVFV); phlebovirus; bunyavirus; interferon alpha; DEF201; antiviral
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Gowen, B.B.; Ennis, J.; Bailey, K.W.; Vest, Z.; Scharton, D.; Sefing, E.J.; Turner, J.D. Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge. Viruses 2014, 6, 1410-1423.

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