Open AccessA rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses
Author(s) -
Hidenori Takagi,
Takachika Hiroi,
Lijian Yang,
Yutaka Tada,
Yoshikazu Yuki,
Kaoru Takamura,
Ryotaro Ishimitsu,
Hideyuki Kawauchi,
Hiroshi Kiyono,
Fumio Takaiwa
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0503428102
Subject(s) - epitope , immunoglobulin e , biology , allergen , t cell , genetically modified rice , immunology , fusion protein , antibody , microbiology and biotechnology , allergy , transgene , genetically modified crops , immune system , biochemistry , gene , recombinant dna
Peptide immunotherapy using multiple predominant allergen-specific T cell epitopes is a safe and promising strategy for the control of type I allergy. In this study, we developed transgenic rice plants expressing mouse dominant T cell epitope peptides of Cry j I and Cry j II allergens of Japanese cedar pollen as a fusion protein with the soybean seed storage protein glycinin. Under the control of the rice seed storage protein glutelinGluB-1 promoter, the fusion protein was specifically expressed and accumulated in seeds at a level of 0.5% of the total seed protein. Oral feeding to mice of transgenic rice seeds expressing the T cell epitope peptides of Cry j I and Cry j II before systemic challenge with total protein of cedar pollen inhibited the development of allergen-specific serum IgE and IgG antibody and CD4+ T cell proliferative responses. The levels of allergen-specific CD4+ T cell-derived allergy-associated T helper 2 cytokine production of IL-4, IL-5, and IL-13 and histamine release in serum were significantly decreased. Moreover, the development of pollen-induced clinical symptoms was inhibited in our experimental sneezing mouse model. These results indicate the potential of transgenic rice seeds in production and mucosal delivery of allergen-specific T cell epitope peptides for the induction of oral tolerance to pollen allergens.