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 | Mi-Na Kweon, Masafumi Yamamoto, Fumiko Watanabe, Shinichi Tamura, Frederik W Van Ginkel, Akira Miyauchi, Hiroaki Takagi, Yoshifumi Takeda, Takashi Hamabata, Kohtaro Fujihashi, Jerry R McGhee, Hiroshi Kiyono |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 186
Issue 9
Pg. 1261-9
(Nov 01 2002)
ISSN: 0022-1899 [Print] United States |
PMID | 12402195
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Bacterial Toxins
- Enterotoxins
- Escherichia coli Proteins
- Protein Subunits
- Recombinant Fusion Proteins
- Immunoglobulin E
- Cholera Toxin
- heat-labile enterotoxin, E coli
|
Topics |
- Amino Acid Sequence
- Amino Acid Substitution
- Animals
- Antibody Formation
(drug effects)
- Bacterial Toxins
(pharmacology)
- Base Sequence
- Cholera Toxin
(genetics, pharmacology)
- Cloning, Molecular
- Enterotoxins
(pharmacology)
- Escherichia coli
- Escherichia coli Proteins
- Immunity, Mucosal
(drug effects)
- Immunoglobulin E
(metabolism)
- Mice
- Molecular Sequence Data
- Polymerase Chain Reaction
- Protein Subunits
- Recombinant Fusion Proteins
(pharmacology)
- Restriction Mapping
|