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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.
AuthorsMi-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
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 186 Issue 9 Pg. 1261-9 (Nov 01 2002) ISSN: 0022-1899 [Print] United States
PMID12402195 (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

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