title: Flagellin-PAc Fusion Protein Inhibits Progression of Established Caries.
abstract: Dental caries remains one of the most common infectious diseases of humankind, which develops slowly throughout life, affecting children, adolescents, and adults. A vaccine against caries is urgently needed. We previously developed recombinant flagellin as a mucosal adjuvant for anti-Streptococcus mutans vaccines by nasal immunization. Furthermore, we demonstrated a fusion protein strategy that combined flagellin and the target surface adhesion protein (PAc) in a single construct. This construct enhanced specific IgA responses in oral fluids and provided improved prophylactic protection against caries. In the present study, we observed prolonged progression of dental caries in rats after S. mutans Ingbritt challenge. In addition, we observed a therapeutic effect of the flagellin-PAc fusion protein (KF-rPAc) against dental caries as a mucosal vaccine with a new immunization protocol. The present study demonstrated that KF-rPAc by nasal immunization can promote PAc-specific systemic and mucosal antibody responses and inhibit dental caries progression efficiently after the implant of S. mutans into the oral cavity of the rats. The rats immunized with KF-rPAc exhibited 53.9% caries reduction compared with the sham-immunized rats. Our data support the concept of administration of KF-rPAc to humans after infection and even caries that has begun to alleviate caries progression. In conclusion, our study demonstrated that KF-rPAc could be used as an anticaries therapeutic mucosal vaccine.
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China Animal Biosafety Level III Laboratory at the Center for Animal Experiment, Wuhan University, Wuhan, Hubei, China.
authors.forename: R
authors.initials: R
authors.lastname: Bao
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: D H
authors.initials: DH
authors.lastname: Zhou
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: Y M
authors.initials: YM
authors.lastname: Li
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: B L
authors.initials: BL
authors.lastname: Zhao
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China hmyan@wh.iov.cn zmh@wh.iov.cn.
authors.forename: M H
authors.initials: MH
authors.lastname: Zhong
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors.forename: H M
authors.initials: HM
authors.lastname: Yan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage; D003731:Dental Caries / Q000382:microbiology / Q000517:prevention & control*; D003743:Dental Enamel / Q000473:pathology; D003804:Dentin / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005408:Flagellin / Q000276:immunology*; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012463:Saliva / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013295:Streptococcus mutans / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D005408:Flagellin
keywords: Streptococcus mutans; immunoglobulin A; intranasal immunization; rats; saliva; therapeutic vaccine