A nontoxic chimeric enterotoxin adjuvant induces protective immunity in both mucosal and systemic compartments with reduced IgE antibodies.

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:
  • The Journal of infectious diseases

دوره 186 9  شماره 

صفحات  -

تاریخ انتشار 2002