{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:09:12Z","timestamp":1791090552125,"version":"4.1.0"},"reference-count":45,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Schistosomiasis is a major parasitic disease affecting people living in tropical and sup-tropical areas. Transmission of the parasite has been reported in 78 countries, causing significant morbidity and around 200,000 deaths per year in endemic regions. The disease is currently managed by the mass-administration of praziquantel to populations at risk of infection; however, the reliance on a single drug raises the prospect of parasite resistance to the only treatment widely available. The development of an effective vaccine would be a more powerful method of control, but none currently exists and the identification of new immunogens that can elicit protective immune responses therefore remains a priority. Because of the complex nature of the parasite life cycle, identification of new vaccine candidates has mostly relied on the use of animal models and on a limited set of recombinant proteins.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    In this study, we have established an infrastructure for testing a large number of vaccine candidates in mice and used it to screen 96 cell-surface and secreted recombinant proteins from\n                    <ns4:italic>Schistosoma mansoni<\/ns4:italic>\n                    . This approach, using standardised immunisation and percutaneous infection protocols, allowed us to compare an extensive set of antigens in a systematic manner.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    Although some vaccine candidates were associated with a statistically significant reduction in the number of eggs in the initial screens, these observations could not be repeated in subsequent challenges and none of the proteins studied were associated with a strongly protective effect against infection.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    Although no antigens individually induced reproducible and strongly protective effects using our vaccination regime, we have established the experimental infrastructures to facilitate large-scale systematic subunit vaccine testing for schistosomiasis in a murine infection model.\n                  <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.15487.1","type":"journal-article","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T12:22:33Z","timestamp":1571228553000},"page":"159","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection"],"prefix":"10.12688","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0619-9797","authenticated-orcid":false,"given":"Cecile","family":"Crosnier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordelia","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7767-4922","authenticated-orcid":false,"given":"Gabriel","family":"Rinaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Clare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9581-0377","authenticated-orcid":false,"given":"Matt","family":"Berriman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0537-0863","authenticated-orcid":false,"given":"Gavin J.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2019,10,16]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"2253-64","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis.","volume":"383","author":"D Colley","year":"2014","journal-title":"Lancet."},{"key":"ref-2","first-page":"749-60","article-title":"Schistosomiasis and soil-transmitted helminthiases: number of people treated in 2016.","volume":"92","year":"2017","journal-title":"Wkly Epidemiol Rec."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"659-67","DOI":"10.1097\/QCO.0b013e328318978f","article-title":"Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis.","volume":"21","author":"M Doenhoff","year":"2008","journal-title":"Curr Opin Infect Dis."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1186\/s13071-016-1799-4","article-title":"Schistosomiasis vaccines: where do we stand?","volume":"9","author":"B Tebeje","year":"2016","journal-title":"Parasit Vectors."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"225-42","DOI":"10.1128\/CMR.00046-07","article-title":"Current status of vaccines for schistosomiasis.","volume":"21","author":"D McManus","year":"2008","journal-title":"Clin Microbiol Rev."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"2988-2991","DOI":"10.1016\/j.vaccine.2016.03.079","article-title":"Advancing a vaccine to prevent human schistosomiasis.","volume":"34","author":"M Merrifield","year":"2016","journal-title":"Vaccine."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"194-201","DOI":"10.1016\/j.pt.2016.10.010","article-title":"Sm-p80-Based Schistosomiasis Vaccine: Preparation for Human Clinical Trials.","volume":"33","author":"A Siddiqui","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"e0006968","DOI":"10.1371\/journal.pntd.0006968","article-title":"Safety and efficacy of the rSh28GST urinary schistosomiasis vaccine: A phase 3 randomized, controlled trial in Senegalese children.","volume":"12","author":"G Riveau","year":"2018","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"352-8","DOI":"10.1038\/nature08160","article-title":"The genome of the blood fluke Schistosoma mansoni.","volume":"460","author":"M Berriman","year":"2009","journal-title":"Nature."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"205-12","DOI":"10.1590\/s0074-02762006000900032","article-title":"Proteomic analysis of the schistosome tegument and its surface membranes.","volume":"101","author":"S Braschi","year":"2006","journal-title":"Mem Inst Oswaldo Cruz."