Prophylactic and Therapeutic Effects of Oral Immunotherapy on Birch Pollen-Induced Allergic Conjunctivitis in Mice with a Rice-Based Edible Vaccine Expressing a Hypoallergenic Birch Pollen Allergen.

Waka Ishida,Fumio Takaiwa,Tatsuma Kishimoto,Ken Fukuda

doi:10.3390/cells10123361

Abstract

We investigated the prophylactic and therapeutic effects of the oral administration of transgenic rice seeds expressing a hypoallergenic Bet v 1 derivative of allergic birch pollen conjunctivitis in mice. Transgenic rice seed depositing a chimeric molecule called TPC7 (tree pollen chimera 7) created by DNA shuffling of Bet v 1 family sequences from birch, alder and hazel in protein bodies of endosperm was generated. BALB/c mice were sensitized to birch pollen in alum and challenged with pollen in eyedrops. They were fed TPC7 transgenic or non-transgenic (control) rice seeds for 14 d before sensitization (prophylactic protocol) or 17 d after sensitization (therapeutic protocol). The clinical score and number of conjunctival eosinophils were significantly lower in TPC7-fed mice than in the control mice based on both the prophylactic and therapeutic protocols. Serum concentration of allergen-specific IgE did not differ between TPC7-fed and control groups in either protocol. Prophylactic administration of TPC7 downregulated the production of IL-4 and IFN-γ, whereas therapeutic administration of TPC7 upregulated the production of IFN-γ by allergen-stimulated splenocytes. Prophylactic or therapeutic oral administration of transgenic rice expressing TPC7 suppressed birch pollen-induced allergic conjunctivitis in mice. Feeding transgenic rice is a potentially effective approach as an allergen-specific immunotherapy for allergic conjunctivitis.

Highlights

The prevalence of allergic diseases, including conjunctivitis, rhinitis, asthma, and atopic dermatitis, is rapidly increasing worldwide [1,2]
Allergen-specific immunotherapy is performed by the repeated administration of antigens via several different routes, including subcutaneous injections, sublingual application, and oral administration
We demonstrated that prophylactic and therapeutic oral administration of ovalbumin (OVA) suppressed OVA-induced experimental allergic conjunctivitis (EAC) in a mouse model, suggesting that OIT is a candidate for radical treatment of allergic conjunctivitis [17]

Summary

Introduction

The prevalence of allergic diseases, including conjunctivitis, rhinitis, asthma, and atopic dermatitis, is rapidly increasing worldwide [1,2]. The main therapeutic modality for allergic conjunctivitis is eye drops with antihistamines, mast cell stabilizers, and/or corticosteroids, regardless of the sensitized allergens. These medications can temporarily reduce clinical symptoms, they do not constitute a permanent cure. Successful treatment with allergen-specific immunotherapy has been reported in the past century for allergic rhinitis, conjunctivitis, and asthma [9,10,11]. OIT has been investigated as an alternative approach for treating food allergies. OIT in patients with pollinosis or allergic conjunctivitis has not been investigated

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