Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection
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{"title"=>"Use of recombinant adenovirus vectored consensus IFN-α to avert severe arenavirus infection", "type"=>"journal", "authors"=>[{"first_name"=>"Brian B.", "last_name"=>"Gowen", "scopus_author_id"=>"8614220900"}, {"first_name"=>"Jane", "last_name"=>"Ennis", "scopus_author_id"=>"36660908700"}, {"first_name"=>"Andrew", "last_name"=>"Russell", "scopus_author_id"=>"36982190300"}, {"first_name"=>"Eric J.", "last_name"=>"Sefing", "scopus_author_id"=>"36601454200"}, {"first_name"=>"Min Hui", "last_name"=>"Wong", "scopus_author_id"=>"7403908721"}, {"first_name"=>"Jeffrey", "last_name"=>"Turner", "scopus_author_id"=>"55447560800"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"22039436", "doi"=>"10.1371/journal.pone.0026072", "pui"=>"362825512", "issn"=>"19326203", "sgr"=>"80055061478", "scopus"=>"2-s2.0-80055061478"}, "id"=>"bad5574f-fced-3efd-aa67-4304f6cc84a2", "abstract"=>"Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α) is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens.", "link"=>"http://www.mendeley.com/research/recombinant-adenovirus-vectored-consensus-ifn%CE%B1-avert-severe-arenavirus-infection", "reader_count"=>9, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>3, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/720640"], "description"=>"<p>Animals were treated 24 hours prior to infection with a single i.n. instillation of the indicated dose of DEF201, the rAd EV control virus, or PBS placebo. (A) Survivial and (B) average weights and standard deviations of surviving animals (measured every 3<sup>rd</sup> day) are shown. ***<i>P</i><0.001 compared to placebo-treated animals. <sup>b</sup><i>P</i><0.01 and <sup>c</sup><i>P</i><0.001 compared to rAd EV-treated animals.</p>", "links"=>[], "tags"=>["pretreatment", "protects", "picv-infected", "hamsters"], "article_id"=>390994, "categories"=>["Pharmacology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Brian B. Gowen", "Jane Ennis", "Andrew Russell", "Eric J. Sefing", "Min-Hui Wong", "Jeffrey Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026072.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DEF201_pretreatment_protects_PICV_infected_hamsters_from_mortality_/390994", "title"=>"DEF201 pretreatment protects PICV-infected hamsters from mortality.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:23:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/720826"], "description"=>"<p>Animals were treated as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026072#pone-0026072-g001\" target=\"_blank\">Figure 1</a> and sacrificed on day 7 of infection for analysis of serum (A) ALT and (B) virus titer, and (C) liver and (D) spleen viral titers. *<i>P</i><0.05, **<i>P</i><0.01, compared to placebo-treated animals. <sup>a</sup><i>P</i><0.05, <sup>b</sup><i>P</i><0.01, compared to rAd EV-treated animals.</p>", "links"=>[], "tags"=>["prophylaxis", "limits", "viral", "loads", "picv-infected"], "article_id"=>391183, "categories"=>["Pharmacology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Brian B. Gowen", "Jane Ennis", "Andrew Russell", "Eric J. Sefing", "Min-Hui Wong", "Jeffrey Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026072.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DEF201_prophylaxis_limits_liver_disease_and_viral_loads_in_PICV_infected_hamsters_/391183", "title"=>"DEF201 prophylaxis limits liver disease and viral loads in PICV-infected hamsters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:24:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/721034"], "description"=>"<p>Animals were treated i.n. with a single dose 10<sup>8</sup> pfu of DEF201, the rAd EV control virus, or PBS placebo 7 or 14 days prior to PICV infection. Animal weights were measured two weeks prior to, and at the time of, PICV challenge. The effect of 7-day and 14-day pretreatments on A) weight change over the two-week period prior to PICV challenge and the extended PICV prophylaxis efficacy data for the B) 7-day and C) 14-day pretreatments are shown. ***<i>P</i><0.001 compared to respective placebo-treated animals. <sup>b</sup><i>P</i><0.01, <sup>c</sup><i>P</i><0.001 compared to respective rAd EV-treated animals.</p>", "links"=>[], "tags"=>["pre-exposure", "prophylaxis", "protects", "hamsters", "lethal", "picv"], "article_id"=>391384, "categories"=>["Pharmacology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Brian B. Gowen", "Jane Ennis", "Andrew Russell", "Eric J. Sefing", "Min-Hui Wong", "Jeffrey Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026072.