Inconsistent Protective Efficacy and Marked Polymorphism Limits the Value of Schistosoma japonicum Tetraspanin-2 as a Vaccine Target
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{"title"=>"Inconsistent protective efficacy and marked polymorphism limits the value of Schistosoma japonicum tetraspanin-2 as a vaccine target", "type"=>"journal", "authors"=>[{"first_name"=>"Wenbao", "last_name"=>"Zhang", "scopus_author_id"=>"7409426686"}, {"first_name"=>"Jun", "last_name"=>"Li", "scopus_author_id"=>"27170851200"}, {"first_name"=>"Mary", "last_name"=>"Duke", "scopus_author_id"=>"8043938000"}, {"first_name"=>"Malcolm K.", "last_name"=>"Jones", "scopus_author_id"=>"7501846047"}, {"first_name"=>"Ling", "last_name"=>"Kuang", "scopus_author_id"=>"42761729200"}, {"first_name"=>"Jianfeng", "last_name"=>"Zhang", "scopus_author_id"=>"42762404600"}, {"first_name"=>"David", "last_name"=>"Blair", "scopus_author_id"=>"7202955592"}, {"first_name"=>"Yuesheng", "last_name"=>"Li", "scopus_author_id"=>"18335444000"}, {"first_name"=>"Donald P.", "last_name"=>"McManus", "scopus_author_id"=>"7102763765"}], "year"=>2011, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"issn"=>"19352727", "pui"=>"361887749", "doi"=>"10.1371/journal.pntd.0001166", "sgr"=>"79957975544", "scopus"=>"2-s2.0-79957975544", "isbn"=>"1935-2735 (Electronic)\\r1935-2727 (Linking)", "pmid"=>"21655308"}, "id"=>"b305f99d-63c5-3ca0-af2a-7da55cebedf6", "abstract"=>"BACKGROUND: Schistosoma mansoni tetraspanin 2 (Sm-TSP-2) has been shown to be strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection, but not chronically infected people, and to induce high levels of protection against challenge infection in the murine model of schistosomiasis. Amplification by PCR of homologous sequences from male and female S. japonicum worms showed the presence of 7 different clusters or subclasses of S. japonicum TSP-2. We determined the protective efficacy of one subclass - Sj-TSP-2e.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Following the alignment of 211 cDNAs, we identified 7 clusters encoding S. japonicum TSP-2 (Sj-TSP-2) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms. Quantitative PCR analysis revealed elevated expression of Sj-TSP-2 in adult worms compared with other life cycle stages. We expressed in E. coli the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients. Vaccination of mice with the recombinant protein induced high levels of IgG1 and IgG2 antibodies, but no consistent protective efficacy against challenge infection was elicited in three independent trials.\\n\\nCONCLUSIONS/SIGNIFICANCE: The highly polymorphic nature of the Sj-TSP-2 gene at the transcriptional level may limit the value of Sj-TSP-2 as a target for future S. japonicum vaccine development.", "link"=>"http://www.mendeley.com/research/inconsistent-protective-efficacy-marked-polymorphism-limits-value-schistosoma-japonicum-tetraspanin2", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>13, "Medicine and Dentistry"=>1, "Psychology"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>5}}, "reader_count_by_country"=>{"Brazil"=>1, "United Kingdom"=>1, "Australia"=>1, "India"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/386664", "https://ndownloader.figshare.com/files/386720"], "description"=>"<div><h3>Background</h3><p><em>Schistosoma mansoni</em> tetraspanin 2 (Sm-TSP-2) has been shown to be strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection, but not chronically infected people, and to induce high levels of protection against challenge infection in the murine model of schistosomiasis. Amplification by PCR of homologous sequences from male and female <em>S. japonicum</em> worms showed the presence of 7 different clusters or subclasses of <em>S. japonicum</em> TSP-2. We determined the protective efficacy of one subclass – Sj-TSP-2e.</p> <h3>Methodology/Principal Findings</h3><p>Following the alignment of 211 cDNAs, we identified 7 clusters encoding <em>S. japonicum</em> TSP-2 (<em>Sj-TSP-2</em>) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms. Quantitative PCR analysis revealed elevated expression of <em>Sj-TSP-2</em> in adult worms compared with other life cycle stages. We expressed in <em>E. coli</em> the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients. Vaccination of mice with the recombinant protein induced high levels of IgG1 and IgG2 antibodies, but no consistent protective efficacy against challenge infection was elicited in three independent trials.</p> <h3>Conclusions/Significance</h3><p>The highly polymorphic nature of the <em>Sj-TSP-2</em> gene at the transcriptional level may limit the value of Sj-TSP-2 as a target for future <em>S. japonicum</em> vaccine development.</p> </div>", "links"=>[], "tags"=>["inconsistent", "efficacy", "marked", "polymorphism", "limits", "tetraspanin-2"], "article_id"=>136321, "categories"=>["Cancer"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0001166.s001", "https://dx.doi.org/10.1371/journal.pntd.0001166.s002"], "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Inconsistent_Protective_Efficacy_and_Marked_Polymorphism_Limits_the_Value_of_Schistosoma_japonicum_Tetraspanin_2_as_a_Vaccine_Target/136321", "title"=>"Inconsistent Protective Efficacy and Marked Polymorphism Limits the Value of <em>Schistosoma japonicum</em> Tetraspanin-2 as a Vaccine Target", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-05-31 01:45:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/770913"], "description"=>"<p>Left panel, SDS-PAGE of soluble and insoluble proteins extracted from adult <i>S. japonicum</i> and recombinant proteins. Right panel: Recognition of recombinant Sj-TSP-2e and native proteins by antibodies in hyper immune mouse serum raised against recombinant Sj-TSP-2e. Lane M, protein markers; Lanes 1 and 2, soluble and insoluble proteins of <i>S. japonicum</i>; lane 3, Thi; lane 4, Sj-TSP-2e-Thi; lane 5, Sj-TSP-2e expressed in <i>Pichia</i> yeast; lane 6, Sm-TSP-2e-Thi; lane 7, Sj-23-GST-His as a control protein.</p>", "links"=>[], "tags"=>["recombinant"], "article_id"=>441281, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Purification_and_recognition_of_recombinant_Sj_TSP_2e_/441281", "title"=>"Purification and recognition of recombinant Sj-TSP-2e.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-31 00:21:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/770857"], "description"=>"<p>cDNAs were amplified with mRNA isolated from different stages of <i>S. japonicum</i> using specific primers designed from the conserved regions of Sj-TSP-2e. Ce, cercariae; So, schistosomula; Pw, paired adult worms; Ma, males; Fe, females. The bars (and *, X axis) show the fold changes compared with the cercarial stage. We used NADH-ubiquinone reductase as a house-keeping gene to calculate the number of copies of the gene expressed in each of the stages, and then converted these to fold changes by comparison with the number of copies in cercariae.</p>", "links"=>[], "tags"=>["levels", "sj-tsp-2e", "Real-time"], "article_id"=>441224, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_levels_of_Sj_TSP_2e_by_real_time_PCR_/441224", "title"=>"Expression levels of Sj-TSP-2e by real-time PCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-31 00:20:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/771145"], "description"=>"<p>Parasite sections were reacted with specific antibodies produced in mice against recombinant Sj-TSP-2e. The antibodies that specifically bound to the sections were probed with an anti-mouse IgG labelled with Cy3 conjugate (a, c). Red fluorescence in panel c indicates Sj-TSP-2e is located in the parasite tegument (teg); anti-thioredoxin (fusion protein tagged with 6His) antibodies in panel a did not react. DAPI to label nuclei (nuc in blue) (b, d) was used as a quality control marker for the sections. Tegument, teg.</p>", "links"=>[], "tags"=>["sj-tsp-2e"], "article_id"=>441513, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunolocalization_of_S_japonicum_Sj_TSP_2e_in_adult_female_worms_/441513", "title"=>"Immunolocalization of <i>S. japonicum</i> Sj-TSP-2e in adult female worms.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-31 00:25:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/770800"], "description"=>"<p>Protein sequences corresponding to the LEL region of Sj-TSP-2 encoded by 9 clusters of Sj-TSP-2 cDNAs were aligned with additional homologues found by BLAST searches in GenBank and others reported by Cai et al <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001166#pntd.0001166-Cai1\" target=\"_blank\">[8]</a>. Analysis was done as stated in the text. Clade credibility (posterior probability) values are shown at nodes. Protein sequence data reported in this paper are available in the GenBank, EMBL and DDBJ databases under the accession numbers ABR27733, AAX26611 and CAX70617.</p>", "links"=>[], "tags"=>["sj-tsp-2", "clusters"], "article_id"=>441165, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogenetic_analysis_of_Sj_TSP_2_clusters_with_homologues_/441165", "title"=>"Phylogenetic analysis of Sj-TSP-2 clusters with homologues.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-31 00:19:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/770650"], "description"=>"<p>The variable region is boxed. The large extracellular loop region is indicated by a solid line. Sj-TSP-2a (M8-1 and M6-1, GenBank accession numbers JF264973 and JF264974), Sj-TSP-2c (M2-11, JF264975), Sj-TSP-2d (M9-1, JF264977), Sj-TSP-2e (F2-2, JF264978), Sj-TSP-2f (F12-1, JF264982; F11-4, JF264983), Sj-TSP-2h (F11-7, JF264979; F11-9, JF264980; F3-1, JF264981) and Sj-TSP-2i (M2-1, JF264976) were from individual male (M) and female (F) worms. For instance, M8-1 represents number 8 male worm and number 1 clone.