A bacterial flagellin, Vibrio vulnificus FlaB, has a strong mucosal adjuvant activity to induce protective immunity.
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.
Lee
Shee Eun
SE
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.
Kim
Soo Young
SY
Jeong
Byung Chul
BC
Kim
Young Ran
YR
Bae
Soo Jang
SJ
Ahn
Ouk Seon
OS
Lee
Je-Jung
JJ
Song
Ho-Chun
HC
Kim
Jung Mogg
JM
Choy
Hyon E
HE
Chung
Sun Sik
SS
Kweon
Mi-Na
MN
Rhee
Joon Haeng
JH
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*
D000276:Adjuvants, Immunologic; D016209:Interleukin-8; D016328:NF-kappa B; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin; C416532:flaB flagellin