Homologous and Heterologous Protection of Nonhuman Primates by Ebola and Sudan Virus-Like Particles
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{"title"=>"Homologous and heterologous protection of nonhuman primates by ebola and sudan virus-Like particles", "type"=>"journal", "authors"=>[{"first_name"=>"Kelly L.", "last_name"=>"Warfield", "scopus_author_id"=>"6602864764"}, {"first_name"=>"John M.", "last_name"=>"Dye", "scopus_author_id"=>"35845174100"}, {"first_name"=>"Jay B.", "last_name"=>"Wells", "scopus_author_id"=>"55435912100"}, {"first_name"=>"Robert C.", "last_name"=>"Unfer", "scopus_author_id"=>"6506999881"}, {"first_name"=>"Frederick W.", "last_name"=>"Holtsberg", "scopus_author_id"=>"57078799800"}, {"first_name"=>"Sergey", "last_name"=>"Shulenin", "scopus_author_id"=>"57078672900"}, {"first_name"=>"Hong", "last_name"=>"Vu", "scopus_author_id"=>"55246596500"}, {"first_name"=>"Dana L.", "last_name"=>"Swenson", "scopus_author_id"=>"7102254368"}, {"first_name"=>"Sina", "last_name"=>"Bavari", "scopus_author_id"=>"7003364755"}, {"first_name"=>"M. Javad", "last_name"=>"Aman", "scopus_author_id"=>"56744332200"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"603270774", "doi"=>"10.1371/journal.pone.0118881", "isbn"=>"0275-6382 (Print)\\n0275-6382 (Linking)", "pmid"=>"25793502", "issn"=>"19326203", "scopus"=>"2-s2.0-84925970450", "sgr"=>"84925970450"}, "id"=>"452bbce3-46ea-346c-a909-6c1277061b6b", "abstract"=>"Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components.", "link"=>"http://www.mendeley.com/research/homologous-heterologous-protection-nonhuman-primates-ebola-sudan-viruslike-particles", "reader_count"=>40, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Librarian"=>4, "Researcher"=>9, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>3, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Librarian"=>4, "Researcher"=>9, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>3, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Agricultural and Biological Sciences"=>6, "Arts and Humanities"=>1, "Philosophy"=>1, "Veterinary Science and Veterinary Medicine"=>3, "Chemistry"=>2, "Engineering"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Nursing and Health Professions"=>4, "Medicine and Dentistry"=>8, "Neuroscience"=>1, "Psychology"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Unspecified"=>{"Unspecified"=>5}, "Environmental Science"=>{"Environmental Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Engineering"=>{"Engineering"=>2}, "Chemistry"=>{"Chemistry"=>2}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Philosophy"=>{"Philosophy"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>3}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1965216"], "description"=>"<div><p>Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the <i>Ebolavirus</i> genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components.</p></div>", "links"=>[], "tags"=>["VP 40 matrix protein", "Several vaccine platforms", "TAFV", "EBOV nonhuman primate model", "protection", "RAVV", "infection", "SUDV", "Ta ï Forest virus", "MARV VLPs", "component heterologous vaccine"], "article_id"=>1346188, "categories"=>["Biological Sciences"], "users"=>["Kelly L. Warfield", "John M. Dye", "Jay B. Wells", "Robert C. Unfer", "Frederick W. Holtsberg", "Sergey Shulenin", "Hong Vu", "Dana L. Swenson", "Sina Bavari", "M. Javad Aman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118881", "stats"=>{"downloads"=>12, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Homologous_and_Heterologous_Protection_of_Nonhuman_Primates_by_Ebola_and_Sudan_Virus_Like_Particles_/1346188", "title"=>"Homologous and Heterologous Protection of Nonhuman Primates by Ebola and Sudan Virus-Like Particles", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-03-20 04:47:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1965212"], "description"=>"<p><i>N</i>.<i>S</i>. = <i>no signs; N/A = not determined because the animal was deceased prior to the time point; fever was defined as a temperature more than 2</i>.<i>0°F over baseline; Temp drop was defined as a temperature more than 3</i>.<i>0°F below baseline; mild rash = focal areas of petechiae covering less than 10% of skin; moderate rash = areas of petechiae covering between 10% and 40% of the skin; severe rash = areas of petechiae or ecchymosis covering more than 40% of the skin</i></p><p><i>↑</i>, <i>2- to 3-fold increase</i></p><p><i>↑↑</i>, <i>4- to 5-fold increase</i></p><p><i>↑↑↑</i>, <i>> 5-fold increase</i></p><p><i>↓</i>, <i>2- to 3-fold decrease</i></p><p><i>WL</i>: <i>weight loss was the percentage compared to the weight at study initiation; BUN</i>: <i>blood urea nitrogen; ALT</i>: <i>alanine aminotransferase; AST</i>: <i>aspartate aminotransferase; ALP</i>: <i>alkaline phosphatase; ALB</i>: <i>albumin</i>, <i>Glu</i>: <i>glucose</i>, <i>Cre</i>: <i>creatinine</i>, <i>WBC</i>: <i>white blood cells; Plt</i>: <i>platelet</i>, <i>Lym</i>: <i>lymphocyte</i>.</p><p>Summary of the TAFV challenge study results through 15 days post challenge (study day 70–85).</p>", "links"=>[], "tags"=>["VP 40 matrix protein", "Several vaccine platforms", "TAFV", "EBOV nonhuman primate model", "protection", "RAVV", "infection", "SUDV", "Ta ï Forest virus", "MARV VLPs", "component heterologous vaccine"], "article_id"=>1346184, "categories"=>["Biological Sciences"], "users"=>["Kelly L. Warfield", "John M. Dye", "Jay B. Wells", "Robert C. Unfer", "Frederick W. Holtsberg", "Sergey Shulenin", "Hong Vu", "Dana L. Swenson", "Sina Bavari", "M. Javad Aman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118881.t003", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_TAFV_challenge_study_results_through_15_days_post_challenge_study_day_70_8211_85_/1346184", "title"=>"Summary of the TAFV challenge study results through 15 days post challenge (study day 70–85).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-03-20 04:47:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1965210"], "description"=>"<p>Macaques were vaccinated with 3 mg of SUDV VLPs (total protein content) along with 100ug of QS-21 at 0 and 6 weeks. Antibody responses were determined using an ELISA to detect IgGs against purified SUDV GPdTM or VP40 in sera drawn immediately prior to challenge. All six macaques were challenged with ∼1000 pfu of SUDV 4 weeks after the final vaccination (week 10).</p><p>SUDV VLP vaccine protects cynomolgus macaques from lethal infection with SUDV (Boniface isolate).</p>", "links"=>[], "tags"=>["VP 40 matrix protein", "Several vaccine platforms", "TAFV", "EBOV nonhuman primate model", "protection", "RAVV", "infection", "SUDV", "Ta ï Forest virus", "MARV VLPs", "component heterologous vaccine"], "article_id"=>1346182, "categories"=>["Biological Sciences"], "users"=>["Kelly L. Warfield", "John M. Dye", "Jay B. Wells", "Robert C. Unfer", "Frederick W. Holtsberg", "Sergey Shulenin", "Hong Vu", "Dana L. Swenson", "Sina Bavari", "M. Javad Aman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118881.t002", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SUDV_VLP_vaccine_protects_cynomolgus_macaques_from_lethal_infection_with_SUDV_Boniface_isolate_/1346182", "title"=>"SUDV VLP vaccine protects cynomolgus macaques from lethal infection with SUDV (Boniface isolate).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-03-20 04:47:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1965207"], "description"=>"<p>The data are shown as individual animal responses (circles) or as the mean antibody units for each group (lines) at each time point the samples were drawn. (A-D) Serum titers of VLP-vaccinated macaques were measured using the purified (A) SUDV GPdTM, (B) SUDV VP40, (C) EBOV GPdTM or (D) EBOV VP40 proteins using an IgG detection ELISA. (E) Antibody response to live virus in VLP-vaccinated animals prior to challenge. An ELISA was performed using live virus (EBOV, SUDV, TAFV, and Lassa virus) as the coating antigen. The data in Panels A-D represent empirically defined EC<sub>50</sub> values as described in Materials and Methods and data in Panel E are expressed as the means of the endpoint dilution (endpoint defined as inverse of last dilution with an OD > 0.2).</p>", "links"=>[], "tags"=>["VP 40 matrix protein", "Several vaccine platforms", "TAFV", "EBOV nonhuman primate model", "protection", "RAVV", "infection", "SUDV", "Ta ï Forest virus", "MARV VLPs", "component heterologous vaccine"], "article_id"=>1346179, "categories"=>["Biological Sciences"], "users"=>["Kelly L. Warfield", "John M. Dye", "Jay B. Wells", "Robert C. Unfer", "Frederick W. Holtsberg", "Sergey Shulenin", "Hong Vu", "Dana L. Swenson", "Sina Bavari", "M. Javad Aman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118881.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Humoral_responses_of_VLP_vaccinated_macaques_/1346179", "title"=>"Humoral responses of VLP-vaccinated macaques.