</p>", "links"=>[], "tags"=>["alignment", "tetraspanin"], "article_id"=>441009, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.g001", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protein_sequence_alignment_of_Schistosoma_japonicum_tetraspanin_2_Sj_TSP_2_isolated_from_adult_worms_/441009", "title"=>"Protein sequence alignment of <i>Schistosoma japonicum</i> tetraspanin 2 (Sj-TSP-2) isolated from adult worms.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-31 00:16:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/771321"], "description"=>"<p>Mouse serum anti-Sj-TSP-2e (fused with thioredoxin, Thi) antibodies were determined by ELISA after primary vaccination with <i>S. japonicum</i>-TSP-2e (Sj-TSP-2e) or <i>S. mansoni</i>-TSP-2 (Sm-TSP-2). Thioredoxin was used as control protein in the vaccine trials. The thin arrows indicate vaccination time points and the bold arrows indicate the time point of cercarial challenge.</p>", "links"=>[], "tags"=>["isotype", "levels", "mice", "challenged", "35"], "article_id"=>441687, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.g007", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antibody_isotype_levels_in_mice_challenged_with_35_S_japonicum_cercariae_/441687", "title"=>"Antibody isotype levels in mice challenged with 35 <i>S. japonicum</i> cercariae.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-31 00:28:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/771451"], "description"=>"<p>*, The variable region of the Sj-TSP-2 protein sequence from amino acid 155 to 158 of the full-length sequences.</p>†<p>, Two previously undescribed sequences;</p>‡<p>, same as Sj-TSP-2f in the variable region, which Cai et al. <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001166#pntd.0001166-Cai1\" target=\"_blank\">[8]</a> suggested was a different subclass as it contains substitutions in other regions.</p>", "links"=>[], "tags"=>["tetraspanin"], "article_id"=>441816, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Subclass_distribution_of_S_japonicum_tetraspanin_2_Sj_TSP_2_in_male_and_female_worms_/441816", "title"=>"Subclass distribution of <i>S. japonicum</i> tetraspanin 2 (Sj-TSP-2) in male and female worms.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-05-31 00:30:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/771487"], "description"=>"<p>Note: Thi, thioredoxin, as tag protein expressed in <i>E. coli</i> was used as a control protein. Sj-TSP2, Sj-TSP-2e; Sm-TSP2, Sm-TSP-2. Med, median; Redu, reduction = (1-number of median worms or eggs in experimental group/number of median worms or eggs in control group)×100%; ND, no data. HDC, high dose challenge with 35 cercariae; LDC, low dose challenge with 12 cercariae.</p>", "links"=>[], "tags"=>["mice", "vaccinated", "sjtsp-2e"], "article_id"=>441852, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.t002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccination_results_of_mice_vaccinated_with_SjTSP_2e_against_challenge_infection_with_Schistosoma_japonicum_cercariae_/441852", "title"=>"Vaccination results of mice vaccinated with SjTSP-2e against challenge infection with <i>Schistosoma japonicum</i> cercariae.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-05-31 00:30:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/771009"], "description"=>"<p>I: ELISA IgG screen of 72 sera collected from positive schistosomiasis japonica patients and 24 normal human sera (negative controls) probed by protein preparation from <i>S. japonicum</i> adult worms (SWAP), recombinant tag protein thioredoxin (Thio) and Sj-TSP-2e. II. Panel a: SDS-PAGE of soluble and insoluble protein extracted from adult <i>S. japonicum</i> and recombinant Sj-TSP-2e. Panels b and c: Western blot analysis with pooled sera randomly selected from confirmed schistosomiasis japonica patients (n = 15) and pooled sera from negative control subjects (n = 15) from northern China. Lane M, protein markers; lanes 1 and lane 2, soluble and insoluble proteins from adult <i>S. japonicum</i>; lane 3, Sj-TSP-2e (arrowed); lane 4, thioredoxin tag (Thi) (arrowed); lane 5, Sj-TSP-2e expressed in <i>Pichia</i> yeast (arrowed).</p>", "links"=>[], "tags"=>["recombinant", "sj-tsp-2e"], "article_id"=>441375, "categories"=>["Infectious Diseases"], "users"=>["Wenbao Zhang", "Jun Li", "Mary Duke", "Malcolm K. Jones", "Ling Kuang", "Jianfeng Zhang", "David Blair", "Yuesheng Li", "Donald P. McManus"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0001166.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Recognition_of_recombinant_Sj_TSP_2e_by_human_sera_/441375", "title"=>"Recognition of recombinant Sj-TSP-2e by human sera.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-31 00:22:55"}

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