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Oral Immunotherapy for Allergic Conjunctivitis Using Transgenic Rice Expressing Hypoallergenic Antigens

Fukuda, Ken, MD, PhD*; Ishida, Waka, MD, PhD; Wakasa, Yuhya, PhD; Takagi, Hidenori, PhD; Takaiwa, Fumio, PhD; Fukushima, Atsuki, MD, PhD*

doi: 10.1097/ICO.0000000000001758

Abstract: Pollinosis, or allergic conjunctivitis and rhinitis induced by pollen, is one of the most common diseases worldwide. In Japan, Japanese cedar (Cryptomeria japonica) pollinosis is a predominant allergic condition that affects more than one-third of all Japanese individuals. Pharmacological treatments of allergic conjunctivitis include administration of antiallergic eye drops containing an antihistamine or mast cell stabilizer. However, these topical treatments provide transient relief from symptoms. The only available curative treatment for allergic diseases is allergen-specific immunotherapy. Sublingual immunotherapy for pollinosis has been found to be effective for suppression of ocular and nasal symptoms, but patient compliance is low. Oral administration of staple foods engineered to express allergens is a possible means of delivering antigens for immunotherapy, and its convenience would be expected to improve compliance. With the aim of developing more convenient, effective, and safe immunotherapies for allergic diseases, we have generated rice-based edible vaccines expressing antigens derived from dust mites or pollen from Japanese cedar, birch, or ragweed. In this study, we summarize the results of our immunotherapy studies using transgenic rice. Oral immunotherapy with transgenic rice seeds containing hypoallergenic modified forms of Japanese cedar pollen antigens was effective for both preventing allergic conjunctivitis and suppressing established disease in mice. Oral administration of transgenic rice seeds is thus a promising approach to immunotherapy for conjunctivitis and rhinitis induced by Japanese cedar pollen.

*Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi, Japan; and

Plant Molecular Farming Unit, Division of Biotechnology, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization, Ibaraki, Japan.

Correspondence: Ken Fukuda, MD, PhD, Department of Ophthalmology and Visual Science, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan (e-mail:

K. Fukuda has received funding from the Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical's Founder and an honorarium and travel fees from Santen Pharmaceutical. K. Fukuda has also received grants from Otsuka Pharmaceutical Co., Ltd., Novartis Pharmaceuticals Japan (Novartis Pharma K.K.), and Alcon Japan, and payment for lectures from Alcon Japan Ltd., Kissei Pharmaceutical Co., Ltd., Torii Pharmaceutical Co., Ltd., Senju Pharmaceutical Co., Ltd., Santen Pharmaceutical Co., Ltd., Eisai Co., Ltd., Kowa Pharmaceutical Co., Ltd., and Otsuka Pharmaceutical Co., Ltd. F. Takaiwa and Y. Wakasa have received a grant from the Agri-Health Translational Research Projects of the Ministry of Agriculture, Forestry, and Fisheries of Japan. A. Fukushima has received a grant from JSPS KAKENHI (Grant Number: JP16K11324). The remaining authors have no funding or conflicts of interest to disclose.

Received June 29, 2018

Received in revised form July 23, 2018

Accepted July 24, 2018

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