{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:30:52Z","timestamp":1786645852305,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014617","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000}}],"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["408294\/2024-8"],"award-info":[{"award-number":["408294\/2024-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["407077\/2022-7"],"award-info":[{"award-number":["407077\/2022-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303044\/2020-9"],"award-info":[{"award-number":["303044\/2020-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2023\/02577-5"],"award-info":[{"award-number":["2023\/02577-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Schistosomiasis remains a major neglected tropical disease, and the development of a safe, effective vaccine is a global priority. Sm29, a\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    surface antigen associated with naturally acquired resistance, has emerged as a promising vaccine candidate; however, its translational advancement requires both high-quality antigen production and evaluation with clinically acceptable adjuvants. Here, we report a Good Laboratory Practice-aligned process for generating tag-free recombinant Sm29 in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , including multi-step anion-exchange chromatography followed by subsequent removal of residual impurities. Analytical validation demonstrated high purity, minimal host cell proteins and residual DNA and low endotoxin levels compliant with international regulatory standards. We then assessed the immunogenicity and protective efficacy of recombinant Sm29 formulated with alum or the squalene-based emulsion (CTVad1) in a murine model of\n                    <jats:italic>S. mansoni<\/jats:italic>\n                    infection. Both formulations elicited robust humoral immune responses, characterized by high titers of total IgG, IgG1, and IgG2c, and moderate levels of IgG3 and IgE anti-Sm29. Regarding cytokines, Sm29 formulated with alum induced a mixed Th1\/Th2 immunological profile while Sm29 adjuvanted with CTVad1 engendered a Th2-like response. Following cercarial challenge, CTVad1\u2009+\u2009Sm29 or Alum+Sm29 vaccinated mice displayed reduced worm burdens and liver pathology when compared to adjuvant controls. These findings demonstrate that a regulatory-compliant Sm29 antigen, combined with human-compatible adjuvants, induces robust immunity and protection against infection and supports further clinical advancement as a schistosomiasis vaccine candidate.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014617","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:45:22Z","timestamp":1786124722000},"page":"e0014617","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimization and production of a GLP-grade recombinant Sm29 vaccine against schistosomiasis: From expression to preclinical assessment"],"prefix":"10.1371","volume":"20","author":[{"given":"Juvana M.","family":"Andrade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio","family":"Mambelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharliton S.","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique F. 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response in mice previously exposed to a Schistosoma mansoni infection","volume":"9","author":"CC Alves","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"7198","key":"pntd.0014617.ref013","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nature06939","article-title":"Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants","volume":"453","author":"SC Eisenbarth","year":"2008","journal-title":"Nature"},{"issue":"1","key":"pntd.0014617.ref014","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4049\/jimmunol.181.1.17","article-title":"Cutting edge: inflammasome activation by alum and alum\u2019s adjuvant effect are mediated by NLRP3","volume":"181","author":"H Li","year":"2008","journal-title":"J Immunol"},{"key":"pntd.0014617.ref015","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.3389\/fimmu.2018.02488","article-title":"A strong humoral immune response induced by a vaccine formulation containing 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Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals. In: Services DoHH, editor. 1993."},{"key":"pntd.0014617.ref018","unstructured":"(EMA) EMA. ICH Q6B. Specifications: Test Procedures and Acceptance Criteria for Biotechnological\/Biological Products. In: Harmonisation ICf, editor. 1999."},{"key":"pntd.0014617.ref019","unstructured":"(EMA) EMA. ICH Q5E. Comparability of Biotechnological\/Biological Products. In: Harmonization ICf, editor. 2005."},{"key":"pntd.0014617.ref020","unstructured":"(EMA) EMA. Guideline on the Limits of Genotoxic Impurities. EMA. In: Use CfMPfH, editor. 2006."},{"key":"pntd.0014617.ref021","unstructured":"Brasil. ANVISA RDC 55\/2010: Registro de Produtos Biol\u00f3gicos. In: Sanit\u00e1ria ANdV, editor. 2010."},{"key":"pntd.0014617.ref022","unstructured":"(FDA) USFaDA. Guidance for Industry: Characterization and Qualification of Cell Substrates. 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