Generation of oral vaccine for mite allergy

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In this study, we have tried to elucidate the immunochemical properties of important house dust mite allergens applicable for recombinant oral vaccines. We identified novel dust mite antigens including group 16 major allergen Der f 16 (gelsolin family), group 17 allergen Der f 17 (EF-hand calcium binding allergen), and a new allergen Mag133 (UK114 family member).These new allergens have quite intriguing characteristics when considering then application to oral vaccine. We found that calcium binding to Der f 17 is critical for its IgE binding activity, and that the Der f 17 mutant that was deficient for calcium binding impaired IgE reactivity. These results suggest that the Der f 17 mutant is useful for generating "hypoallergenic vaccine", which can induces T cell response without anaphylactic side effect.Regarding Mag133, we found that this allergen had a Th2-skewing potency in addition to its high IgE binding property, implicating that Mag133 might play a role in the skewed Th2 response frequently seen in mite-allergic patients.We also analyzed Th1/Th2 cytokine production response to Der f 14, another important major allergen which also has potent T cell stimulatory activity. We found differential Th1/Th2 cytokine secretion in response to Der f 14 fragments ; Der f 14 N-terminal fragment triggered exclusive Th2 response, whereas internal Mag 3 fragment conversely induced Th1-dominated response. This differential cytokine regulation by Der f 14 fragments could be useful for T cell-targeted vaccine design that can ameliorate pathogenic Th2 response. Especially, Mag 3 might be effective for Th1-inducing vaccine. The N-terminal fragment could easily be engineered to Th1-inducing vaccine by conjugating with Th1 adjuvants.Taken together, we believe that the results obtained by this project should provide insights into the generation of anti-mite allergy oral vaccines for the next generation.