Safety and efficacy of rice seed-based oral allergy vaccine for Japanese cedar pollinosis in Japanese monkeys

•Transgenic rice containing modified cedar pollen allergens was used as oral tolerogen.•Transgenic rice was orally administered to Japanese monkeys.•Sensitization to cedar pollen allergens was not observed in healthy monkeys.•Oral immune tolerance to cedar pollen allergens was induced in pollinosis monkeys. Japanese cedar (Cryptomeria japonica) pollinosis (JCP) is one of the major seasonal IgE-mediated type I allergies from February to April each year. Not only human patients but also Japanese monkeys (Macaca fuscata) are afflicted with this pollinosis in Japan, which exhibit similar clinical allergic symptoms such as allergenic rhinitis and conjunctivitis. Therefore, monkeys naturally sensitized to JC pollen allergens are expected to serve as a suitable animal model for exploiting the allergy vaccine for JCP, since allergen-specific immunotherapy is the only curative treatment for allergy diseases. We generated transgenic rice containing the hypoallergenic JC pollen Cry j 1 and Cry j 2 allergen derivatives as tolerogen. In this study, safety and efficacy of transgenic rice seed were evaluated by oral administration to Japanese monkeys. Healthy monkeys were not sensitized to Cry j 1 and Cry j 2 allergens, even when administered for one to ten months. By contrast, peripheral blood mononuclear cell (PBMC) proliferation and IgE antibody specific to these allergens were reduced in Japanese monkeys with JCP. Especially, suppression of allergen-specific PBMC proliferation was observed within only two months after administration. These findings indicate that this transgenic rice acts as effective tolerogen to induce oral immune tolerance against JC allergens.