{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:24:30Z","timestamp":1788827070503,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Hypervirulent\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    (hvKP) variants represent urgent multidrug-resistant threats against which no licensed vaccine exists. FimA is indispensable for KP mucosal colonization and is thus a promising vaccine target; however, its protective immunodominant B-cell epitopes in vaccines with different adjuvants against KP remain undefined. Here, we revealed how adjuvants shape different hierarchies of the immunodominant B-cell epitopes of FimA and studied the humoral anti-FimA response and protective efficacy in a murine model of acute pneumonia. BALB\/c mice were intramuscularly immunized with recombinant FimA formulated in three clinically trialed adjuvants: AddaVax, AddaS03, and AlPO\n                    <jats:sub>4<\/jats:sub>\n                    , whereafter they were challenged with lethal doses of the hvKP YBQ strain. Under the experimental conditions used in this immunization-challenge model, AddaS03-immunized mice exhibited 100% survival and reduced pulmonary bacterial load, whereas AddaVax-immunized mice showed only 40% survival. Furthermore, FimA-immunized groups with different adjuvants exhibited different opsonophagocytic killing activities and inflammatory cytokine levels, likely explaining the variability in protective immunity. ELISA-based linear B-cell epitope mapping of FimA with different adjuvants revealed three novel immunodominant epitopes\u2014their hierarchies were altered by different adjuvants. Further, a causal link might exist between FimA epitope hierarchy and protective efficacy in hvKP-infected mice. Immunization with a mixture of these FimA immunodominant epitopes plus AlPO\n                    <jats:sub>4<\/jats:sub>\n                    achieved an 80% protection rate, where it exerted a potent therapeutic effect in combination with low-dose meropenem. Our findings revealed that adjuvants enhance anti-FimA immunity and modulate FimA epitope hierarchies across different vaccinated groups. Therefore, rational adjuvant selection may elicit effective FimA-induced responses in KP vaccines, wherein different FimA immunodominant epitopes induce protective humoral immune responses.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1796753","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:35:26Z","timestamp":1782102926000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Adjuvant-driven epitope hierarchy correlates with the protective efficacy of FimA vaccine against Klebsiella pneumoniae"],"prefix":"10.3389","volume":"17","author":[{"given":"Guangyang","family":"Ming","sequence":"first","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]},{"name":"Chongqing Huazhi Biopharmaceutical Co., Ltd.","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longlong","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengju","family":"Yan","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifu","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Gou","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yuan","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Jing","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Luo","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanming","family":"Zou","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University)","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjian","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Bioengineering, Chongqing University of Technology","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.2217\/fmb-2022-0097","article-title":"Klebsiella pneumoniae: an update on antibiotic resistance mechanisms","volume":"18","author":"Karami-Zarandi","year":"2023","journal-title":"Future Microbiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1186\/s40001-025-02717-x","article-title":"A systematic review on natural products with antimicrobial potential against WHO's priority pathogens","volume":"30","author":"SeyedAlinaghi","year":"2025","journal-title":"Eur J Med Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/s43856-025-01112-1","article-title":"Global trends of antimicrobial resistance and virulence of Klebsiella pneumoniae from different host 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