Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans
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{"title"=>"Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans", "type"=>"journal", "authors"=>[{"first_name"=>"Robert B.", "last_name"=>"Couch", "scopus_author_id"=>"7102611225"}, {"first_name"=>"William K.", "last_name"=>"Decker", "scopus_author_id"=>"34973936500"}, {"first_name"=>"Budi", "last_name"=>"Utama", "scopus_author_id"=>"6506510856"}, {"first_name"=>"Robert L.", "last_name"=>"Atmar", "scopus_author_id"=>"7005296248"}, {"first_name"=>"Diane", "last_name"=>"Niño", "scopus_author_id"=>"16936323000"}, {"first_name"=>"Jing Qi", "last_name"=>"Feng", "scopus_author_id"=>"8351056000"}, {"first_name"=>"Matthew M.", "last_name"=>"Halpert", "scopus_author_id"=>"55524022100"}, {"first_name"=>"Gillian M.", "last_name"=>"Air", "scopus_author_id"=>"7005747759"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"366273697", "sgr"=>"84871147732", "issn"=>"19326203", "pmid"=>"23239987", "scopus"=>"2-s2.0-84871147732", "doi"=>"10.1371/journal.pone.0050830", "isbn"=>"1932-6203 (Electronic); 1932-6203 (Linking)"}, "id"=>"af3f600e-a8be-3d07-a39e-a8e10e022795", "abstract"=>"BACKGROUND: Serum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses.\\n\\nDESIGN: To help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM).\\n\\nRESULTS: Antigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were <1:4 for the H7 vaccine and 1:661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1) vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2) vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1) vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7) vaccine contained mostly small 5 to 20 nm structures.\\n\\nSUMMARY: Antigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.", "link"=>"http://www.mendeley.com/research/evaluations-vitro-correlates-immunogenicity-inactivated-influenza-h5-h7-h9-vaccines-humans", "reader_count"=>27, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>7, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>1, "Student > Doctoral Student"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>7, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>1, "Student > Doctoral Student"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>3, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>9, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Psychology"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>2, "United States"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/526858"], "description"=>"<p>Evaluation sequence of antigen uptake, processing and presentation of influenza A vaccine and HA antigens to human T cells.</p>", "links"=>[], "tags"=>["antigen", "influenza", "antigens"], "article_id"=>197342, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_sequence_of_antigen_uptake_processing_and_presentation_of_influenza_A_vaccine_and_HA_antigens_to_human_T_cells_/197342", "title"=>"Evaluation sequence of antigen uptake, processing and presentation of influenza A vaccine and HA antigens to human T cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:50:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/527578"], "description"=>"1<p>Scale of 0 to 4; 0 = none seen, 4 = abundant; <1 = rare.</p>", "links"=>[], "tags"=>["proportions", "morphologic", "units", "seen", "electron", "micrographs", "monovalent", "influenza"], "article_id"=>198060, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.t004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relative_Proportions_of_Different_Morphologic_Units_Seen_in_Electron_Micrographs_of_Monovalent_Influenza_Vaccines_/198060", "title"=>"Relative Proportions of Different Morphologic Units Seen in Electron Micrographs of Monovalent Influenza Vaccines.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 18:54:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/526959"], "description"=>"<p>Data are before and after dialysis with 10 and 20% of the initial vaccine or HA amount used so as to reduce any inhibitory effect. The vaccine concentration should not affect maturation; maturation in the presence of vaccine should be similar to the PBS control. The PBS control is also before and after dialysis. Available vaccine was insufficient for testing all four variables for the HA of Hong Kong/G1/99 (H9N2).</p>", "links"=>[], "tags"=>["dendritic", "cells", "maturing", "influenza", "antigen"], "article_id"=>197443, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percent_of_human_dendritic_cells_maturing_after_influenza_A_antigen_loading_/197443", "title"=>"Percent of human dendritic cells maturing after influenza A antigen loading.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:51:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/527245"], "description"=>"<p>Coomassie blue stain was used for protein and western blots with polyclonal antisera for protein identity. Gels are for vaccines (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-g004\" target=\"_blank\">Figure 4A</a>) and viruses (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-g004\" target=\"_blank\">Figure 4B</a>). Baculovirus expressed H3 HA was used as control (not shown).</p>", "links"=>[], "tags"=>["gels", "reducing", "nonreducing", "conditions", "trimeric", "ha1", "ha2", "subunits", "bound"], "article_id"=>197725, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Polyacrylamide_gels_run_under_reducing_and_nonreducing_conditions_for_trimeric_HA_and_HA1_and_HA2_subunits_bound_and_separate_/197725", "title"=>"Polyacrylamide gels run under reducing and nonreducing conditions for trimeric HA and HA1 and HA2 subunits bound and separate.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:52:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/527081"], "description"=>"<p>The viruses and vaccines were diluted to equivalent hemagglutination units (HAU) although not comparable for detergent-released HA in vaccines versus virus particles and the H7 vaccine had no HAU. Analysis of the binding curves gives total binding sites (Bmax) (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-g003\" target=\"_blank\">Figure 3A</a>) and overall avidity (Kd) (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-g003\" target=\"_blank\">Figure 3B</a>).</p>", "links"=>[], "tags"=>["unfoldon", "elisa", "assays", "viruses", "vaccines", "polyclonal", "antisera", "monoclonal"], "article_id"=>197559, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Native_and_unfoldon_ELISA_assays_for_viruses_and_vaccines_using_polyclonal_antisera_and_monoclonal_antibodies_/197559", "title"=>"Native and unfoldon ELISA assays for viruses and vaccines using polyclonal antisera and monoclonal antibodies.