{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:55:58Z","timestamp":1760954158175,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2014,3,24]],"date-time":"2014-03-24T00:00:00Z","timestamp":1395619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2011exposure, 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.<\/jats:p>","DOI":"10.3390\/v6031410","type":"journal-article","created":{"date-parts":[[2014,3,24]],"date-time":"2014-03-24T13:43:41Z","timestamp":1395668621000},"page":"1410-1423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge"],"prefix":"10.3390","volume":"6","author":[{"given":"Brian","family":"Gowen","sequence":"first","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA"},{"name":"School of Veterinary Medicine, Utah State University, Logan, UT 84322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Ennis","sequence":"additional","affiliation":[{"name":"Defyrus Inc., 2 Bloor Street W, Suite 2602, Toronto, Ontario, M4W 3E2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary","family":"Vest","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dionna","family":"Scharton","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Sefing","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA"},{"name":"Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Turner","sequence":"additional","affiliation":[{"name":"Defyrus Inc., 2 Bloor Street W, Suite 2602, Toronto, Ontario, M4W 3E2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"883","DOI":"10.2460\/javma.234.7.883","article-title":"Rift Valley fever virus","volume":"234","author":"Bird","year":"2009","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0749-0720(02)00029-4","article-title":"Rift valley fever","volume":"18","author":"Gerdes","year":"2002","journal-title":"Vet. Clin. North Am. Food Anim. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3390\/v3050493","article-title":"The Pathogenesis of Rift Valley Fever","volume":"3","author":"Ikegami","year":"2011","journal-title":"Viruses"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1086\/378747","article-title":"Rift Valley fever epidemic in Saudi Arabia: Epidemiological, clinical, and laboratory characteristics","volume":"37","author":"Madani","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.antiviral.2009.10.008","article-title":"Present and future arboviral threats","volume":"85","author":"Weaver","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_6","unstructured":"(2006). National Institute of Allergy and Infectious Diseases Biodefense Research Agenda for CDC Category A Agents, NIAID."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gowen, B.B., Ennis, J., Russell, A., Sefing, E.J., Wong, M.H., and Turner, J. (2011). Use of Recombinant Adenovirus Vectored Consensus IFN-\u03b1 to Avert Severe Arenavirus Infection. PLoS One.","DOI":"10.1371\/journal.pone.0026072"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1128\/AAC.01635-10","article-title":"Treatment of Yellow Fever Virus with an Adenovirus-Vectored Interferon, DEF201, in a Hamster Model","volume":"55","author":"Julander","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e26330","DOI":"10.1371\/journal.pone.0026330","article-title":"Therapy and long-term prophylaxis of vaccinia virus respiratory infections in mice with an adenovirus-vectored interferon alpha (mDEF201)","volume":"6","author":"Smee","year":"2011","journal-title":"PLoS One"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1128\/AAC.00376-12","article-title":"Extended protection against phlebovirus infection conferred by recombinant adenovirus expressing consensus interferon (DEF201)","volume":"56","author":"Gowen","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/BF01310749","article-title":"Pathogenesis of a phleboviral infection (Punta Toro virus) in golden Syrian hamsters","volume":"114","author":"Anderson","year":"1990","journal-title":"Arch. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4269\/ajtmh.2003.69.269","article-title":"Induction of severe disease in hamsters by two sandfly fever group viruses, Punta toro and Gabek Forest (Phlebovirus, Bunyaviridae), similar to that caused by Rift Valley fever virus","volume":"69","author":"Fisher","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/BF01311288","article-title":"Pathogenesis of Rift Valley fever in rhesus monkeys: Role of interferon response","volume":"110","author":"Morrill","year":"1990","journal-title":"Arch. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S815","DOI":"10.1093\/clinids\/11.Supplement_4.S815","article-title":"Prevention of Rift Valley fever in rhesus monkeys with interferon-alpha","volume":"11","author":"Morrill","year":"1989","journal-title":"Rev. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1517\/14712598.2012.694421","article-title":"Management of pegylated interferon alpha toxicity in adjuvant therapy of melanoma","volume":"12","author":"Daud","year":"2012","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1017\/S0266462305050063","article-title":"Clinical- and cost-effectiveness of pegylated interferon alfa in the treatment of chronic hepatitis C: A systematic review and economic evaluation","volume":"21","author":"Shepherd","year":"2005","journal-title":"Int. J. Technol. Assess. Health Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1093\/jac\/dkn346","article-title":"Treatment of acute hepatitis C: the success of monotherapy with (pegylated) interferon alpha","volume":"62","author":"Wiegand","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4269\/ajtmh.2010.09-0289","article-title":"Prediction, assessment of the Rift Valley fever activity in East and Southern Africa 2006\u20132008 and possible vector control strategies","volume":"83","author":"Anyamba","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1073\/pnas.0806490106","article-title":"Prediction of a Rift Valley fever outbreak","volume":"106","author":"Anyamba","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4081\/gh.2010.184","article-title":"TerraSAR-X high-resolution radar remote sensing: An operational warning system for Rift Valley fever risk","volume":"5","author":"Vignolles","year":"2010","journal-title":"Geospatial Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1099\/0022-1317-69-4-817","article-title":"Characterization of attenuated strains of Rift Valley fever virus","volume":"69","author":"Rossi","year":"1988","journal-title":"J. Gen. Virol."},{"key":"ref_22","first-page":"197","article-title":"Active and passive immunization against Rift Valley fever virus infection in Syrian hamsters","volume":"92","author":"Niklasson","year":"1984","journal-title":"Acta Pathol. Microbiol. Immunol. Scand. C"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0166-3542(86)90024-0","article-title":"Prophylaxis of Rift Valley fever with antiviral drugs, immune serum, an interferon inducer, and a macrophage activator","volume":"6","author":"Peters","year":"1986","journal-title":"Antivir. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.antiviral.2014.01.016","article-title":"Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment","volume":"104","author":"Scharton","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1051\/vetres\/2010033","article-title":"Rift Valley fever virus(Bunyaviridae: Phlebovirus): An update on pathogenesis, molecular epidemiology, vectors, diagnostics and prevention","volume":"41","author":"Pepin","year":"2010","journal-title":"Vet. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3389\/fcimb.2012.00105","article-title":"Choice of inbred rat strain impacts lethality and disease course after respiratory infection with Rift Valley Fever Virus","volume":"2","author":"Bales","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1128\/JVI.06190-11","article-title":"Development of a novel nonhuman primate model for Rift Valley fever","volume":"86","author":"Smith","year":"2012","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Scharton, D., Bailey, K.W., and Gowen, B.B. (2014). Utah State University, Logan, UT, USA. Characterization of Rift Valley fever virus infection in golden Syrian hamsters, Unpublished data.","DOI":"10.1371\/journal.pone.0116722"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e3548","DOI":"10.1371\/journal.pone.0003548","article-title":"Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice","volume":"3","author":"Croyle","year":"2008","journal-title":"PLoS One"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1128\/JVI.02864-12","article-title":"Airway delivery of an adenovirus-based Ebola virus vaccine bypasses existing immunity to homologous adenovirus in nonhuman primates","volume":"87","author":"Richardson","year":"2013","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e81","DOI":"10.1038\/emi.2013.81","article-title":"The risk of Rift Valley fever virus introduction and establishment in the United States and European Union","volume":"2","author":"Rolin","year":"2013","journal-title":"Emerg. Microbes Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.antiviral.2013.03.009","article-title":"Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge","volume":"98","author":"Gowen","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_33","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"ref_34","unstructured":"(2010). Prism software, GraphPad Software. version 5.0d."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/3\/1410\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:09:34Z","timestamp":1760216974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/6\/3\/1410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,24]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,3]]}},"alternative-id":["v6031410"],"URL":"https:\/\/doi.org\/10.3390\/v6031410","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2014,3,24]]}}}