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"347-56","DOI":"10.1074\/mcp.M500287-MCP200","article-title":"Proteins exposed at the adult schistosome surface revealed by biotinylation.","volume":"5","author":"S Braschi","year":"2006","journal-title":"Mol Cell Proteomics."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"e993","DOI":"10.1371\/journal.pntd.0000993","article-title":"Enzymatic shaving of the tegument surface of live schistosomes for proteomic analysis: a rational approach to select vaccine candidates.","volume":"5","author":"W Castro-Borges","year":"2011","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"e1455","DOI":"10.1371\/journal.pntd.0001455","article-title":"A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni.","volume":"6","author":"A Protasio","year":"2012","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"1178-94","DOI":"10.1017\/S0031182012000339","article-title":"Proteomics at the schistosome-mammalian host interface: any prospects for diagnostics or vaccines?","volume":"139","author":"R Wilson","year":"2012","journal-title":"Parasitology."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"123-35","DOI":"10.1007\/s00436-010-2045-1","article-title":"Screening the Schistosoma mansoni transcriptome for genes differentially expressed in the schistosomulum stage in search for vaccine candidates.","volume":"108","author":"L Farias","year":"2011","journal-title":"Parasitol Res."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"e1274","DOI":"10.1371\/journal.pntd.0001274","article-title":"Gene expression patterns in larval Schistosoma mansoni associated with infection of the mammalian host.","volume":"5","author":"S Parker-Manuel","year":"2011","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"201-11","DOI":"10.1016\/j.femsim.2005.03.009","article-title":"In vitro and in silico analysis of signal peptides from the human blood fluke, Schistosoma mansoni.","volume":"45","author":"M Pearson","year":"2005","journal-title":"FEMS Immunol Med Microbiol."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"e2091","DOI":"10.1371\/journal.pntd.0002091","article-title":"Comparative study of transcriptome profiles of mechanical- and skin-transformed Schistosoma mansoni schistosomula.","volume":"7","author":"A Protasio","year":"2013","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-19","first-page":"181-7","article-title":"Acquisition of human blood group antigens by Schistosoma mansoni.","volume":"26","author":"O Goldring","year":"1976","journal-title":"Clin Exp Immunol."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"483-94","DOI":"10.1098\/rspb.1969.0007","article-title":"Host antigens in schistosomiasis.","volume":"171","author":"S Smithers","year":"1969","journal-title":"Proc R Soc Lond B Biol Sci."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"918-921","DOI":"10.1016\/j.pt.2017.07.007","article-title":"Rethinking Schistosomiasis Vaccine Development: Synthetic Vesicles.","volume":"33","author":"M Egesa","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"341-65","DOI":"10.1016\/0014-4894(81)90122-3","article-title":"Schistosoma mansoni: ultrastructure of early transformation of skin- and shear-pressure-derived schistosomules.","volume":"51","author":"C Cousin","year":"1981","journal-title":"Exp Parasitol."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3389\/fimmu.2015.00085","article-title":"A Meta-Analysis of Experimental Studies of Attenuated Schistosoma mansoni Vaccines in the Mouse Model.","volume":"6","author":"M Fukushige","year":"2015","journal-title":"Front Immunol."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"e240","DOI":"10.1371\/journal.pntd.0000240","article-title":"Altered patterns of gene expression underlying the enhanced immunogenicity of radiation-attenuated schistosomes.","volume":"2","author":"G Dillon","year":"2008","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13071-016-1369-9","article-title":"Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?","volume":"9","author":"R Wilson","year":"2016","journal-title":"Parasit Vectors."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"835-40","DOI":"10.1038\/nm1430","article-title":"Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis.","volume":"12","author":"M Tran","year":"2006","journal-title":"Nat Med."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"e1564","DOI":"10.1371\/journal.pntd.0001564","article-title":"Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.","volume":"6","author":"M Pearson","year":"2012","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"593616","DOI":"10.1101\/593616","article-title":"A library of cell-surface and secreted proteins from Schistosoma mansoni identifies early serological markers of infection.","author":"C Crosnier","year":"2019","journal-title":"bioRxiv."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"622-30","DOI":"10.1101\/gr.7187808","article-title":"Large-scale screening for novel low-affinity extracellular protein interactions.","volume":"18","author":"K Bushell","year":"2008","journal-title":"Genome Res."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/1475-2875-13-93","article-title":"Towards a comprehensive Plasmodium falciparum merozoite cell surface and secreted recombinant protein library.","volume":"13","author":"Z Zenonos","year":"2014","journal-title":"Malar J."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"515-21","DOI":"10.1093\/protein\/7.4.515","article-title":"Expression of immunoglobulin and scavenger receptor superfamily domains as chimeric proteins with domains 3 and 4 of CD4 for ligand analysis.","volume":"7","author":"M Brown","year":"1994","journal-title":"Protein Eng."