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:51:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/527427"], "description"=>"<p><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-g005\" target=\"_blank\">Figure 5A</a> shows intact and split virus particles (asterisks) in the influenza A/Cal/04 (H1N1) subunit vaccine (CSL) of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-t001\" target=\"_blank\">Table 1</a> along with structures of indistinct morphology (arrows). Also shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-g005\" target=\"_blank\">Figure 5A</a> is an EM of the A/Vietnam/04 (H5N1) subunit vaccine (SP) of references 5, 6, 10 in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-t001\" target=\"_blank\">Table 1</a> that was selected to show a large number of stellate structures (arrows point to examples) although indistinct structures similar to those in the H1N1 vaccine were dominant in the H5N1 vaccine (not shown). <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-g005\" target=\"_blank\">Figure 5B</a> is an EM of the influenza A/CK/G9 (H9N2) vaccine (Novartis) of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-t001\" target=\"_blank\">Table 1</a> that shows the predominant varying size particles of membrane with external projections as well as a number of stellates, one apparently within an empty particle (arrow). Also in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-g005\" target=\"_blank\">Figure 5B</a> is an EM of the influenza A/Mallard (H7N7) vaccine (SP, ref. 12 in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone-0050830-t001\" target=\"_blank\">Table 1</a>) that primarily showed small (5 to 20 nm) round and elongated structures (arrows point to examples). Some stellates and a rare intact particle were also seen.</p>", "links"=>[], "tags"=>["electron", "micrographs", "vaccines", "illustrating", "morphologic", "structures"], "article_id"=>197912, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.g005", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selected_electron_micrographs_of_vaccines_illustrating_the_morphologic_structures_described_in_Table_4_/197912", "title"=>"Selected electron micrographs of vaccines illustrating the morphologic structures described in <b>Table 4</b>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 18:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/527718"], "description"=>"1<p>Concentrations in single radial immunodiffusion (SRID) assays as reported to NIAID.</p>2<p>Mean of three tests.</p>3<p>Mean of two tests performed as recommended by Stevenson, et al. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050830#pone.0050830-Feng1\" target=\"_blank\">[43]</a>.</p>", "links"=>[], "tags"=>["titers", "monovalent", "inactivated", "influenza", "avian", "pandemic", "2009"], "article_id"=>198198, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.t003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hemagglutination_Titers_of_Monovalent_Inactivated_Influenza_A_Avian_and_Pandemic_2009_Influenza_A_Vaccines_/198198", "title"=>"Hemagglutination Titers of Monovalent Inactivated Influenza A Avian and Pandemic 2009 Influenza A Vaccines.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 18:54:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/527669"], "description"=>"1<p>Immature dendritic cells loaded with antigen, matured with cytokines and used to present antigens to T cells that secrete cytokines.</p>2<p>Monovalent vaccine (manufacturer) or recombinant HA proteins described in M&M.</p>3<p>As determined in FACS for CD83 and HLADR.</p>4<p>Numbers of ELISpots for indicated cytokine secretion after T cell stimulation; unstimulated lymphocytes, DC only and medium controls did not show ELISpots.</p>5<p>The test was before and after dialysis in a repeat test, after dialysis result shown.</p>6<p>NT = not tested.</p>", "links"=>[], "tags"=>["maturation", "cytokine", "secretion", "cells", "stimulated", "vitro", "influenza", "vaccines", "hemagglutinin"], "article_id"=>198148, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dendritic_Cell_Maturation_and_Cytokine_Secretion_by_T_Cells_Stimulated_in_vitro_with_Influenza_A_Virus_Vaccines_and_Hemagglutinin_Proteins_1_/198148", "title"=>"Dendritic Cell Maturation and Cytokine Secretion by T Cells Stimulated in vitro with Influenza A Virus Vaccines and Hemagglutinin Proteins.<sup>1</sup>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 18:54:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/527628"], "description"=>"1<p>All are after two doses of subunit vaccine 3–4 weeks apart and all trials were in healthy adults aged 18 to 49 except as noted.</p>2<p>Vaccine subtype and strain.</p>3<p>Manufacturer: SP – Sanofi Pasteur; GSK – GlaxoSmithKline, Wyeth – batch donated to NIAID.</p>4<p>Percents are for clinical trials reporting results for the dosages listed. Dosages are as determined in single radial immunodiffusion assays (SRID).</p>5<p>Data are FDA reanalysis of trial results reported in reference 2.</p>6<p>Data provided by Belshe, RB, et al. (ref 10).</p>7<p>Data are after one dose for ages 18–64 and 18–49 and after two doses for 3–9 and 0.5–3.</p>8<p>Clinical trial results for vaccines used in this study, references 5, 6, 10 were with the USA licensed H5/VN/04 vaccine.</p>", "links"=>[], "tags"=>["subjects", "serum", "hemagglutination-inhibition", "antibody", "titers", "dosage", "vaccinations", "monovalent", "inactivated", "influenza"], "article_id"=>198104, "categories"=>["Biotechnology", "Virology", "Infectious Diseases", "Immunology"], "users"=>["Robert B. Couch", "William K. Decker", "Budi Utama", "Robert L. Atmar", "Diane Niño", "Jing Qi Feng", "Matthew M. Halpert", "Gillian M. Air"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050830.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentage_of_Subjects_Developing_Serum_Hemagglutination_inhibition_Antibody_Titers_1_40_or_1_32_by_Vaccine_HA_Dosage_after_Vaccinations_with_Monovalent_Inactivated_Influenza_A_Virus_Vaccines_1_/198104", "title"=>"Percentage of Subjects Developing Serum Hemagglutination-inhibition Antibody Titers ≥1∶40 (or 1∶32) by Vaccine HA Dosage after Vaccinations with Monovalent Inactivated Influenza A Virus Vaccines.<sup>1</sup>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 18:54:22"}

PMC Usage Stats | Further Information

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Relative Metric

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