• Open Access

Prevention of allergic asthma by vaccination with transgenic rice seed expressing mite allergen: induction of allergen-specific oral tolerance without bystander suppression

Authors

  • Kazuya Suzuki,

    1. Transgenic Crop Research and Development Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, Japan
    2. Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan
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  • Osamu Kaminuma,

    1. Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan
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  • Lijun Yang,

    1. Transgenic Crop Research and Development Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, Japan
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  • Toshiro Takai,

    1. Atopy (Allergy) Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
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  • Akio Mori,

    1. Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan
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  • Makiko Umezu-Goto,

    1. Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan
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  • Takayuki Ohtomo,

    1. Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan
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  • Yasushi Ohmachi,

    1. Department of Advanced Technologies for Radiation Protection Research, National Institute of Radiological Sciences, Chiba, Chiba, Japan
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  • Yuko Noda,

    1. Department of Advanced Technologies for Radiation Protection Research, National Institute of Radiological Sciences, Chiba, Chiba, Japan
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  • Sakiko Hirose,

    1. Transgenic Crop Research and Development Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, Japan
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  • Ko Okumura,

    1. Atopy (Allergy) Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
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  • Hideoki Ogawa,

    1. Atopy (Allergy) Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
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  • Kazuko Takada,

    1. Department of Oral Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan
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  • Masatomo Hirasawa,

    1. Department of Oral Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan
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  • Takachika Hiroi,

    Corresponding author
    1. Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan
      (Tel +81 3 5316 3126 fax +81 3 5316 3153; email hiroi-tk@igakuken.or.jp) and
      (Tel +81 29 838 8373; fax +81 29 838 8397; email takaiwa@nias.affrc.go.jp)
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  • Fumio Takaiwa

    Corresponding author
    1. Transgenic Crop Research and Development Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, Japan
      (Tel +81 3 5316 3126 fax +81 3 5316 3153; email hiroi-tk@igakuken.or.jp) and
      (Tel +81 29 838 8373; fax +81 29 838 8397; email takaiwa@nias.affrc.go.jp)
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(Tel +81 3 5316 3126 fax +81 3 5316 3153; email hiroi-tk@igakuken.or.jp) and
(Tel +81 29 838 8373; fax +81 29 838 8397; email takaiwa@nias.affrc.go.jp)

Summary

This study tested the feasibility of oral immunotherapy for bronchial asthma using a newly developed subunit vaccine in which a fragment (p45–145) of mite allergen (Der p 1) containing immunodominant human and mouse T cell epitopes was encapsulated in endoplasmic reticulum-derived protein bodies of transgenic (Tg) rice seed. Allergen-specific serum immunoglobulin responses, T cell proliferation, Th1/Th2 cytokine production, airway inflammatory cell infiltration, bronchial hyper-responsiveness (BHR) and lung histology were investigated in allergen-immunized and -challenged mice. Prophylactic oral vaccination with the Tg rice seeds clearly reduced the serum levels of allergen-specific IgE and IgG. Allergen-induced CD4+ T cell proliferation and production of Th2 cytokines in vitro, infiltration of eosinophils, neutrophils and mononuclear cells into the airways and BHR were also inhibited by oral vaccination. The effects of the vaccine were antigen-specific immune response because the levels of specific IgE and IgG in mice immunized with Der f 2 or ovalbumin were not significantly suppressed by oral vaccination with the Der p 1 expressing Tg rice. Thus, the vaccine does not induce nonspecific bystander suppression, which has been a problem with many oral tolerance regimens. These results suggest that our novel vaccine strategy is a promising approach for allergen-specific oral immunotherapy against allergic diseases including bronchial asthma.

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