title: Frequent nasal administrations of recombinant cholera toxin B subunit (rCTB)-containing tetanus and diphtheria toxoid vaccines induced antigen-specific serum and mucosal immune responses in the presence of anti-rCTB antibodies.
abstract: Vaccination via a mucosal route is a very attractive means for immunization, because both local and systemic immune responses are inducible and vaccines can be administered easily and safely from infants to elderly persons. For developing widely applicable mucosal vaccines using recombinant cholera toxin B subunit (rCTB) as a safe adjuvant, we examined whether frequent nasal administrations of rCTB-containing same and different vaccines could induce antigen-specific immune responses without induction of systemic tolerance and suppression by pre-existing anti-rCTB immunity. Ten repetitive nasal administrations to mice of tetanus toxoid (TT) + rCTB or diphtheria toxoid (DT) + rCTB raised and maintained high levels of antigen- and rCTB-specific serum IgG including high levels of tetanus/diphtheria antitoxin titres and raised nasal, salivary, lung, vaginal and fecal secreted IgA, suggesting that the regimen did not induce systemic tolerance to TT/DT and rCTB. Mice successively received repetitive five doses of TT as the first antigen and subsequent five doses of DT as the second antigen, and vice versa, raised serum IgG to the second antigen at various levels including low but sufficient protective levels of antitoxin titres and induced mucosal IgA in the lungs, the vaginas and feces, but hardly in the nasal secretions and salivas. After an interval of 22 weeks between the dosage of the first and second antigens, mice induced serum IgG to the second antigen at high levels and mucosal IgA in all sites. In conclusion, anti-TT and -DT serum and mucosal antibody responses induced by repeated intranasal immunization using rCTB adjuvant lasted for a long period, and for improving the effectivity of vaccination, different rCTB-containing vaccines should be administered at appropriate intervals.
authors.affiliation: Department of Microbiology, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan. yyasuda@med.nagoya-cu.ac.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Masanori
authors.initials: M
authors.lastname: Isaka
authors.forename: Tooru
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Keiko
authors.initials: K
authors.lastname: Matano
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Matsui
authors.forename: Kazunori
authors.initials: K
authors.lastname: Morokuma
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Maeyama
authors.forename: Kunio
authors.initials: K
authors.lastname: Ohkuma
authors.forename: Norihisa
authors.initials: N
authors.lastname: Goto
authors.forename: Kunio
authors.initials: K
authors.lastname: Tochikubo
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; D002772:Cholera Toxin