A nontoxic chimeric enterotoxin adjuvant induces protective immunity in both mucosal and systemic compartments with reduced IgE antibodies.
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.
Kweon
Mi-Na
MN
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Yamamoto
Masafumi
M
Watanabe
Fumiko
F
Tamura
Shinichi
S
Van Ginkel
Frederik W
FW
Miyauchi
Akira
A
Takagi
Hiroaki
H
Takeda
Yoshifumi
Y
Hamabata
Takashi
T
Fujihashi
Kohtaro
K
McGhee
Jerry R
JR
Kiyono
Hiroshi
H
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
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