{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:17:32Z","timestamp":1793506652899,"version":"4.5.0"},"reference-count":99,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T00:00:00Z","timestamp":1595548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1037304"],"award-info":[{"award-number":["APP1037304"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1117504"],"award-info":[{"award-number":["APP1117504"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host\u2013parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS\/MS of two types of extracellular vesicles (exosome-like, 120 k pellet vesicles and microvesicle-like, 15 k pellet vesicles) from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were identified in the 120 k pellet vesicles and larger 15 k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as Sm-TSP2, Sm23, glutathione S-transferase, saponins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (S. mansoni) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.<\/jats:p>","DOI":"10.3390\/vaccines8030416","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T11:16:35Z","timestamp":1595589395000},"page":"416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Schistosoma haematobium Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis"],"prefix":"10.3390","volume":"8","author":[{"given":"Gebeyaw G.","family":"Mekonnen","sequence":"first","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, Australia"},{"name":"Department of Medical Parasitology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bemnet A.","family":"Tedla","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Pickering","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Becker","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Hospital Center for Vaccine Development, Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6884-9452","authenticated-orcid":false,"given":"Bin","family":"Zhan","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Hospital Center for Vaccine Development, Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Bottazzi","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Hospital Center for Vaccine Development, Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1443-7233","authenticated-orcid":false,"given":"Javier","family":"Sotillo","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, Australia"},{"name":"Parasitology Reference and Research Laboratory, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0002-1544","authenticated-orcid":false,"given":"Mark S.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-018-0013-8","article-title":"Schistosomiasis","volume":"4","author":"McManus","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0001-706X(00)00122-4","article-title":"The global status of schistosomiasis and its control","volume":"77","author":"Chitsulo","year":"2000","journal-title":"Acta Trop."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S1473-3099(16)00175-4","article-title":"Outbreak of urogenital schistosomiasis in Corsica (France): An epidemiological case study","volume":"16","author":"Boissier","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","unstructured":"Berger, S. (2017). Schistosoma Haematobium, GIDEON Informatics Inc.. [2017 ed.]."},{"key":"ref_5","unstructured":"World Health Organization (2016). Schistosomiasis: Number of People Treated Worldwide in 2014. Weekly Epidemiol. Record, 91, 53\u201360."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.3201\/eid2009.140928","article-title":"schistosomiasis haematobium, Corsica, France","volume":"20","author":"Berry","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s00436-012-3151-z","article-title":"Susceptibility or resistance of praziquantel in human schistosomiasis: A review","volume":"111","author":"Wang","year":"2012","journal-title":"Parasitol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Vale, N., Gouveia, M.J., Rinaldi, G., Brindley, P.J., Gartner, F., and da Correia Costa, J.M. (2017). Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.02582-16"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/BF00389899","article-title":"Praziquantel, a new broad-spectrum antischistosomal agent","volume":"52","author":"Andrews","year":"1977","journal-title":"Z. Parasitenkunde"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00281-020-00789-x","article-title":"Schistosomiasis\u2014From immunopathology to vaccines","volume":"42","author":"McManus","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0169-4758(97)01198-8","article-title":"Why Don\u2019t We Have a Schistosomiasis Vaccine?","volume":"14","author":"Wilson","year":"1998","journal-title":"Parasitol. Today"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13071-016-1799-4","article-title":"Schistosomiasis vaccines: Where do we stand?","volume":"9","author":"Tebeje","year":"2016","journal-title":"Parasites Vectors"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Riveau, G., Schacht, A.-M., Dompnier, J.-P., Deplanque, D., Seck, M., Waucquier, N., Senghor, S., Delcroix-Genete, D., Hermann, E., and Idris-Khodja, N. (2018). Safety and efficacy of the rSh28GST urinary schistosomiasis vaccine: A phase 3 randomized, controlled trial in Senegalese children. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006968"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e12410","DOI":"10.1111\/pim.12410","article-title":"Parasite excretory-secretory products and their effects on metabolic syndrome","volume":"39","author":"Crowe","year":"2017","journal-title":"Parasite Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.molbiopara.2007.03.008","article-title":"Proteomic analysis of adult S","volume":"154","author":"Delcroix","year":"2007","journal-title":"mansoni gut contents. Mol. Biochem. Parasitol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.molbiopara.2011.05.002","article-title":"Insights into blood feeding by schistosomes from a proteomic analysis of worm vomitus","volume":"179","author":"Hall","year":"2011","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1074\/mcp.M800538-MCP200","article-title":"Excretory\/Secretory Proteome of the Adult Developmental Stage of Human Blood Fluke, Schistosoma japonicum","volume":"8","author":"Liu","year":"2009","journal-title":"Mol. Cell. Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sotillo, J., Pearson, M.S., Becker, L., Mekonnen, G.G., Amoah, A.S., Van Dam, G.J., Corstjens, P.L.A.M., Murray, J., Mduluza, T., and Mutapi, F. (2019). In-depth proteomic characterization of Schistosoma haematobium: Towards the development of new tools for elimination. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007362"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/imcb.12171","article-title":"Immunobiology of parasitic worm extracellular vesicles","volume":"96","author":"Eichenberger","year":"2018","journal-title":"Immunol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111264","DOI":"10.1016\/j.molbiopara.2020.111264","article-title":"Proteomic analysis of two populations of Schistosoma mansoni-derived extracellular vesicles: 15 k pellet and  120 k  pellet vesicles","volume":"236","author":"Kifle","year":"2020","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14760584.2018.1431125","article-title":"Extracellular vesicles from parasitic helminths and their potential utility as vaccines","volume":"17","author":"Mekonnen","year":"2018","journal-title":"Expert Rev. Vaccines"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1042\/ETLS20170095","article-title":"Extracellular vesicles as a target for the development of anti-helminth vaccines","volume":"1","author":"Kifle","year":"2017","journal-title":"Emerg. Top. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1413","DOI":"10.1002\/wrna.1413","article-title":"RNA in extracellular vesicles","volume":"8","author":"Kim","year":"2017","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D516","DOI":"10.1093\/nar\/gky1029","article-title":"Vesiclepedia 2019: A compendium of RNA, proteins, lipids and metabolites in extracellular vesicles","volume":"47","author":"Pathan","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.celrep.2017.05.001","article-title":"Extracellular vesicles from a helminth parasite suppress macrophage activation and constitute an effective vaccine for protective immunity","volume":"19","author":"Coakley","year":"2017","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.mib.2018.08.002","article-title":"Helminth extracellular vesicles in host-parasite interactions","volume":"46","author":"Tritten","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpara.2015.09.002","article-title":"Extracellular vesicles secreted by Schistosoma mansoni contain protein vaccine candidates","volume":"46","author":"Sotillo","year":"2016","journal-title":"Int. J. Parasitol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"28665","DOI":"10.3402\/jev.v4.28665","article-title":"Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni","volume":"4","author":"Nowacki","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1093\/infdis\/jiv291","article-title":"Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype","volume":"212","author":"Chaiyadet","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1074\/mcp.M115.053934","article-title":"The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis","volume":"14","author":"Cwiklinski","year":"2015","journal-title":"Mol. Cell. Proteom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25885","DOI":"10.1038\/srep25885","article-title":"Molecular characterization of S. japonicum exosome-like vesicles reveals their regulatory roles in parasite-host interactions","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.vetpar.2017.01.012","article-title":"Regulatory effects of Echinococcus multilocularis extracellular vesicles on RAW264.7 macrophages","volume":"235","author":"Zheng","year":"2017","journal-title":"Veter. Parasitol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nicolao, M.C., Rodrigues, C.R., and Cumino, A.C. (2019). Extracellular vesicles from Echinococcus granulosus larval stage: Isolation, characterization and uptake by dendritic cells. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007032"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"850","DOI":"10.3389\/fimmu.2018.00850","article-title":"Hookworm Secreted Extracellular Vesicles Interact With Host Cells and Prevent Inducible Colitis in Mice","volume":"9","author":"Eichenberger","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1428004","DOI":"10.1080\/20013078.2018.1428004","article-title":"Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host\u2013parasite communication","volume":"7","author":"Eichenberger","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jprot.2014.02.012","article-title":"Surface analysis of Dicrocoelium dendriticum. The molecular characterization of exosomes reveals the presence of miRNAs","volume":"105","author":"Bernal","year":"2014","journal-title":"J. Proteom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5488","DOI":"10.1038\/ncomms6488","article-title":"Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity","volume":"5","author":"Buck","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1578116","DOI":"10.1080\/20013078.2019.1578116","article-title":"Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite\u2013host cross talk","volume":"8","author":"Hansen","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s00436-015-4373-7","article-title":"Exosome-like vesicles derived by Schistosoma japonicum adult worms mediates M1 type immune-activity of macrophage","volume":"114","author":"Wang","year":"2015","journal-title":"Parasitol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zamanian, M., Fraser, L.M., Agbedanu, P.N., Harischandra, H., Moorhead, A.R., Day, T., Bartholomay, L.C., and Kimber, M.J. (2015). Release of Small RNA-containing Exosome-like Vesicles from the Human Filarial Parasite Brugia malayi. