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Parasite\u2019s EVs manipulate the immune system, making them probable next-generation vaccines. Schistosomal EVs carry different proteins of promising immunizing potentials. For evaluating the immune-protective role of<jats:italic>Schistosoma mansoni<\/jats:italic>(<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>) egg-derived EVs against murine schistosomiasis, EVs were isolated from cultured<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>eggs by progressive sequential cooling ultra-centrifugation technique. Isolated EVs were structurally identified using transmission electron microscope and their protein was quantified by Lowry\u2019s technique. Experimental mice were subcutaneously immunized with three doses of 20 \u03bcg EVs (with or without alum adjuvant); every two weeks, then were challenged with<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>cercariae two weeks after the last immunizing dose. Six weeks post infection, mice were sacrificed for vaccine candidate assessment. EVs protective efficacy was evaluated through parasitological, histopathological, and immunological parameters. Results showed significant reduction of tegumentally deranged adult worms, hepatic and intestinal egg counts reduction by 46.58%, 93.14% and 93.17% respectively, accompanied by remarkable amelioration of sizes, numbers and histopathology of hepatic granulomata mediated by high interferon gamma (IFN \u03b3) and antibody level. Using sera from vaccinated mice, the molecular weight of EVs\u2019 protein components targeted by the antibody produced was recognized by western immunoblot. Results revealed two bands of ~ 14 KDa and ~ 21 KDa, proving that EVs are able to stimulate specific antibodies response. In conclusion, the present study highlighted the role of<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>-egg derived EVs as a potential vaccine candidate against murine schistosomiasis mansoni.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009866","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T19:07:31Z","timestamp":1634152051000},"page":"e0009866","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Schistosoma mansoni egg-derived extracellular vesicles: A promising vaccine candidate against murine schistosomiasis"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-4067","authenticated-orcid":true,"given":"Shereen F.","family":"Mossallam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1095-7263","authenticated-orcid":true,"given":"Iman F.","family":"Abou-El-Naga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany","family":"Abdel Bary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman A.","family":"Elmorsy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6466-3450","authenticated-orcid":true,"given":"Radwa G.","family":"Diab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"pntd.0009866.ref001","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.curtheres.2019.06.001","article-title":"Schistosomiasis: Life Cycle, Diagnosis, and Control","volume":"9","author":"ML Nelwan","year":"2019","journal-title":"Curr Ther Res Clin Exp"},{"key":"pntd.0009866.ref002","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.3389\/fimmu.2018.03042","article-title":"Schistosome Egg Migration: Mechanisms, Pathogenesis and Host Immune Responses","volume":"9","author":"A Costain","year":"2018","journal-title":"Front Immunol"},{"issue":"3","key":"pntd.0009866.ref003","first-page":"212","article-title":"Hepatobiliary Schistosomiasis","volume":"2","author":"Y Shaker","year":"2014","journal-title":"JCTH"},{"key":"pntd.0009866.ref004","doi-asserted-by":"crossref","first-page":"101341","DOI":"10.1016\/j.cimid.2019.101341","article-title":"Biological and proteomic studies of Schistosoma mansoni with decreased sensitivity to praziquantel","volume":"66","author":"IF Abou-El-Naga","year":"2019","journal-title":"Comp Immunol Microbiol Infect Dis"},{"key":"pntd.0009866.ref005","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.actatropica.2018.02.005","article-title":"Towards elimination of schistosomiasis after 5000 years of endemicity in Egypt","volume":"181","author":"IF Abou-El-Naga","year":"2018","journal-title":"Acta Trop"},{"issue":"5","key":"pntd.0009866.ref006","doi-asserted-by":"crossref","first-page":"787","DOI":"10.4269\/ajtmh.2011.10-0685","article-title":"Schistosomiasis among young children in Usoma, Kenya","volume":"84","author":"JR Verani","year":"2011","journal-title":"Am J Trop Med Hyg"},{"issue":"8","key":"pntd.0009866.ref007","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.4049\/jimmunol.140.8.2737","article-title":"In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. 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