Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201)
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{"title"=>"Therapy and long-term prophylaxis of vaccinia virus respiratory infections in mice with an adenovirus-vectored interferon alpha (mDEF201)", "type"=>"journal", "authors"=>[{"first_name"=>"Donald F.", "last_name"=>"Smee", "scopus_author_id"=>"7007104795"}, {"first_name"=>"Min Hui", "last_name"=>"Wong", "scopus_author_id"=>"7403908721"}, {"first_name"=>"Andrew", "last_name"=>"Russell", "scopus_author_id"=>"36982190300"}, {"first_name"=>"Jane", "last_name"=>"Ennis", "scopus_author_id"=>"36660908700"}, {"first_name"=>"Jeffrey D.", "last_name"=>"Turner", "scopus_author_id"=>"55447560800"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"80054058496", "pui"=>"362750888", "doi"=>"10.1371/journal.pone.0026330", "pmid"=>"22022603", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-80054058496", "issn"=>"19326203"}, "id"=>"e40b51d2-3ce6-3d0f-bf4a-c1a750e4015d", "abstract"=>"An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. mDEF201 was administered as a single intranasal treatment either prophylactically or therapeutically at doses of 10(6) to 10(8) plaque forming units/mouse. When the prophylactic treatment was given at 56 days prior to infection, it protected 90% of animals from death (100% protection for treatments given between 1-49 days pre-infection), with minimal weight loss occurring during infection. Surviving animals re-challenged with virus 22 days after the primary infection were protected from death, indicating that mDEF201 did not compromise the immune response against the initial infection. Post-exposure therapy was given between 6-24 h after vaccinia virus exposure and protection was afforded by a 10(8) dose of mDEF201 given at 24 h, whereas a 10(7) dose was effective up to 12 h. Comparisons were made of the ability of mDEF201, given either 28 or 1 day prior to infection, to inhibit tissue virus titers and lung infection parameters. Lung, liver, and spleen virus titers were inhibited to nearly the same extent by either treatment, as were lung weights and lung hemorrhage scores (indicators of pneumonitis). Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. In contrast, viral titers and lung infection parameters were high in the placebo group on day 5 of the infection. These results demonstrate the long-acting prophylactic and treatment capacity of mDEF201 to combat vaccinia virus infections.", "link"=>"http://www.mendeley.com/research/therapy-longterm-prophylaxis-vaccinia-virus-respiratory-infections-mice-adenovirusvectored-interfero", "reader_count"=>7, "reader_count_by_academic_status"=>{"Student > Ph. D. Student"=>4, "Student > Master"=>1, "Professor"=>1, "Researcher"=>1}, "reader_count_by_user_role"=>{"Student > Ph. D. Student"=>4, "Student > Master"=>1, "Professor"=>1, "Researcher"=>1}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>5, "Veterinary Science and Veterinary Medicine"=>1, "Agricultural and Biological Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/724856"], "description"=>"<p>(A) Experiment 1, primary infection, (B) Experiment 1, reinfection, (C) Experiment 2, primary infection, (D) Experiment 2, reinfection. Intranasal treatments with mDEF201 (10<sup>7</sup> PFU/mouse) were given one time only on the indicated day prior to virus exposure. In Experiment 1 the primary intranasal challenge was 1×10<sup>5</sup> PFU of virus. Since this challenge dose failed to cause 100% mortality (as mice age their susceptibility to infection wanes), the primary virus challenge dose was increased to 2.5×10<sup>5</sup> PFU of virus for Experiment 2. Reinfection of both sets of mice was performed intranasally with 5×10<sup>5</sup> PFU of virus. The data accompany those of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026330#pone-0026330-t002\" target=\"_blank\">Table 2</a>. Thus, the initial number of mice per group for each figure corresponds to the total number per group in the table.</p>", "links"=>[], "tags"=>["prophylaxis", "mdef201", "percent", "weights", "mice", "vaccinia", "respiratory"], "article_id"=>395198, "categories"=>["Virology", "Microbiology", "Immunology"], "users"=>["Donald F. Smee", "Min-Hui Wong", "Andrew Russell", "Jane Ennis", "Jeffrey D. Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026330.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_prophylaxis_with_mDEF201_on_percent_body_weights_of_mice_during_vaccinia_virus_WR_strain_respiratory_infections_/395198", "title"=>"Effects of prophylaxis with mDEF201 on percent body weights of mice during vaccinia virus (WR strain) respiratory infections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:49:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/725000"], "description"=>"<p>(A) Lung virus titer, (B) liver virus titer, (C) lung weight, (D) spleen virus titer, (E) lung hemorrhage score, (F) snout virus titer. Intranasal treatments with mDEF201 (10<sup>7</sup> PFU/mouse) were given one time only on the indicated day prior to intranasal virus exposure (2.5×10<sup>5</sup> PFU). There were no survivors in the placebo group on day 7 for data determinations. This experiment was conducted concurrently with the second experiment in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026330#pone-0026330-t002\" target=\"_blank\">Table 2</a>. Each data point represents the mean for five animals per group.</p>", "links"=>[], "tags"=>["prophylaxis", "mdef201", "-28", "-1", "parameters", "mice", "infected", "intranasally", "vaccinia"], "article_id"=>395339, "categories"=>["Virology", "Microbiology", "Immunology"], "users"=>["Donald F. Smee", "Min-Hui Wong", "Andrew Russell", "Jane Ennis", "Jeffrey D. Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026330.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_prophylaxis_with_mDEF201_given_on_day_28_or_day_1_on_infection_parameters_in_mice_infected_intranasally_with_vaccinia_virus_WR_strain_/395339", "title"=>"Effects of prophylaxis with mDEF201 given on day -28 or day -1 on infection parameters in mice infected intranasally with vaccinia virus (WR strain).