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DEF201_extended_pre_exposure_prophylaxis_protects_hamsters_from_lethal_PICV_challenge_/391384", "title"=>"DEF201 extended pre-exposure prophylaxis protects hamsters from lethal PICV challenge.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:26:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/721165"], "description"=>"<p>Animals were treated as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026072#pone-0026072-g003\" target=\"_blank\">Figure 3</a>, 7 days (A, C, E, G) or 14 days (B, D, F, H) prior to PICV challenge, and sacrificed on day 7 of infection for analysis of serum (A, B) ALT and (C, D) virus titers, and (E, F) liver and (G, H) spleen viral titers. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 compared to placebo-treated animals. <sup>a</sup><i>P</i><0.05, <sup>b</sup><i>P</i><0.01, <sup>c</sup><i>P</i><0.001 compared to rAd EV-treated animals.</p>", "links"=>[], "tags"=>["pre-exposure", "prophylaxis", "limits", "viral", "loads", "picv-infected"], "article_id"=>391519, "categories"=>["Pharmacology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Brian B. Gowen", "Jane Ennis", "Andrew Russell", "Eric J. Sefing", "Min-Hui Wong", "Jeffrey Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026072.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DEF201_extended_pre_exposure_prophylaxis_limits_liver_disease_and_viral_loads_in_PICV_infected_hamsters_/391519", "title"=>"DEF201 extended pre-exposure prophylaxis limits liver disease and viral loads in PICV-infected hamsters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:26:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/721260"], "description"=>"<p>Animals were treated with a single i.n. dose of 10<sup>8</sup> pfu of DEF201 or the rAd EV control 24 h prior to infection, or 6, 24, or 48 h post infection. The dashed lines represent the 1<sup>st</sup> and 2<sup>nd</sup> challenges of the animals with PICV on day 0 and 28 of the experiment, respectively. For the initial infection, **<i>P</i><0.01, ***<i>P</i><0.001 compared to respective rAd EV-treated controls. For the second infection, sham-infected animals from the 1<sup>st</sup> infection were challenged with PICV and compared to groups of surviving animals; <sup>a</sup><i>P</i><0.05, <sup>b</sup><i>P</i><0.01, <sup>c</sup><i>P</i><0.001.</p>", "links"=>[], "tags"=>["def201", "post-exposure-treatment", "protects", "picv-infected", "hamsters"], "article_id"=>391612, "categories"=>["Pharmacology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Brian B. Gowen", "Jane Ennis", "Andrew Russell", "Eric J. Sefing", "Min-Hui Wong", "Jeffrey Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026072.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Early_DEF201_post_exposure_treatment_protects_PICV_infected_hamsters_from_mortality_/391612", "title"=>"Early DEF201 post-exposure-treatment protects PICV-infected hamsters from mortality.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:27:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/721374"], "description"=>"<p>Animals were treated as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026072#pone-0026072-g005\" target=\"_blank\">Figure 5</a> and sacrificed on day 7 of infection for analysis of serum (A) ALT and (B) virus titer, and (C) liver and (D) spleen viral titers. *<i>P</i><0.05, ***<i>P</i><0.001 compared to rAd EV-treated animals.</p>", "links"=>[], "tags"=>["def201", "post-exposure", "limits", "viral", "loads", "picv-infected"], "article_id"=>391725, "categories"=>["Pharmacology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Brian B. Gowen", "Jane Ennis", "Andrew Russell", "Eric J. Sefing", "Min-Hui Wong", "Jeffrey Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026072.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Early_DEF201_post_exposure_treatment_limits_liver_disease_and_viral_loads_in_PICV_infected_hamsters_/391725", "title"=>"Early DEF201 post-exposure treatment limits liver disease and viral loads in PICV-infected hamsters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:27:46"}

PMC Usage Stats | Further Information

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Relative Metric

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