Protection of Mice against Lethal Challenge with 2009 H1N1 Influenza A Virus by 1918-Like and Classical Swine H1N1 Based Vaccines
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{"title"=>"Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines", "type"=>"journal", "authors"=>[{"first_name"=>"Balaji", "last_name"=>"Manicassamy", "scopus_author_id"=>"6506285821"}, {"first_name"=>"Rafael A.", "last_name"=>"Medina", "scopus_author_id"=>"56384500300"}, {"first_name"=>"Rong", "last_name"=>"Hai", "scopus_author_id"=>"6603029779"}, {"first_name"=>"Tshidi", "last_name"=>"Tsibane", "scopus_author_id"=>"24559302400"}, {"first_name"=>"Silke", "last_name"=>"Stertz", "scopus_author_id"=>"6506346856"}, {"first_name"=>"Estanislao", "last_name"=>"Nistal-Villán", "scopus_author_id"=>"13005567800"}, {"first_name"=>"Peter", "last_name"=>"Palese", "scopus_author_id"=>"7005752957"}, {"first_name"=>"Christopher F.", "last_name"=>"Basler", "scopus_author_id"=>"6604022720"}, {"first_name"=>"Adolfo", "last_name"=>"García-Sastre", "scopus_author_id"=>"7006948562"}], "year"=>2010, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537366", "pui"=>"358387587", "doi"=>"10.1371/journal.ppat.1000745", "sgr"=>"77649216411", "scopus"=>"2-s2.0-77649216411", "isbn"=>"1553-7374 (Electronic)\\n1553-7366 (Linking)", "pmid"=>"20126449"}, "id"=>"86b8566c-1918-3926-8e0c-569999519f3c", "abstract"=>"The recent 2009 pandemic H1N1 virus infection in humans has resulted in nearly 5,000 deaths worldwide. Early epidemiological findings indicated a low level of infection in the older population (>65 years) with the pandemic virus, and a greater susceptibility in people younger than 35 years of age, a phenomenon correlated with the presence of cross-reactive immunity in the older population. It is unclear what virus(es) might be responsible for this apparent cross-protection against the 2009 pandemic H1N1 virus. We describe a mouse lethal challenge model for the 2009 pandemic H1N1 strain, used together with a panel of inactivated H1N1 virus vaccines and hemagglutinin (HA) monoclonal antibodies to dissect the possible humoral antigenic determinants of pre-existing immunity against this virus in the human population. By hemagglutinination inhibition (HI) assays and vaccination/challenge studies, we demonstrate that the 2009 pandemic H1N1 virus is antigenically similar to human H1N1 viruses that circulated from 1918-1943 and to classical swine H1N1 viruses. Antibodies elicited against 1918-like or classical swine H1N1 vaccines completely protect C57B/6 mice from lethal challenge with the influenza A/Netherlands/602/2009 virus isolate. In contrast, contemporary H1N1 vaccines afforded only partial protection. Passive immunization with cross-reactive monoclonal antibodies (mAbs) raised against either 1918 or A/California/04/2009 HA proteins offered full protection from death. Analysis of mAb antibody escape mutants, generated by selection of 2009 H1N1 virus with these mAbs, indicate that antigenic site Sa is one of the conserved cross-protective epitopes. Our findings in mice agree with serological data showing high prevalence of 2009 H1N1 cross-reactive antibodies only in the older population, indicating that prior infection with 1918-like viruses or vaccination against the 1976 swine H1N1 virus in the USA are likely to provide protection against the 2009 pandemic H1N1 virus. This data provides a mechanistic basis for the protection seen in the older population, and emphasizes a rationale for including vaccination of the younger, naive population. Our results also support the notion that pigs can act as an animal reservoir where influenza virus HAs become antigenically frozen for long periods of time, facilitating the generation of human pandemic viruses.", "link"=>"http://www.mendeley.com/research/protection-mice-against-lethal-challenge-2009-h1n1-influenza-virus-1918like-classical-swine-h1n1-bas", "reader_count"=>95, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>8, "Librarian"=>1, "Researcher"=>29, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>6, "Student > Master"=>4, "Student > Bachelor"=>11, "Lecturer"=>2, "Professor"=>7}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>8, "Librarian"=>1, "Researcher"=>29, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>6, "Student > Master"=>4, "Student > Bachelor"=>11, "Lecturer"=>2, "Professor"=>7}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>9, "Agricultural and Biological Sciences"=>55, "Medicine and Dentistry"=>12, "Business, Management and Accounting"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Psychology"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>13}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>13}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>55}, "Computer Science"=>{"Computer Science"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Vietnam"=>1, "United States"=>4, "Denmark"=>1, "Italy"=>1, "France"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/866096"], "description"=>"a<p>Range of HI antibody titer of 10 vaccinated mice per group.</p>b<p>HI titers represent the highest dilution that displayed hemagglutination inhibitory activity.</p>", "links"=>[], "tags"=>["mice", "sera", "homologous"], "article_id"=>536542, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.t001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HI_activity_of_mice_sera_against_homologous_virus_post_vaccination_/536542", "title"=>"HI activity of mice sera against homologous virus post-vaccination.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 02:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/865445"], "description"=>"<p>(A, B) Determination of LD<sub>50</sub> for the Neth/09 isolate in C57B/6 mice (n = 5/group). Mice were infected with the indicated doses of virus and their body weight (A) and survival (B) were monitored for 14 days. (C, D) Re-challenge of Cal/09 infected mice with Neth/09 (n = 4/group). Six weeks old C57B/6 mice were inoculated with PBS (Mock) or Cal/09 isolate (10<sup>3</sup> or 5×10<sup>4</sup> pfu). After 21 days the mice were challenged with 1×10<sup>6</sup> pfu of Neth/09 isolate. The body weight (C) and survival (D) were monitored for 14 days as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000745#ppat-1000745-g001\" target=\"_blank\">Fig. 1</a>.</p>", "links"=>[], "tags"=>["cross-protects", "mice", "lethal"], "article_id"=>535898, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Prior_infection_with_Cal_09_virus_cross_protects_mice_against_the_lethal_challenge_with_Neth_09_isolate_/535898", "title"=>"Prior infection with Cal/09 virus cross-protects mice against the lethal challenge with Neth/09 isolate.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:53:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/865769"], "description"=>"<p>Alignment of HA sequences from USSR/77, Tx/91, Bris/59/07 and 2009 human H1N1 viruses (top panel). Alignment of HA sequences from 1918, Sw/30, Wei/43, NJ/76 and 2009 H1N1 viruses (bottom panel). The antigenic sites are indicated in colored shaded boxes and were previously described by Brownlee and Fodor <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000745#ppat.1000745-Brownlee1\" target=\"_blank\">[42]</a>, using H3 numbering, as Cb (78–83), Sa (128–129, 156–160, 162–167), Sb (187–198), Ca1 (169–173, 206–208, 238–240) and Ca2 (140–145, 224–226).</p>", "links"=>[], "tags"=>["antigenic", "sites", "h1n1"], "article_id"=>536218, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.g005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_the_conservation_of_antigenic_sites_in_HA_of_H1N1_viruses_/536218", "title"=>"Comparison of the conservation of antigenic sites in HA of H1N1 viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:54:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/866140"], "description"=>"a<p>HI titers represent the highest dilution that displayed hemagglutination inhibitory activity.</p>b<p>Positive titers are bolded for clarity.</p>c<p>HI activity of sera from mice infected with Neth/09 is included for comparison.</p>d<p>Control- negative sera.</p>e<p>H3N2 strain representative used in the vaccination studies.</p>", "links"=>[], "tags"=>["polyclonal", "sera", "mice", "vaccinated", "h1n1"], "article_id"=>536583, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.t002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HI_activity_of_polyclonal_sera_from_mice_vaccinated_against_different_H1N1_isolates_/536583", "title"=>"HI activity of polyclonal sera from mice vaccinated against different H1N1 isolates.