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004069"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e12536","DOI":"10.1111\/pim.12536","article-title":"Extracellular vesicles induce protective immunity against Trichuris muris","volume":"40","author":"Shears","year":"2018","journal-title":"Parasite Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chaiyadet, S., Sotillo, J., Krueajampa, W., Thongsen, S., Brindley, P.J., Sripa, B., Loukas, A., and Laha, T. (2019). Vaccination of hamsters with Opisthorchis viverrini extracellular vesicles and vesicle-derived recombinant tetraspanins induces antibodies that block vesicle uptake by cholangiocytes and reduce parasite burden after challenge infection. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007450"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.ijpara.2016.07.003","article-title":"Subcutaneous injection of exosomes reduces symptom severity and mortality induced by Echinostoma caproni infection in BALB\/c mice","volume":"46","author":"Trelis","year":"2016","journal-title":"Int. J. Parasitol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.pt.2015.06.009","article-title":"Exosomes and Other Extracellular Vesicles: The New Communicators in Parasite Infections","volume":"31","author":"Coakley","year":"2015","journal-title":"Trends Parasitol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0264-410X(01)00374-7","article-title":"Immunization with plasmid DNA encoding the integral membrane protein, Sm23, elicits a protective immune response against schistosome infection in mice","volume":"20","author":"Skelly","year":"2001","journal-title":"Vaccine"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Pearson, M.S., Pickering, D.A., McSorley, H.J., Bethony, J.M., Tribolet, L., Dougall, A.M., Hotez, P.J., and Loukas, A. (2012). Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001564"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nm1430","article-title":"Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis","volume":"12","author":"Tran","year":"2006","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6500","DOI":"10.1016\/j.vaccine.2019.08.075","article-title":"A phase 1 study of the safety, reactogenicity, and immunogenicity of a Schistosoma mansoni vaccine with or without glucopyranosyl lipid A aqueous formulation (GLA-AF) in healthy adults from a non-endemic area","volume":"37","author":"Keitel","year":"2019","journal-title":"Vaccine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.exppara.2010.05.018","article-title":"Schistosoma japonicum: Efficient and rapid purification of the tetraspanin extracellular loop 2, a potential protective antigen against schistosomiasis in mammalian","volume":"126","author":"Yuan","year":"2010","journal-title":"Exp. Parasitol."},{"key":"ref_50","unstructured":"Coico, R. (2013). Schistosomiasis. Current Protocols in Immunology, John Wiley and Sons, Inc."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Stroehlein, A.J., Korhonen, P.K., Chong, T.M., Lim, Y.L., Chan, K.-G., Webster, L.B., Rollinson, D., Brindley, P.J., Gasser, R., and Young, N.D. (2019). High-quality Schistosoma haematobium genome achieved by single-molecule and long-range sequencing. GigaScience, 8.","DOI":"10.1093\/gigascience\/giz108"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ng.1065","article-title":"Whole-genome sequence of Schistosoma haematobium","volume":"44","author":"Young","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1021\/pr049882h","article-title":"Open Source System for Analyzing, Validating, and Storing Protein Identification Data","volume":"3","author":"Craig","year":"2004","journal-title":"J. Proteome Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.1038\/ncomms6277","article-title":"MS-GF+ makes progress towards a universal database search tool for proteomics","volume":"5","author":"Kim","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1021\/pr101196n","article-title":"Faster SEQUEST Searching for Peptide Identification from Tandem Mass Spectra","volume":"10","author":"Diament","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/pmic.201000595","article-title":"SearchGUI: An open? Source graphical user interface for simultaneous OMSSA and X!Tandem searches","volume":"11","author":"Vaudel","year":"2011","journal-title":"Proteomics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"W29","DOI":"10.1093\/nar\/gkr367","article-title":"HMMER web server: Interactive sequence similarity searching","volume":"39","author":"Finn","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.1093\/bioinformatics\/bti610","article-title":"Blast2GO: A universal tool for annotation, visualization and analysis in functional genomics research","volume":"21","author":"Conesa","year":"2005","journal-title":"Bioinformation"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Supek, F., Bosnjak, M., Skunca, N., and \u0160muc, T. (2011). REVIGO Summarizes and Visualizes Long Lists of Gene Ontology Terms. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021800"},{"key":"ref_60","first-page":"175","article-title":"A hidden Markov model for predicting transmembrane helices in protein sequences","volume":"6","author":"Sonnhammer","year":"1998","journal-title":"Proc. Int. Conf. Intell. Syst. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/nmeth.1701","article-title":"SignalP 4.0: Discriminating signal peptides from transmembrane regions","volume":"8","author":"Petersen","year":"2011","journal-title":"Nat. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tedla, B.A., Pickering, D., Becker, L., Loukas, A., and Pearson, M.S. (2020). Vaccination with Schistosoma mansoni Cholinesterases Reduces the Parasite Burden and Egg Viability in a Mouse Model of Schistosomiasis. Vaccines, 8.","DOI":"10.1101\/2020.01.28.922732"},{"key":"ref_63","unstructured":"WHO (2019, January 20). Fact Sheet on Neglected Tropical Diseases. Available online: https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/schistosomiasis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40249-017-0286-2","article-title":"Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?","volume":"6","author":"Bergquist","year":"2017","journal-title":"Infect. Dis. Poverty"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1097\/00001432-200012000-00014","article-title":"Praziquantel: Is there real resistance and are there alternatives?","volume":"13","author":"Cioli","year":"2000","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3389\/fimmu.2018.00534","article-title":"Extracellular Vesicle Subtypes Released From Activated or Apoptotic T-Lymphocytes Carry a Specific and Stimulus-Dependent Protein Cargo","volume":"9","author":"Tucher","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/nrm3741","article-title":"Regulated protein turnover: Snapshots of the proteasome in action","volume":"15","author":"Bhattacharyya","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1007\/s00436-015-4360-z","article-title":"Proteasome stress responses in Schistosoma mansoni","volume":"114","author":"Ornelas","year":"2015","journal-title":"Parasitol. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.exppara.2005.01.002","article-title":"Schistosoma mansoni: Functional proteasomes are required for development in the vertebrate host","volume":"109","author":"Evangelista","year":"2005","journal-title":"Exp. Parasitol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.exppara.2007.08.002","article-title":"The 26S proteasome in Schistosoma mansoni: Bioinformatics analysis, developmental expression, and RNA interference (RNAi) studies","volume":"117","author":"Nabhan","year":"2007","journal-title":"Exp. Parasitol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/iub.1621","article-title":"Ferritin, cellular iron storage and regulation","volume":"69","author":"Arosio","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1042\/bj3570241","article-title":"Ferritin and the response to oxidative stress","volume":"357","author":"Orino","year":"2001","journal-title":"Biochem. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1016\/j.biocel.2007.04.017","article-title":"Tracking the fate of iron in early development of human blood flukes","volume":"39","author":"Jones","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_74","first-page":"129","article-title":"Mucosal immunization of recombinant Schistosoma japonicum ferritin","volume":"22","author":"Chen","year":"2004","journal-title":"Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/978-0-387-78267-6_5","article-title":"Calcium regulation and signaling in apicomplexan parasites","volume":"47","author":"Nagamune","year":"2008","journal-title":"Subcell. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15383","DOI":"10.1021\/bi9805238","article-title":"Calcium Induces Phospholipid Redistribution and Microvesicle Release in Human Erythrocyte Membranes by Independent Pathways\u2020","volume":"37","author":"Bucki","year":"1998","journal-title":"Biochemistry"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Sotillo, J., Robinson, M.W., Kimber, M.J., Cucher, M., Ancarola, M.E., Nejsum, P., Marcilla, A., Eichenberger, R.M., and Tritten, L. (2020). The protein and microRNA cargo of extracellular vesicles from parasitic helminths\u2014Current status and research priorities. Int. J. Parasitol.","DOI":"10.1016\/j.ijpara.2020.04.010"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.tcb.2004.09.014","article-title":"Renewing the conspiracy theory debate: Does Raf function alone to mediate Ras oncogenesis?","volume":"14","author":"Repasky","year":"2004","journal-title":"Trends Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10571-016-0366-z","article-title":"Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake","volume":"36","author":"Abels","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1017\/S003118209700173X","article-title":"Identification of Ras, MAP kinases, and a GAP protein in Schistosoma mansoni by immunoblotting and their putative involvement in male\u2013female interaction","volume":"115","author":"Grevelding","year":"1997","journal-title":"Parasitology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/jmr.654","article-title":"The substrate recognition mechanisms in chaperonins","volume":"17","author":"Carrascosa","year":"2004","journal-title":"J. Mol. Recognit."