{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:24:59Z","timestamp":1784118299495,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation (NRF) of Korea","award":["2020R1A5A2031185"],"award-info":[{"award-number":["2020R1A5A2031185"]}]},{"name":"National Research Foundation (NRF) of Korea","award":["2020M3A9G3080282"],"award-info":[{"award-number":["2020M3A9G3080282"]}]},{"name":"National Research Foundation (NRF) of Korea","award":["2019R1A5A2027521"],"award-info":[{"award-number":["2019R1A5A2027521"]}]},{"name":"National Research Foundation (NRF) of Korea","award":["RS-2022-KH127978(HV22C0079)"],"award-info":[{"award-number":["RS-2022-KH127978(HV22C0079)"]}]},{"name":"Korea Health Technology R&amp;D Project","award":["2020R1A5A2031185"],"award-info":[{"award-number":["2020R1A5A2031185"]}]},{"name":"Korea Health Technology R&amp;D Project","award":["2020M3A9G3080282"],"award-info":[{"award-number":["2020M3A9G3080282"]}]},{"name":"Korea Health Technology R&amp;D Project","award":["2019R1A5A2027521"],"award-info":[{"award-number":["2019R1A5A2027521"]}]},{"name":"Korea Health Technology R&amp;D Project","award":["RS-2022-KH127978(HV22C0079)"],"award-info":[{"award-number":["RS-2022-KH127978(HV22C0079)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Periodontal disease (PD) is caused by microbial dysbiosis and accompanying adverse inflammatory responses. Due to its high incidence and association with various systemic diseases, disease-modifying treatments that modulate dysbiosis serve as promising therapeutic approaches. In this study, to simulate the pathophysiological situation, we established a \u201ctemporary ligature plus oral infection model\u201d that incorporates a temporary silk ligature and oral infection with a cocktail of live Tannerella forsythia (Tf), Pophyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn) in mice and tested the efficacy of a new trivalent mucosal vaccine. It has been reported that Tf, a red complex pathogen, amplifies periodontitis severity by interacting with periodontopathic bacteria such as Pg and Fn. Here, we developed a recombinant mucosal vaccine targeting a surface-associated protein, BspA, of Tf by genetically combining truncated BspA with built-in adjuvant flagellin (FlaB). To simultaneously induce Tf-, Pg-, and Fn-specific immune responses, it was formulated as a trivalent mucosal vaccine containing Tf-FlaB-tBspA (BtB), Pg-Hgp44-FlaB (HB), and Fn-FlaB-tFomA (BtA). Intranasal immunization with the trivalent mucosal vaccine (BtB + HB + BtA) prevented alveolar bone loss and gingival proinflammatory cytokine production. Vaccinated mice exhibited significant induction of Tf-tBspA-, Pg-Hgp44-, and Fn-tFomA-specific IgG and IgA responses in the serum and saliva, respectively. The anti-sera and anti-saliva efficiently inhibited epithelial cell invasion by Tf and Pg and interfered with biofilm formation by Fn. The flagellin-adjuvanted trivalent mucosal vaccine offers a novel method for modulating dysbiotic bacteria associated with periodontitis. This approach leverages the adjuvant properties of flagellin to enhance the immune response, aiming to restore a balanced microbial environment and improve periodontal health.<\/jats:p>","DOI":"10.3390\/vaccines12070754","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:40:50Z","timestamp":1720449650000},"page":"754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Flagellin-Adjuvanted Trivalent Mucosal Vaccine Targeting Key Periodontopathic Bacteria"],"prefix":"10.3390","volume":"12","author":[{"given":"Vandara","family":"Loeurng","sequence":"first","affiliation":[{"name":"Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun 58128, Republic of Korea"},{"name":"Combinatorial Tumor Immunotherapy MRC, Chonnam National University Medical School, Hwasun-gun 58128, Republic of Korea"},{"name":"Department of Microbiology, Chonnam National University Medical School, Hwasun-gun 58128, Republic of Korea"},{"name":"National Immunotherapy Innovation Center, Hwasun-gun 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sao","family":"Puth","sequence":"additional","affiliation":[{"name":"Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun 58128, Republic of Korea"},{"name":"National Immunotherapy Innovation Center, Hwasun-gun 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seol Hee","family":"Hong","sequence":"additional","affiliation":[{"name":"Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun 58128, Republic of Korea"},{"name":"National Immunotherapy Innovation Center, Hwasun-gun 58128, Republic of Korea"},{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Suhk","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun 58128, Republic of Korea"},{"name":"National Immunotherapy Innovation Center, Hwasun-gun 58128, Republic of Korea"},{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0890-8692","authenticated-orcid":false,"given":"Kamalakannan","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6279-6487","authenticated-orcid":false,"given":"Jeong Tae","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong-Ki","family":"Kook","sequence":"additional","affiliation":[{"name":"Korean Collection of Oral Microbiology and Department of Oral Biochemistry, School of Dentistry, Chosun University, Gwangju 61452, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-3203","authenticated-orcid":false,"given":"Joon Haeng","family":"Rhee","sequence":"additional","affiliation":[{"name":"Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun 58128, Republic of Korea"},{"name":"Combinatorial Tumor Immunotherapy MRC, Chonnam National University Medical School, Hwasun-gun 58128, Republic of Korea"},{"name":"Department of Microbiology, Chonnam National University Medical School, Hwasun-gun 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2023-3317","authenticated-orcid":false,"given":"Shee Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Vaccine R&D Center, Chonnam National University, Hwasun-gun 58128, Republic of Korea"},{"name":"National Immunotherapy Innovation Center, Hwasun-gun 58128, Republic of Korea"},{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"ref_1","first-page":"72","article-title":"Prevalence of periodontal disease, its association with systemic diseases and prevention","volume":"11","author":"Nazir","year":"2017","journal-title":"Int. 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