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Characterization of the Recombinant Der F 2 Mutant C8/119S and Evaluation of C8/119S in a Rder F 2-Sensitized Rhinitis Mice Model

Satoshi Koyanagi*, Toshio Murakami, Kazuyuki Nakashima, Toshihiro Maeda, Yoshinobu Miyatsu, Keishin Sugawara and Hiroshi Mizokami

Immunotherapy is the only curative approach to treat allergy, but carries the risk of anaphylaxis. C8/119S is a mutant of Der f 2, which is one of the causative allergens of perennial allergic diseases, and has been selected to decrease the risk of anaphylaxis in immunotherapy. In this study, the physical properties of C8/119S were determined, and the efficacy of C8/119S was evaluated in a NC/Nga mouse rhinitis model. C8/119S and recombinant Der f 2 (rDer f 2) were expressed in Escherichia coli . Purified allergens were analyzed by physicochemical and immunological techniques. In addition, rhinitis was provoked in rDer f 2-sensitized NC/Nga mice by nasal administration of rDer f 2, and C8/119S was administered. After provocation tests with rDer f 2, the number of eosinophils infiltrating the nasal mucosa was determined. C8/119S had a disordered structure, and the binding activity of allergic patients’ IgE to C8/119S was decreased compared with rDer f 2. In the NC/Nga mouse rhinitis model, eosinophil infiltration provoked by rDer f 2 was significantly controlled by the administration of C8/119S. Although similar therapeutic effects were also observed with rDer f 2 administration, 11 of 20 animals died during the rDer f 2 treatment period. On the other hand, no deaths occurred during C8/119S treatment. C8/119S appears to be an effective allergen vaccine for immunotherapy in patients with mite allergy and also appears to be safer than wild-type allergen vaccines.