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4767","DOI":"10.1002\/j.1460-2075.1992.tb05582.x","article-title":"Function in protein folding of TRiC, a cytosolic ring complex containing TCP-1 and structurally related subunits","volume":"11","author":"Frydman","year":"1992","journal-title":"EMBO J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3389\/fimmu.2014.00442","article-title":"Tetraspanins in Extracellular Vesicle Formation and Function","volume":"5","author":"Andreu","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"14342","DOI":"10.1038\/s41598-017-13527-5","article-title":"Suppression of mRNAs encoding CD63 family tetraspanins from the carcinogenic liver fluke Opisthorchis viverrini results in distinct tegument phenotypes","volume":"7","author":"Chaiyadet","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Piratae, S., Tesana, S., Jones, M.K., Brindley, P.J., Loukas, A., Lovas, E., Eursitthichai, V., Sripa, B., Thanasuwan, S., and Laha, T. (2012). Molecular Characterization of a Tetraspanin from the Human Liver Fluke, Opisthorchis viverrini. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001939"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Tran, M.H., Freitas, T.C., Cooper, L., Gaze, S., Gatton, M., Jones, M.K., Lovas, E., Pearce, E.J., and Loukas, A. (2010). Suppression of mRNAs Encoding Tegument Tetraspanins from Schistosoma mansoni Results in Impaired Tegument Turnover. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000840"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Zhang, W., Li, J., Duke, M., Jones, M.K., Kuang, L., Zhang, J., Blair, D., Li, Y., and McManus, D.P. (2011). Inconsistent Protective Efficacy and Marked Polymorphism Limits the Value of Schistosoma japonicum Tetraspanin-2 as a Vaccine Target. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001166"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Kifle, D.W., Chaiyadet, S., Waardenberg, A.J., Wise, I., Cooper, M., Becker, L., Doolan, D.L., Laha, T., Sotillo, J., and Pearson, M.S. (2020). Uptake of Schistosoma mansoni extracellular vesicles by human endothelial and monocytic cell lines and impact on vascular endothelial cell gene expression. Int. J. Parasitol.","DOI":"10.1016\/j.ijpara.2020.05.005"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1365-3024.2009.01098.x","article-title":"Immunopathogenesis of human schistosomiasis","volume":"31","author":"Burke","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.trsl.2013.03.006","article-title":"New vaccines for neglected parasitic diseases and dengue","volume":"162","author":"Beaumier","year":"2013","journal-title":"Transl. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1365-3024.1993.tb00623.x","article-title":"Suppression of Schistosoma bovis egg production in cattle by vaccination with either glutathione S-transferase or keyhole limpet haemocyanin","volume":"15","author":"Bushara","year":"1993","journal-title":"Parasite Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.parint.2015.01.005","article-title":"Immunogenicity and anti-fecundity effect of nanoparticle coated glutathione S-transferase (SjGST) DNA vaccine against murine Schistosoma japonicum infection","volume":"64","author":"Mbanefo","year":"2015","journal-title":"Parasitol. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"442","DOI":"10.4269\/ajtmh.1980.29.442","article-title":"Observations on cattle schistosomiasis in the Sudan, a study in comparative medicine. II. Experimental demonstration of naturally acquired resistance to Schistosoma bovis","volume":"29","author":"Bushara","year":"1980","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0034-5288(18)32782-6","article-title":"Schistosoma bovis in calves: The development and clinical pathology of primary infections","volume":"28","author":"Saad","year":"1980","journal-title":"Res. Veter. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1017\/S0022149X00023853","article-title":"Parasitological and Pathological Observations on Schistosoma bovis Sonsion, 1876, in Calves, Sheep and Goats in Iran","volume":"47","author":"Massoud","year":"1973","journal-title":"J. Helminthol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/00034983.1969.11686603","article-title":"Schistosoma mansoni infection in rhesus monkeys: Changes in egg production and egg distribution in prolonged infections in intact and splenectomized monkeys","volume":"63","author":"Cheever","year":"1969","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/00034983.1976.11687140","article-title":"Acquired resistance to Schistosoma haematobium in the baboon (Papio anubis) after cercarial exposure and adult worm transplantation","volume":"70","author":"Webbe","year":"1976","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_98","unstructured":"WHO (2020, July 02). Ending the Neglect to Attain the Sustainable Development Goals: A Roadmap for Neglected Tropical Diseases 2021\u20132030. Available online: https:\/\/www.who.int\/neglected_diseases\/Ending-the-neglect-to-attain-the-SDGs--NTD-Roadmap.pdf?ua=1."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kura, K., Truscott, J.E., Toor, J., and Anderson, R.M. (2019). Modelling the impact of a Schistosoma mansoni vaccine and mass drug administration to achieve morbidity control and transmission elimination. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007349"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/3\/416\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:51:33Z","timestamp":1760176293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/3\/416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,24]]},"references-count":99,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["vaccines8030416"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8030416","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.24.168773","asserted-by":"object"}]},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,24]]}}}