A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses.
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 glutelin GluB-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.
Takagi
Hidenori
H
Plant Biotechnology Department, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602, Japan.
Hiroi
Takachika
T
Yang
Lijun
L
Tada
Yoshifumi
Y
Yuki
Yoshikazu
Y
Takamura
Kaoru
K
Ishimitsu
Ryotaro
R
Kawauchi
Hideyuki
H
Kiyono
Hiroshi
H
Takaiwa
Fumio
F
D000485:Allergens / Q000276:immunology; D000818:Animals; D052179:Antigens, Plant; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D032485:Cryptomeria / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D005916:Globulins; D005983:Glutens / Q000235:genetics; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D012275:Oryza / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology; D030821:Plants, Genetically Modified; D011058:Pollen / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012639:Seeds / Q000378:metabolism; D030262:Soybean Proteins; D014612:Vaccines / Q000276:immunology*
D000485:Allergens; D052179:Antigens, Plant; C065290:Cry j I protein, Cryptomeria japonica; C065291:Cry j II protein, Cryptomeria japonica; D018984:Epitopes, T-Lymphocyte; D005916:Globulins; C120054:GluB-1 protein, Oryza; D010940:Plant Proteins; D030262:Soybean Proteins; D014612:Vaccines; D007073:Immunoglobulin E; D005983:Glutens; C011474:glycinin