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 02:56:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/865371"], "description"=>"<p>(A) Body weight of BALB/c mice infected with the Cal/09 isolate. Six-week old BALB/c mice were infected with indicated dose of virus and body weights were monitored everyday as measure of virus induced disease. (B) Neth/09 isolate is more pathogenic than Cal/09 isolate in mice. C57B/6 mice were infected with either Cal/09 or Neth/602 isolate of 2009 pandemic H1N1 virus at indicated doses. (C) Comparison of survival rates of BALB/c and C57B/6 mice infected with Cal/04 and Neth/602 viruses. (D) Viral titers in the lungs of BALB/c mice infected with either 1×10<sup>3</sup> or 5×10<sup>4</sup> pfu of the Cal/09 isolate. (E) Viral titers in the lungs of C57B/6 mice infected with either 1×10<sup>3</sup> or 5×10<sup>4</sup> pfu of Cal/09 or 5×10<sup>4</sup> pfu of Neth/09. ND indicates that data was not determined. The body weights were measured everyday and are represented as a percentage of body weight prior to infection (n = 4 or 5 mice/group). Mice showing more than 25% of body weight loss were considered to have reached the experimental end point and were humanely euthanized. The lungs of 2–3 infected mice were excised and viral loads in the homogenates were measured by performing plaque assay in MDCK cells.</p>", "links"=>[], "tags"=>["pathogenicity", "2009", "pandemic", "h1n1", "isolates"], "article_id"=>535816, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.g001", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differences_in_pathogenicity_of_2009_pandemic_H1N1_virus_isolates_in_mice_/535816", "title"=>"Differences in pathogenicity of 2009 pandemic H1N1 virus isolates in mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:52:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/866187"], "description"=>"a<p>Specific HI activity of mAbs was calculated as the lowest concentration (µg/ml) of mAb that displayed hemagglutination inhibitory activity.</p>b<p>n/d: not determined.</p>", "links"=>[], "tags"=>["anti-ha", "monoclonal", "antibodies", "passive", "immunity"], "article_id"=>536638, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.t003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HI_activity_of_anti_HA_monoclonal_antibodies_used_for_passive_immunity_treatment_/536638", "title"=>"HI activity of anti-HA monoclonal antibodies used for passive immunity treatment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 02:57:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/865913"], "description"=>"<p>(A) Ribbon representation of an HA monomer (H1 and H2) of the three viruses. Individual antigenic sites are highlighted by green ellipses in the HA monomers. (B) Top panel: Zenithal surface top view of HA trimeric complexes depicting antigenic sites and their differences among 1918, Cal/09 and Bris/59/07 viruses. Blue color corresponds to conserved amino acids and red color represents amino acids that differ from 1918 HA. The antigenic sites are colored in light blue. Bottom panel: Close-up view of antigenic site Sa in monomeric 1918 and Cal/04 HAs. Amino acids K171, G172 and K180 (K157, G158 and K166 by H3 numbering) corresponding to mAb escape mutations are shown in yellow.</p>", "links"=>[], "tags"=>["antigenic", "differences", "structures"], "article_id"=>536368, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.g006", "stats"=>{"downloads"=>2, "page_views"=>60, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_antigenic_differences_in_the_HA_structures_of_1918_Cal_09_and_Bris_59_07_viruses_/536368", "title"=>"Comparison of antigenic differences in the HA structures of 1918, Cal/09 and Bris/59/07 viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:55:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/866056"], "description"=>"a<p>H3 numbering are shown in parenthesis.</p>", "links"=>[], "tags"=>["mab", "mutants"], "article_id"=>536509, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.t005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cross_reactive_mAb_escape_mutants_of_Cal_09_/536509", "title"=>"Cross-reactive mAb escape mutants of Cal/09.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 02:56:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/865674"], "description"=>"<p>Nine week old, C57B/6 mice were passively immunized with a total 150 µg of indicated monoclonal antibody (intraperitoneal route) 24 hr prior to viral challenge. After antibody administration, the mice were challenged with Neth/09 isolate at a dose 50 LD<sub>50</sub>. (A) Body weight of passively immunized mice challenged with Neth/09 (n = 5/group). (B) Survival of passively immunized mice post-challenge with Neth/09. (C) Viral Titers in the lungs at days 3 and 6 p.c. Viral load in the lungs homogenates were quantified as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000745#ppat-1000745-g001\" target=\"_blank\">Fig. 1</a>. Control (No Ab) mice are the same as controls in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000745#ppat-1000745-g003\" target=\"_blank\">Fig. 3</a> and are included for direct comparison.</p>", "links"=>[], "tags"=>["immunization", "mice", "1918", "2009", "h1n1", "cross-reactive", "antibodies", "protects"], "article_id"=>536114, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.g004", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Passive_immunization_of_mice_with_1918_and_2009_H1N1_HA_specific_cross_reactive_antibodies_protects_against_Neth_09_/536114", "title"=>"Passive immunization of mice with 1918 and 2009 H1N1 HA specific cross-reactive antibodies protects against Neth/09.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:54:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/865544"], "description"=>"<p>Five weeks old C57B/6 were immunized with 15 µg of the indicated inactivated viruses or with 1918 VLP vaccine followed by a boost (15 µg) after two weeks. Four weeks after the first immunization, vaccinated mice were challenged with Neth/09 isolate at a dose of 50 LD<sub>50</sub> (7.9×10<sup>5</sup> pfu). Mice were monitored for body weight loss and survival for 14 days as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000745#ppat-1000745-g001\" target=\"_blank\">Fig. 1</a>. (A) Body weight of classical swine H1N1 (Sw/30, NJ/76), 1918 VLP and human H1N1 Wei/43 vaccinated mice after challenge with Neth/09 (n = 4 or 5 mice/group) (D) Body weight of mice vaccinated with contemporary (from 1977–2007) H1N1 or H3N2 inactivated virus after challenge with Neth/09 (n = 4 or 5 mice/group). (B, E) Survival of mice vaccinated with H1N1 and H3N2 viruses post-challenge. (C, F) Viral titers in H1N1 and H3N2 vaccinated mice on days 3 and 6 p.c. Each data point represents the average viral titers from 2 or 3 mice. A single group of control (no vaccine) mice were used and are included in all the panels for direct comparison. The Cal/09 vaccinated group is also included on (A) and (B) for comparison.</p>", "links"=>[], "tags"=>["mice", "1943", "swine", "h1n1", "virus-based", "inactive", "vaccines", "protects", "lethal"], "article_id"=>535990, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccination_of_mice_with_1918_1943_and_classical_swine_H1N1_virus_based_inactive_vaccines_protects_against_Neth_09_lethal_infection_/535990", "title"=>"Vaccination of mice with 1918, 1943 and classical swine H1N1 virus-based inactive vaccines protects against Neth/09 lethal infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:53:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/866019"], "description"=>"a<p>HI titers represent the highest dilution that displayed hemagglutination inhibitory activity.</p>b<p>N/A: Not applicable, n/d: not determined.</p>", "links"=>[], "tags"=>["titers", "passively", "immunized", "mice"], "article_id"=>536466, "categories"=>["Virology", "Medicine", "Infectious Diseases"], "users"=>["Balaji Manicassamy", "Rafael A. Medina", "Rong Hai", "Tshidi Tsibane", "Silke Stertz", "Estanislao Nistal-Villán", "Peter Palese", "Christopher F. Basler", "Adolfo García-Sastre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1000745.t004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_HI_titers_in_passively_immunized_mice_pre_challenge_/536466", "title"=>"<i>In vivo</i> HI titers in passively immunized mice pre-challenge.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 02:56:15"}

PMC Usage Stats | Further Information

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Relative Metric

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