{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:10:32Z","timestamp":1786122632312,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Vaccines targeting avian influenza virus A\/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A\/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal in uenza A\/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT02921997?term=NCT02921997&amp;amp;viewType<\/jats:ext-link>\n                      , idientifier NCT02921997.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1786231","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T10:47:49Z","timestamp":1786099669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic and proteomic signatures following AS03-adjuvanted Influenza A\/H7N9 vaccine"],"prefix":"10.3389","volume":"17","author":[{"given":"C. Buddy","family":"Creech","sequence":"first","affiliation":[{"name":"Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University Medical Center","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen J.","family":"Steenbergen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science and Bioinformatics, The Emmes Company, LLC","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey E.","family":"Gelber","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science and Bioinformatics, The Emmes Company, LLC","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh M.","family":"Howard","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University Medical Center","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Schey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie Lindsey","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M.","family":"Yoder","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University Medical Center","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Vanderbilt Vaccine Research Program, Department of 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