Effects of oral hyposensitization with recombinant Der f2 on immediate airway constriction in a murine allergic model

Abstract

Recombinant Der f2 (rDer f2) has recently been developed as a promising allergen for the diagnosis and immunotherapy of house-dust mite allergy, and studies in immunology. The aim of the present study was to evaluate whether oral administration of rDer f2 could suppress an immediate allergic reaction in mice sensitized with mite allergen. We developed a murine allergic model that showed bronchoconstriction after inhalation of rDer f2, and studied the effect of oral administration of rDer f2 on the reaction.Seven week old male A/J mice were intranasally immunized with rDer f2 12 times. Sensitized mice showed anti-rDer f2 immunoglobulin (Ig)E production and immediate airway constriction after inhalation of 10 mg·mL -1 of rDer f2, as determined by the Konzett-Rössler method. Immunized animals were divided into three groups, and fed phosphate-buffered saline (PBS), 0.1 mg·day -1 , or 1 mg·day -1 of rDer f2 for 4 weeks, respectively. Seven days after the last feeding, the mice were examined for their immediate response.Animals fed with 1 mg·day -1 rDer f2 showed significantly reduced bronchoconstriction after inhalation of both 2 mg·mL -1 and 10 mg·mL -1 of rDer f2 compared with PBS-fed mice. Similar results were obtained when we examined mice 10 weeks after the last feeding. Reactions in the 0.1 mg·day -1 rDer f2-fed group also tended to decrease in comparison with PBS-fed animals. Plasma anti-rDer f2 IgE, IgG1, IgG2a, and IgG2b levels were not changed by feeding with rDer f2.We conclude that recombinant Der f2 exhibits both sensitizing and hyposensitizing activities in mice. rDer f2 may be useful in immunotherapy and diagnosis of housedust mite allergy. Eur Respir J 1998; 11: 144-150 To date, several clinically important allergens such as Der 1 and Der 2 have been identified in crude mite extract [1][2][3][4]. Among others, the structural gene of Der f2, one of the major mite allergens found in Dermatophagoides farinae was cloned, and the product (recombinant Der f2 (rDer f2)) shown to exhibit allergic activity in humans comparable with native Der f2 prepared from crude mite extract [5,6]. Since Der f2 has been shown to sensitize over 80% of patients with house-dust mite allergy, rDer f2 should prove useful in the diagnosis and immunotherapy of allergic asthma and rhinitis caused by house-dust mites. It should also provide a basis for research into allergies and immunology.In the present study, with special reference to the therapeutic application of rDer f2, we established a murine allergic model by intranasal or intraperitoneal injection of rDer f2 to A/J mice, which are highly responsive to Der f2 [7]. We examined the effect of oral-hyposensitization therapy with rDer f2 against the immediate bronchoconstriction in the intranasally sensitized animals because their reaction after rDer f2 inhalation was more intense than that of intraperitoneally immunized mice. Materials and methodsAntigen rDer f2, clone 1 [5], was kindly supplied by the Nikka Whisky Distilling Co., Ltd. (Chiba, Japan), and dissolved in...

Oral administration of allergen extracts from Dermatophagoides farinae desensitizes specific allergen-induced inflammation and airway hyperresponsiveness in rats

“…The Th1/ Th2 imbalance are correlated with the changes in serum total IgE and IgG, allergen-specific serum IgE and IgG levels, airway responsiveness and eosinophilia. Thus, in the present study, we suggested that AHR improvement is associated with a regulation in Th1/Th2 balance, a decrease in allergen-specific serum IgE and an increase in allergen-specific serum IgG in the allergic model of rats with oral immunotherapy, which is consistent with previous study, indicating that oral hyposensitization with recombinant Der f2 attenuates immediate airway constriction in a murine allergic model [22].…”

“…The conventionally used allergens include house mite allergen [19][20][21][22], pollen extract [23,24], ovalbumin [25] and peanut protein [26], Many studies showed that oral administration of allergen, including recombinant Derf2, effectively suppresses IgE responses in the allergic model of mice [19,20]. Although we supposed that the effects of Derfdrop is antigen-specific and it is not likely that Derfdrop affects immune response via antigen-non-specific way, it is still necessary to set up the experiments to verify the specificity of Derf allergen by using other allergen-induced asthmatic animal model.…”

Experimental Monkey Model Sensitized with Mite Antigen

“…Concerning a mite allergic model, Hsiue et al [4] recently reported the induction of allergic airway inflammation in guinea pigs that showed severe eosinophilia of the airway and immediate bronchoconstriction after intravenous injection of crude mite extract [4]. We have also developed murine allergic models exhibiting immediate airway constriction or neutrophil influx into the airway after antigen inhalation by using rDer f 2 as a sensitizing and provoking antigen [21,22]. However, no reports on the induction of anti-mite IgE in primates have been published to our knowledge.…”

Intranasal mite allergen induces allergic asthma-like responses in NC/Nga mice

“…Furthermore, most experimental allergic asthma models have been developed by systemic sensitization that involves either intraperitoneal or subcutaneous injection with adjuvants, such as aluminum hydroxide. Some investigators have developed mouse models of allergic airway eosinophilia (Ichinose et al, 2003;Sadakane et al, 2002;Yu et al, 1999), allergen-induced AHR (Herz et al, 1996), or allergen-induced airway obstruction (Yasue et al, 1998) using only local exposure of mite allergen without adjuvant. The intent of such models is to mimic the route of sensitization in humans as closely as possible.…”