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:50:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/725065"], "description"=>"<p>Intranasal treatments with mDEF201 (10<sup>8</sup> PFU/mouse) were given one time. Cidofovir (100 mg/kg/day) was administered by intraperitoneal route once a day for two days. Test materials were given at the time indicated after intranasal virus exposure (1×10<sup>5</sup> PFU). The data accompany those of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026330#pone-0026330-t003\" target=\"_blank\">Table 3</a> (body weight results of treatment with mDEF208 at 10<sup>7</sup> PFU/mouse are not shown). Thus, the initial number of mice per group for each figure corresponds to the total number per group in the table.</p>", "links"=>[], "tags"=>["mdef201", "cidofovir", "percent", "weights", "mice", "vaccinia", "respiratory"], "article_id"=>395414, "categories"=>["Virology", "Microbiology", "Immunology"], "users"=>["Donald F. Smee", "Min-Hui Wong", "Andrew Russell", "Jane Ennis", "Jeffrey D. Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026330.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_therapy_with_mDEF201_and_cidofovir_on_percent_body_weights_of_mice_during_a_vaccinia_virus_WR_strain_respiratory_infection_/395414", "title"=>"Effects of therapy with mDEF201 and cidofovir on percent body weights of mice during a vaccinia virus (WR strain) respiratory infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:50:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/725174"], "description"=>"a<p>The mDEF201 intranasal dose of 10<sup>7</sup> PFU/mouse was given only once. All animals not receiving mDEF201 on day -1 were treated intranasally with saline on that day.</p>b<p>Relative to the primary infection. In Experiment 1 the primary intranasal challenge was 1×10<sup>5</sup> PFU of virus. Since this challenge dose failed to cause 100% mortality (as mice age their susceptibility to infection wanes), the primary virus challenge dose for Experiment 2 was increased to 2.5×10<sup>5</sup> PFU. Reinfection of both sets of mice was performed intranasally with 5×10<sup>5</sup> PFU of virus.</p>c<p>Uninfected, untreated for the primary infection, but infected at 22 days.</p><p>**P<0.01.</p><p>***P<0.001, compared to placebo (primary infection) or naïve control (reinfection).</p>", "links"=>[], "tags"=>["prophylaxis", "mdef201", "mice", "respiratory", "reinfection", "vaccinia"], "article_id"=>395520, "categories"=>["Virology", "Microbiology", "Immunology"], "users"=>["Donald F. Smee", "Min-Hui Wong", "Andrew Russell", "Jane Ennis", "Jeffrey D. Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026330.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_extended_prophylaxis_with_mDEF201_on_survival_of_mice_from_primary_respiratory_infection_and_reinfection_with_vaccinia_virus_WR_strain_/395520", "title"=>"Effects of extended prophylaxis with mDEF201 on survival of mice from primary respiratory infection and reinfection with vaccinia virus (WR strain).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 13:51:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/725214"], "description"=>"a<p>The doses of mDEF201 are in PFU/mouse units, whereas the dose of cidofovir is in mg/kg/day units. mDEF201 was given as a single intranasal treatment, as was the placebo Cidofovir was administered by intraperitoneal route once a day for two days. For consistency with the other groups, the cidofovir group also received intranasal saline at 24 h.</p>b<p>Mean day of death for mice that died on or before day 21 of the infection. The mice were inoculated intranasally with 1×10<sup>5</sup> PFU of virus to initiate the infection.</p><p>**P<0.01.</p><p>***P<0.001, compared to placebo.</p>", "links"=>[], "tags"=>["mdef201", "cidofovir", "mice", "vaccinia", "respiratory"], "article_id"=>395566, "categories"=>["Virology", "Microbiology", "Immunology"], "users"=>["Donald F. Smee", "Min-Hui Wong", "Andrew Russell", "Jane Ennis", "Jeffrey D. Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026330.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_therapy_with_mDEF201_and_cidofovir_on_survival_of_mice_from_a_vaccinia_virus_WR_strain_respiratory_infection_/395566", "title"=>"Effects of therapy with mDEF201 and cidofovir on survival of mice from a vaccinia virus (WR strain) respiratory infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 13:51:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/725249"], "description"=>"a<p>mDEF201 and empty vector are PFU/mouse doses, whereas the dose of cidofovir is mg/kg/day. mDEF201, the Ad-5 empty vector, and the placebo groups were given single intranasal treatments. Cidofovir was administered by intraperitoneal route once a day for two days. For consistency with the other groups, the cidofovir group also received saline intranasally at −24 h.</p>b<p>Relative to intranasal virus exposure (1×10<sup>5</sup> PFU).</p>c<p>Mean day of death of animals that died on or before day 21 of the infection.</p><p>*P<0.05.</p><p>**P<0.01.</p><p>***P<0.001, compared to placebo.</p>", "links"=>[], "tags"=>["mdef201", "cidofovir", "mice", "vaccinia", "respiratory"], "article_id"=>395601, "categories"=>["Virology", "Microbiology", "Immunology"], "users"=>["Donald F. Smee", "Min-Hui Wong", "Andrew Russell", "Jane Ennis", "Jeffrey D. Turner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0026330.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_treatment_with_mDEF201_and_cidofovir_on_survival_of_mice_from_a_vaccinia_virus_WR_strain_respiratory_infection_/395601", "title"=>"Effects of treatment with mDEF201 and cidofovir on survival of mice from a vaccinia virus (WR strain) respiratory infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 13:51:43"}

PMC Usage Stats | Further Information

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Relative Metric

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