title: A nontoxic chimeric enterotoxin adjuvant induces protective immunity in both mucosal and systemic compartments with reduced IgE antibodies.
abstract: A novel nontoxic form of chimeric mucosal adjuvant that combines the A subunit of mutant cholera toxin E112K with the pentameric B subunit of heat-labile enterotoxin from enterotoxigenic Escherichia coli was constructed by use of the Brevibacillus choshinensis expression system (mCTA/LTB). Nasal immunization of mice with tetanus toxoid (TT) plus mCTA/LTB elicited significant TT-specific immunoglobulin A responses in mucosal compartments and induced high serum immunoglobulin G and immunoglobulin A anti-TT antibody responses. Although TT plus native CT induced high total and TT-specific immunoglobulin E responses, use of the chimera molecule as mucosal adjuvant did not. Furthermore, all mice immunized with TT plus mCTA/LTB were protected from lethal systemic challenge with tetanus toxin. Importantly, the mice were completely protected from influenza virus infection after nasal immunization with inactivated influenza vaccine together with mCTA/LTB. These results show that B. choshinensis-derived mCTA/LTB is an effective and safe mucosal adjuvant for the induction of protective immunity against potent bacterial exotoxin and influenza virus infection.
authors.affiliation: Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Fumiko
authors.initials: F
authors.lastname: Watanabe
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tamura
authors.forename: Frederik W
authors.initials: FW
authors.lastname: Van Ginkel
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takagi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamabata
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Jerry R
authors.initials: JR
authors.lastname: McGhee
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001483:Base Sequence; D002772:Cholera Toxin / Q000235:genetics / Q000494:pharmacology*; D003001:Cloning, Molecular; D004768:Enterotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D018928:Immunity, Mucosal / Q000187:drug effects; D007073:Immunoglobulin E / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015183:Restriction Mapping
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli