title: A bacterial flagellin, Vibrio vulnificus FlaB, has a strong mucosal adjuvant activity to induce protective immunity.
abstract: Flagellin, the structural component of flagellar filament in various locomotive bacteria, is the ligand for Toll-like receptor 5 (TLR5) of host cells. TLR stimulation by various pathogen-associated molecular patterns leads to activation of innate and subsequent adaptive immune responses. Therefore, TLR ligands are considered attractive adjuvant candidates in vaccine development. In this study, we show the highly potent mucosal adjuvant activity of a Vibrio vulnificus major flagellin (FlaB). Using an intranasal immunization mouse model, we observed that coadministration of the flagellin with tetanus toxoid (TT) induced significantly enhanced TT-specific immunoglobulin A (IgA) responses in both mucosal and systemic compartments and IgG responses in the systemic compartment. The mice immunized with TT plus FlaB were completely protected from systemic challenge with a 200x minimum lethal dose of tetanus toxin. Radiolabeled FlaB administered into the nasal cavity readily reached the cervical lymph nodes and systemic circulation. FlaB bound directly to human TLR5 expressed on cultured epithelial cells and consequently induced NF-kappaB and interleukin-8 activation. Intranasally administered FlaB colocalized with CD11c as patches in putative dendritic cells and caused an increase in the number of TLR5-expressing cells in cervical lymph nodes. These results indicate that flagellin would serve as an efficacious mucosal adjuvant inducing protective immune responses through TLR5 activation.
authors.affiliation: National Research Laboratory of Molecular Microbial Pathogenesis and Department of Microbiology, Chonnam National University Medical School, 5 Hak-Dong, Dong-Ku, Gwangju 501-746, South Korea.
authors.forename: Shee Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Jeong
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Kim
authors.forename: Soo Jang
authors.initials: SJ
authors.lastname: Bae
authors.forename: Ouk Seon
authors.initials: OS
authors.lastname: Ahn
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Ho-Chun
authors.initials: HC
authors.lastname: Song
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.forename: Hyon E
authors.initials: HE
authors.lastname: Choy
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Chung
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
authors.forename: Joon Haeng
authors.initials: JH
authors.lastname: Rhee
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005408:Flagellin / Q000008:administration & dosage*; D006801:Humans; D018928:Immunity, Mucosal; D016209:Interleukin-8 / Q000096:biosynthesis; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051198:Toll-Like Receptor 5 / Q000502:physiology; D014735:Vibrio Infections / Q000276:immunology*; D041261:Vibrio vulnificus / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016209:Interleukin-8; D016328:NF-kappa B; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin; C416532:flaB flagellin