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-20 04:47:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1965206"], "description"=>"<p>(A-B) Antibody titers from vaccinated animals were measured using the purified SUDV GPdTM (A) or VP40 (B) IgG ELISA. The data are expressed as the antibody units for each animal at each time point and the geometric mean for each group is shown by the lines, as indicated in the figure legends. (C) Infectious virus detectable in the sera of NHPs challenged with SUDV on study day 70 was determined using a standard plaque assay; data are represented as the values for individual monkeys. (D-F) Serum samples were collected at multiple time points during the challenge portion of the study and assayed for clinical chemistry/enzymatic levels including (D) alanine aminotransferase, (E) aspartate aminotransferase, and (F) blood urea nitrogen.</p>", "links"=>[], "tags"=>["VP 40 matrix protein", "Several vaccine platforms", "TAFV", "EBOV nonhuman primate model", "protection", "RAVV", "infection", "SUDV", "Ta ï Forest virus", "MARV VLPs", "component heterologous vaccine"], "article_id"=>1346178, "categories"=>["Biological Sciences"], "users"=>["Kelly L. Warfield", "John M. Dye", "Jay B. Wells", "Robert C. Unfer", "Frederick W. Holtsberg", "Sergey Shulenin", "Hong Vu", "Dana L. Swenson", "Sina Bavari", "M. Javad Aman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118881.g001", "stats"=>{"downloads"=>0, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serology_responses_following_SUDV_VLP_QS_21_SVLP_or_QS_21_only_Control_C_vaccination_and_clinical_laboratory_analysis_following_virus_challenge_/1346178", "title"=>"Serology responses following SUDV VLP + QS-21 (SVLP) or QS-21 only (Control, C) vaccination and clinical laboratory analysis following virus challenge.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-20 04:47:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1965209"], "description"=>"<p>Macaques were vaccinated with 3 mg of EBOV VLPs (total protein content) in 100ug of QS-21 at 6 week intervals with all challenges of ∼1000 pfu EBOV occurring 4 weeks after the final vaccination. Antibody responses were determined using an ELISA to detect IgGs against purified EBOV GPdTM or VP40 in sera drawn immediately prior to challenge.</p><p>Protection afforded by eVLP vaccines after 1 or 2 doses in cynomolgus macaques.</p>", "links"=>[], "tags"=>["VP 40 matrix protein", "Several vaccine platforms", "TAFV", "EBOV nonhuman primate model", "protection", "RAVV", "infection", "SUDV", "Ta ï Forest virus", "MARV VLPs", "component heterologous vaccine"], "article_id"=>1346181, "categories"=>["Biological Sciences"], "users"=>["Kelly L. Warfield", "John M. Dye", "Jay B. Wells", "Robert C. Unfer", "Frederick W. Holtsberg", "Sergey Shulenin", "Hong Vu", "Dana L. Swenson", "Sina Bavari", "M. Javad Aman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118881.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protection_afforded_by_eVLP_vaccines_after_1_or_2_doses_in_cynomolgus_macaques_/1346181", "title"=>"Protection afforded by eVLP vaccines after 1 or 2 doses in cynomolgus macaques.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-03-20 04:47:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1965208"], "description"=>"<p>Quantitation of virus infectivity was determined using a standard plaque assay and is represented as the values for individual monkeys on each study day after the challenge date (day 70).</p>", "links"=>[], "tags"=>["VP 40 matrix protein", "Several vaccine platforms", "TAFV", "EBOV nonhuman primate model", "protection", "RAVV", "infection", "SUDV", "Ta ï Forest virus", "MARV VLPs", "component heterologous vaccine"], "article_id"=>1346180, "categories"=>["Biological Sciences"], "users"=>["Kelly L. Warfield", "John M. Dye", "Jay B. Wells", "Robert C. Unfer", "Frederick W. Holtsberg", "Sergey Shulenin", "Hong Vu", "Dana L. Swenson", "Sina Bavari", "M. Javad Aman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118881.g003", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Infectious_virus_detectable_in_the_sera_of_NHPs_vaccinated_with_QS_21_adjuvant_and_EBOV_VLPs_A_SUDV_VLPs_B_EBOV_and_SUDV_VLPs_C_or_adjuvant_only_D_and_challenged_with_TAFV_on_study_day_70_/1346180", "title"=>"Infectious virus detectable in the sera of NHPs vaccinated with QS-21 adjuvant and EBOV VLPs (A), SUDV VLPs (B), EBOV and SUDV VLPs (C), or adjuvant only (D) and challenged with TAFV on study day 70.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-20 04:47:57"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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