Oral Immunotherapy with a Phosphorylated Hypoallergenic Allergen Ameliorates Allergic Responses More Effectively Than Intact Allergen in a Murine Model of Buckwheat Allergy

Scope Buckwheat is a common food allergen frequently consumed in Asian countries, with Fag e 1 and Fag e 2 being the major buckwheat allergens. The purpose of this study is to prepare an oral immunotherapy agent by attenuating these allergens via phosphorylation. The immunomodulatory effects of phosphorylated Fag e 2 (P‐Fag e 2) in a mouse model of buckwheat allergy are evaluated. Methods and results Phosphorylated Fag e 1 (P‐Fag e 1) and P‐Fag e 2 are prepared by dry‐heating in the presence of pyrophosphate. Subsequent dot‐blot analysis using serum from food‐allergic patient indicates that both proteins exhibit reduced allergenicity upon phosphorylation. Mice subjected to oral administration of P‐Fag e 2 for 6 weeks exhibit decreased specific serum IgE and increased specific IgA after Fag e 2 sensitization compared to the sham‐treated mice. Moreover, the Peyer's patches (PP) of phosphorylated antigen‐fed mice show decreased IL‐4 production and induction of T follicular helper (Tfh) cells. Increased production of IL‐6 is observed in the CD11c+ cells isolated from the PPs of P‐Fag e 2‐fed mice. Conclusion These results indicate that attenuated allergens can suppress Th2‐induced allergic responses via induction of Tfh cells, which are regulated by IL‐6 secreted from dendritic cells. Fag e 1 and Fag e 2 are major allergens in buckwheat. Phosphorylation of Fag e 1 and Fag e 2 result in reduced allergenicity owing to the masking effect of IgE‐binding epitopes. Mice fed phosphorylated‐Fag e 2 exhibit attenuated Th2‐mediated allergic reactions. Suppression of the allergic response is primarily due to induction of Tfh cells, which is regulated by IL‐6 secreted from dendritic cells.