},{"key":"ref-32","article-title":"Data files describing the systemic screening of 96 Schistosoma mansoni cell surface and secreted antigens produced in a mammalian expression system.","author":"C Crosnier","year":"2019","journal-title":"figshare."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"3976-86","DOI":"10.1074\/mcp.O113.028357","article-title":"A library of functional recombinant cell-surface and secreted P. falciparum merozoite proteins.","volume":"12","author":"C Crosnier","year":"2013","journal-title":"Mol Cell Proteomics."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"Unit 19 1","DOI":"10.1002\/0471142735.im1901s103","article-title":"Schistosomiasis.","volume":"103","author":"M Tucker","year":"2013","journal-title":"Curr Protoc Immunol."},{"key":"ref-35","first-page":"328-31","article-title":"Conditions affecting the accuracy of potassium hydroxide digestion techniques for counting Schistosoma mansoni eggs in tissues.","volume":"39","author":"A Cheever","year":"1968","journal-title":"Bull World Health Organ."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"233-40","DOI":"10.1006\/expr.1997.4148","article-title":"Schistosoma mansoni: susceptibility differences between male and female mice can be mediated by testosterone during early infection.","volume":"85","author":"M Nakazawa","year":"1997","journal-title":"Exp Parasitol."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"460-6","DOI":"10.1097\/01.shk.0000142249.08135.e9","article-title":"Innate immune response in Th1- and Th2-dominant mouse strains.","volume":"22","author":"H Watanabe","year":"2004","journal-title":"Shock."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41541-018-0089-x","article-title":"Optimizing the utilization of aluminum adjuvants in vaccines: you might just get what you want.","volume":"3","author":"H HogenEsch","year":"2018","journal-title":"NPJ Vaccines."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"e308","DOI":"10.1371\/journal.pntd.0000308","article-title":"Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection.","volume":"2","author":"F Cardoso","year":"2008","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12879-016-1444-z","article-title":"A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis.","volume":"16","author":"A Ricciardi","year":"2016","journal-title":"BMC Infect Dis."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"38-51","DOI":"10.1111\/nyas.13942","article-title":"Sm-p80-based schistosomiasis vaccine: double-blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission-blocking efficacy.","volume":"1425","author":"W Zhang","year":"2018","journal-title":"Ann N Y Acad Sci."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"1-5","DOI":"10.1016\/j.coi.2013.12.007","article-title":"Immunomodulatory properties of the vaccine adjuvant alum.","volume":"28","author":"E Oleszycka","year":"2014","journal-title":"Curr Opin Immunol."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41541-018-0094-0","article-title":"Reprogramming the adjuvant properties of aluminum oxyhydroxide with nanoparticle technology.","volume":"4","author":"M Orr","year":"2019","journal-title":"NPJ Vaccines."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"949-954","DOI":"10.1038\/icb.2016.65","article-title":"IgG subclass co-expression brings harmony to the quartet model of murine IgG function.","volume":"94","author":"A Collins","year":"2016","journal-title":"Immunol Cell Biol."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"e2482","DOI":"10.1371\/journal.pntd.0002482","article-title":"On the three-finger protein domain fold and CD59-like proteins in Schistosoma mansoni.","volume":"7","author":"L Farias","year":"2013","journal-title":"PLoS Negl Trop Dis."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-159\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-159\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-159\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T06:40:11Z","timestamp":1590388811000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-159\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,16]]},"references-count":45,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.15487.1","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.16943.r36799","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16943.r36798","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16943.r36796","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16943.r36798","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16943.r36799","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16943.r36796","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,16]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-159\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.16943.r36796, Peter J. Hotez, Texas Children\u2019s Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA, 17 Oct 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-159\/v1#referee-response-36796","order":0,"name":"referee-response-36796","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16943.r36799, Henry J. McSorley, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK, 04 Nov 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-159\/v1#referee-response-36799","order":1,"name":"referee-response-36799","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16943.r36798, John P. Dalton, School of Biological Sciences, Queen's University Belfast, Belfast, UK, 13 Nov 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-159\/v1#referee-response-36798","order":2,"name":"referee-response-36798","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust (grant 206194). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}