{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:37:49Z","timestamp":1793129869641,"version":"4.5.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["HHSN272201800043C"],"award-info":[{"award-number":["HHSN272201800043C"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["R01AI169781"],"award-info":[{"award-number":["R01AI169781"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      (Pa) is a ubiquitous, opportunistic nosocomial pathogen that poses a significant threat due to its innate and acquired multidrug resistance. Novel vaccine strategies are urgently needed for vulnerable populations, many of which harbor pre-existing immunity from prior encounters with Pa. Here, we evaluated a multivalent subunit vaccine combining type III secretion system (T3SS) antigens and exolysin A (ExlA) in a nanoemulsion formulation using a clinically relevant murine pulmonary pre-exposure model. This approach allowed us to determine whether vaccination could overcome the limitations of the host\u2019s initial, ineffective immune response. Vaccination fundamentally transforms suboptimal baseline memory into a potent, multi-faceted Th1\/Th17-polarized response. This globally transformed signature was characterized by significantly enhanced antigen-specific IFN-\n                      <jats:italic toggle=\"yes\">\u03b3<\/jats:italic>\n                      and IL-17A production, both locally and systematically in the lung, with exceptionally large biological effect sizes (Cohen\u2019s\n                      <jats:italic toggle=\"yes\">d<\/jats:italic>\n                      values reaching 21.35). By utilizing log10 transformation to accurately reflect pathogen growth kinetics, we demonstrated that this vaccine-augmented immunity conferred statistically significant protection following heterologous challenge. In the twice-exposed cohort, vaccination promoted superior bacterial clearance of the T3SS-positive strain, though clearance of the ExlA-positive strain was not enhanced, potentially due to immunological interference from pre-existing T3SS memory. In the thrice-exposed cohort, a functional protective threshold was observed, where high levels of natural immunity matched the vaccine-induced clearance levels. Our findings established that our vaccine formulation can effectively boost and redirect pre-existing immunity, offering a promising approach to overcome the limitations of natural exposure and protect at-risk individuals from diverse Pa infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00175-26","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:10:55Z","timestamp":1785867055000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A multivalent subunit vaccine augments pre-existing immunity to protect against T3SS-positive\n                    <i>Pseudomonas aeruginosa<\/i>\n                    but reveals immunological interference against ExlA-positive strains"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3170-9851","authenticated-orcid":true,"given":"Debaki R.","family":"Howlader","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology & Integrative Biomedical Sciences and the Bond Life Sciences Center, University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayan","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, University of Maryland","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satabdi","family":"Biswas","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology & Integrative Biomedical Sciences and the Bond Life Sciences Center, University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zackary K.","family":"Dietz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology & Integrative Biomedical Sciences and the Bond Life Sciences Center, University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-8694","authenticated-orcid":true,"given":"Robert K.","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, University of Maryland","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Picking","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology & Integrative Biomedical Sciences and the Bond Life Sciences Center, University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7998-0643","authenticated-orcid":true,"given":"Wendy L.","family":"Picking","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology & Integrative Biomedical Sciences and the Bond Life Sciences Center, University of Missouri","place":["Columbia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01635-6"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00477-5"},{"key":"e_1_3_5_4_2","volume-title":"Global antimicrobial resistance and use surveillance system (GLASS) report 2022","year":"2022","unstructured":"2022. Global antimicrobial resistance and use surveillance system (GLASS) report 2022. 1st ed. Antimicrobial Resistance Division (AMR), World Health Organization, Geneva.","edition":"1"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02185-7"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S446696"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01056-1"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10311-021-01274-z"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10071100"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2014.890053"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583008"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.706157"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00618-w"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1372349"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathophysiology30020014"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01900"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.07.009"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e18119"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02250-16"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.02.024"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2015.1046660"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26052012"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-025-00738-2"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.04.022"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00746-9"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.80"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1279837"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aas9673"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/jimmun\/vkag052"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.12.001"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaw2262"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.027"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2015.06.003"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00175-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00175-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:17:14Z","timestamp":1793128634000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00175-26"}},"subtitle":[],"editor":[{"given":"Jingren","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,8]]}},"alternative-id":["10.1128\/iai.00175-26"],"URL":"https:\/\/doi.org\/10.1128\/iai.00175-26","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]},"assertion":[{"value":"2026-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00175-26"}}