Prevention of allergic conjunctivitis in mice by a rice-based edible vaccine containing modified Japanese cedar pollen allergens.

Abstract

To determine whether oral immunotherapy with transgenic rice seeds expressing hypoallergenic modified antigens suppresses cedar pollen-induced allergic conjunctivitis by eliciting immune tolerance in mice. BALB/c mice were fed once a day for 20 days with 220 mg of transgenic rice expressing modified Japanese cedar pollen allergens Cry j 1 and Cry j 2 or with non-transgenic rice seeds as a control. They were then sensitised with two intraperitoneal injections of Japanese cedar pollen in alum before challenge twice with pollen in eye drops. Twenty-four hours after the second challenge, the conjunctiva, spleen, and blood were isolated for histological analysis, cytokine production assays, and measurement of serum immunoglobulin E concentrations, respectively. The numbers of eosinophils and total inflammatory cells in the conjunctiva were significantly lower in mice fed the transgenic rice than in those fed non-transgenic rice. The clinical score evaluated at 15 min after antigen challenge was also significantly lower in mice fed the transgenic rice than in those fed non-transgenic rice. The serum concentrations of both total and allergen-specific immunoglobulin E were also significantly lower in mice fed the transgenic rice. Oral vaccination with transgenic rice resulted in significant down-regulation of the allergen-induced production of interleukin (IL)-2, IL-4, IL-5, IL-12p70, interferon-γ, and IL-17A by splenocytes. Oral immunotherapy with transgenic rice expressing modified Japanese cedar pollen allergens suppressed pollen-induced experimental allergic conjunctivitis in mice by eliciting immune tolerance. This novel prophylactic approach is potentially safe and effective for allergen-specific oral immunotherapy in allergic conjunctivitis.