{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:42:15Z","timestamp":1792741335698,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011236","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000}}],"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN27220130015I"],"award-info":[{"award-number":["HHSN27220130015I"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN75N93021C00012"],"award-info":[{"award-number":["HHSN75N93021C00012"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Recombinant <jats:italic>Schistosoma mansoni<\/jats:italic> Tetraspanin-2 formulated on Alhydrogel (<jats:italic>Sm<\/jats:italic>-TSP-2\/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic>. The tegumentary <jats:italic>Sm<\/jats:italic>-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic> transmission in Brazil, and preclinical studies in which vaccination with <jats:italic>Sm<\/jats:italic>-TSP-2 protected mice following infection challenge.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic> transmission. In each cohort of 20 participants, 16 were randomized to receive one of two formulations of <jats:italic>Sm<\/jats:italic>-TSP-2 vaccine (adjuvanted with Alhydrogel only, or with Alhydrogel plus the Toll-like receptor-4 agonist, AP 10\u2013701), and 4 to receive Euvax B hepatitis B vaccine. Successively higher doses of antigen (10 \u03bcg, 30 \u03bcg, and 100 \u03bcg) were administered in a dose-escalation fashion, with progression to the next dose cohort being dependent upon evaluation of 7-day safety data after all participants in the preceding cohort had received their first dose of vaccine. Each participant received 3 intramuscular injections of study product at intervals of 2 months and was followed for 12 months after the third vaccination. IgG and IgG subclass antibody responses to <jats:italic>Sm<\/jats:italic>-TSP-2 were measured by qualified indirect ELISAs at pre- and post-vaccination time points through the final study visit.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p><jats:italic>Sm<\/jats:italic>-TSP-2\/Alhydrogel administered with or without AP 10-701 was well-tolerated in this population. The most common solicited adverse events were mild injection site tenderness and pain, and mild headache. No vaccine-related serious adverse events or adverse events of special interest were observed. Groups administered <jats:italic>Sm<\/jats:italic>-TSP-2\/Alhydrogel with AP 10\u2013701 had higher post-vaccination levels of antigen-specific IgG antibody. A significant dose-response relationship was seen in those administered <jats:italic>Sm<\/jats:italic>-TSP-2\/Alhydrogel with AP 10\u2013701. Peak anti-<jats:italic>Sm<\/jats:italic>-TSP-2 IgG levels were observed approximately 2 weeks following the third dose, regardless of <jats:italic>Sm<\/jats:italic>-TSP-2 formulation. IgG levels fell to low levels by Day 478 in all groups except the 100 \u03bcg with AP 10\u2013701 group, in which 57% of subjects (4 of 7) still had IgG levels that were \u22654-fold higher than baseline. IgG subclass levels mirrored those of total IgG, with IgG1 being the predominant subclass response.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Vaccination of adults with <jats:italic>Sm<\/jats:italic>-TSP-2\/Alhydrogel in an area of ongoing <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic> transmission was safe, minimally reactogenic, and elicited significant IgG and IgG subclass responses against the vaccine antigen. These promising results have led to initiation of a Phase 2 clinical trial of this vaccine in an endemic region of Uganda.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03110757\" xlink:type=\"simple\">NCT03110757<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011236","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T17:56:43Z","timestamp":1680199003000},"page":"e0011236","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic 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