{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:50Z","timestamp":1792790390538,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,14]]},"group-title":"Immunology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["AI158749-05"],"award-info":[{"award-number":["AI158749-05"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institutes of Health","award":["T32TR005120"],"award-info":[{"award-number":["T32TR005120"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Small extracellular vesicles (sEVs) released by infected cells carry microbial antigens together with host immunomodulatory molecules, yet whether their structural integrity governs the durability of protective immunity is unknown. Using\n                  <jats:italic>Salmonella<\/jats:italic>\n                  infection as a model, we show that sEVs isolated from infected macrophages act as potent antigen carriers for intranasal immunization. In BALB\/c mice, intact sEVs elicited antigen-specific serum IgG responses comparable in magnitude to those induced by live attenuated \u0394\n                  <jats:italic>aroA Salmonella.<\/jats:italic>\n                  Immunization further increased fecal IgA binding to\n                  <jats:italic>Salmonella<\/jats:italic>\n                  following lethal challenge and generated serum capable of enhancing macrophage-mediated bacterial uptake. Single-cell RNA sequencing of mesenteric lymph nodes revealed enrichment of mature B cells, effector CD8 T cells, and central memory\u2013like CD4 T cells expressing CD69, CD44, CCR7, and Sell\/CD62L, while defined recombinant sEV-associated antigens drove IFN-\u03b3 and IL-2 production by memory T cells ex vivo. Disrupting vesicle architecture by sonication left total IgG and IgG1 induction intact but selectively impaired IgG2a responses and antigen-specific T-cell recall; intact sEVs, by contrast, drove greater dendritic-cell CD80 expression, IL-2 production by cocultured CD69+ CD4 T cells, and prolonged survival after lethal challenge. These findings establish that vesicle integrity is dispensable for the overall magnitude of antibody induction but is required to instruct dendritic-cell costimulation, Th1-associated IgG2a class switching, and durable memory T-cell recall after mucosal immunization, identifying infection-derived sEVs as structurally organized immunogens rather than passive antigen reservoirs.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"750371v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.09.750371","type":"posted-content","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:25:11Z","timestamp":1789446311000},"source":"Crossref","is-referenced-by-count":0,"title":["Vesicle architecture licenses antigen-specific memory T cell immunity after mucosal immunization with infection-derived vesicles"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-5235","authenticated-orcid":false,"given":"Saloni","family":"Bhimani","sequence":"first","affiliation":[{"name":"Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0183-5056","authenticated-orcid":false,"given":"Alexander C.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States of America"},{"name":"Clinical and Translational Science Institute, University of Florida, Gainesville, FL, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0459-7716","authenticated-orcid":false,"given":"Mariola J.","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States of America"},{"name":"Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091810252420000_2026.09.09.750371v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(23)00606-X"},{"key":"2026091810252420000_2026.09.09.750371v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26093981"},{"key":"2026091810252420000_2026.09.09.750371v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9020165"},{"key":"2026091810252420000_2026.09.09.750371v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04003-z"},{"key":"2026091810252420000_2026.09.09.750371v1.5","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00219-20"},{"key":"2026091810252420000_2026.09.09.750371v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00999.x"},{"key":"2026091810252420000_2026.09.09.750371v1.7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.61.9.3981-3984.1993"},{"key":"2026091810252420000_2026.09.09.750371v1.8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03155"},{"key":"2026091810252420000_2026.09.09.750371v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2023.09.011"},{"key":"2026091810252420000_2026.09.09.750371v1.10","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-4593481\/v1"},{"key":"2026091810252420000_2026.09.09.750371v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00763-8"},{"key":"2026091810252420000_2026.09.09.750371v1.12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.946422"},{"key":"2026091810252420000_2026.09.09.750371v1.13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81131"},{"key":"2026091810252420000_2026.09.09.750371v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.07.009"},{"key":"2026091810252420000_2026.09.09.750371v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nm0598-594"},{"key":"2026091810252420000_2026.09.09.750371v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.09.015"},{"key":"2026091810252420000_2026.09.09.750371v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12267"},{"key":"2026091810252420000_2026.09.09.750371v1.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009465"},{"key":"2026091810252420000_2026.09.09.750371v1.19","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12327"},{"key":"2026091810252420000_2026.09.09.750371v1.20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601357"},{"key":"2026091810252420000_2026.09.09.750371v1.21","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-263"},{"key":"2026091810252420000_2026.09.09.750371v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"2026091810252420000_2026.09.09.750371v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/334255a0"},{"key":"2026091810252420000_2026.09.09.750371v1.24","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00158.x"},{"key":"2026091810252420000_2026.09.09.750371v1.25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-682377"},{"key":"2026091810252420000_2026.09.09.750371v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.07.013"},{"key":"2026091810252420000_2026.09.09.750371v1.27","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02329-2"},{"key":"2026091810252420000_2026.09.09.750371v1.28","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202000908"},{"key":"2026091810252420000_2026.09.09.750371v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/ni854"},{"key":"2026091810252420000_2026.09.09.750371v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-10050-w"},{"key":"2026091810252420000_2026.09.09.750371v1.31","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12163"},{"key":"2026091810252420000_2026.09.09.750371v1.32","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00720-08"},{"key":"2026091810252420000_2026.09.09.750371v1.33","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.12.6953-6961.2003"},{"key":"2026091810252420000_2026.09.09.750371v1.34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002966"},{"key":"2026091810252420000_2026.09.09.750371v1.35","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-263"},{"key":"2026091810252420000_2026.09.09.750371v1.36","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01905-06"},{"key":"2026091810252420000_2026.09.09.750371v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nm1592"},{"key":"2026091810252420000_2026.09.09.750371v1.38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801592"},{"key":"2026091810252420000_2026.09.09.750371v1.39","unstructured":"Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites | Nature Medicine [Internet]. [cited 2026 Aug 4]. Available from: https:\/\/www.nature.com\/articles\/nm1108#Sec10"},{"key":"2026091810252420000_2026.09.09.750371v1.40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006349"},{"key":"2026091810252420000_2026.09.09.750371v1.41","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142101"},{"key":"2026091810252420000_2026.09.09.750371v1.42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1628756"},{"key":"2026091810252420000_2026.09.09.750371v1.43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010004"},{"key":"2026091810252420000_2026.09.09.750371v1.44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02966"},{"key":"2026091810252420000_2026.09.09.750371v1.45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700952"},{"key":"2026091810252420000_2026.09.09.750371v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2025.127622"},{"key":"2026091810252420000_2026.09.09.750371v1.47","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otad030"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.09.750371","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:25:37Z","timestamp":1789752337000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.09.750371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":47,"URL":"https:\/\/doi.org\/10.64898\/2026.09.09.750371","relation":{},"subject":[],"published":{"date-parts":[[2026,9,14]]},"subtype":"preprint"}}