{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:58:03Z","timestamp":1792180683526,"version":"4.4.0"},"reference-count":161,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Flagellin, an essential structural protein of bacterial flagella, has emerged as a potent modulator of both specific and nonspecific immunity, demonstrating significant potential as a vaccine adjuvant and carrier. By inducing the release of pro\u2010inflammatory cytokines like IL\u20101\u03b2, TNF\u2010\u03b1, IL\u20106, IL\u20108, and IL\u201012, flagellin activates the innate immune system, enhancing antigen\u2010specific adaptive immune responses mediated by tumour\u2010specific type 1 helper T cells and cytotoxic T cells, thus positioning it as a valuable adjuvant or complementary therapy for various cancers and infectious diseases. This review explores recent strategies, innovations, and clinical applications of flagellin\u2010based immunotherapies, particularly in the context of infectious diseases and cancers. Flagellin from <jats:styled-content style=\"fixed-case\">\n<jats:italic>Salmonella typhimurium<\/jats:italic>\n<\/jats:styled-content> has been extensively studied as a vaccine adjuvant for diseases like HIV, influenza, dengue, West Nile virus, poultry cholera, and bursal diseases and shows promise in treating lung metastasis, melanoma, colon, and prostate cancers. It has also proven effective against multidrug\u2010resistant bacteria, including <jats:styled-content style=\"fixed-case\">\n<jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">\n<jats:italic>S. typhimurium<\/jats:italic>\n<\/jats:styled-content>. Notably, <jats:styled-content style=\"fixed-case\">\n<jats:italic>S. typhimurium<\/jats:italic>\n<\/jats:styled-content> flagellin\u2010based vaccines for influenza have progressed to clinical trials. Additionally, flagellins from <jats:styled-content style=\"fixed-case\">\n<jats:italic>S. typhi<\/jats:italic>\n<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">\n<jats:italic>S. enteritidis<\/jats:italic>\n<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">\n<jats:italic>P. aeruginosa<\/jats:italic>\n<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">\n<jats:italic>Escherichia coli<\/jats:italic>\n<\/jats:styled-content> are being evaluated as vaccine candidates for plague, malaria, and infections caused by <jats:styled-content style=\"fixed-case\">\n<jats:italic>P. aeruginosa<\/jats:italic>\n<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">\n<jats:italic>E. coli<\/jats:italic>\n<\/jats:styled-content>. In cancer therapy, flagellin\u2010based treatments, especially when combined with tumour antigens, have exhibited the ability to enhance anti\u2010tumour immunity and improve patient outcomes. Other flagellin\u2010based vaccines derived from <jats:italic>S. Dublin<\/jats:italic>, <jats:italic>S. munchen<\/jats:italic>, and <jats:styled-content style=\"fixed-case\">\n<jats:italic>Vibrio vulnificus<\/jats:italic>\n<\/jats:styled-content> have been employed in the treatment of prostate, lung, liver, breast, cervical, and colorectal cancers, as well as lymphoma, melanoma, and radiation\u2010induced mucositis. Mobilan, a recombinant non\u2010replicating adenovirus vector expressing <jats:italic>Salmonella<\/jats:italic> flagellin, is currently in a phase Ib clinical trial for prostate cancer. Overall, bacterial flagellin treatments are generally safe, well\u2010tolerated, and associated with minimal side effects, making them a promising option for managing infectious diseases and cancers.<\/jats:p>","DOI":"10.1111\/imm.70001","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T03:23:39Z","timestamp":1749525819000},"page":"277-303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Flagellins as Vaccine Adjuvants and Cancer Immunotherapy: Recent Advances and Future Prospects"],"prefix":"10.1111","volume":"176","author":[{"given":"Asma","family":"Talukder","sequence":"first","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2294-1314","authenticated-orcid":false,"given":"Md. Mijanur","family":"Rahman","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Sifat","family":"Rahi","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean L.","family":"Pountney","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Q.","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences Griffith University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1168"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/1040841X.2021.1970512"},{"key":"e_1_2_11_4_1","volume-title":"Fluid Dynamics, Ecology, and 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