Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge
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 th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-03-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/6/3/1410 |
| _version_ | 1818063035128872960 |
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| author | Brian B. Gowen Jane Ennis Kevin W. Bailey Zachary Vest Dionna Scharton Eric J. Sefing Jeffrey D. Turner |
| author_facet | Brian B. Gowen Jane Ennis Kevin W. Bailey Zachary Vest Dionna Scharton Eric J. Sefing Jeffrey D. Turner |
| author_sort | Brian B. Gowen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T14:13:42Z |
| format | Article |
| id | doaj.art-bb52ff433d11430cad2c3f4ac8eccb7e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-10T14:13:42Z |
| publishDate | 2014-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-bb52ff433d11430cad2c3f4ac8eccb7e2022-12-22T01:45:25ZengMDPI AGViruses1999-49152014-03-01631410142310.3390/v6031410v6031410Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus ChallengeBrian B. Gowen0Jane Ennis1Kevin W. Bailey2Zachary Vest3Dionna Scharton4Eric J. Sefing5Jeffrey D. Turner6Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADefyrus Inc., 2 Bloor Street W, Suite 2602, Toronto, Ontario, M4W 3E2, CanadaDepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADefyrus Inc., 2 Bloor Street W, Suite 2602, Toronto, Ontario, M4W 3E2, CanadaRift 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.http://www.mdpi.com/1999-4915/6/3/1410Rift Valley Fever Virus (RVFV)phlebovirusbunyavirusinterferon alphaDEF201antiviral |
| spellingShingle | Brian B. Gowen Jane Ennis Kevin W. Bailey Zachary Vest Dionna Scharton Eric J. Sefing Jeffrey D. Turner Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge Viruses Rift Valley Fever Virus (RVFV) phlebovirus bunyavirus interferon alpha DEF201 antiviral |
| title | Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge |
| title_full | Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge |
| title_fullStr | Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge |
| title_full_unstemmed | Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge |
| title_short | Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge |
| title_sort | single dose intranasal treatment with def201 adenovirus vectored consensus interferon prevents lethal disease due to rift valley fever virus challenge |
| topic | Rift Valley Fever Virus (RVFV) phlebovirus bunyavirus interferon alpha DEF201 antiviral |
| url | http://www.mdpi.com/1999-4915/6/3/1410 |
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