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Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine

机译:猫过敏性鼻炎和鼻内脂质体佐剂的精制Fel d 1疫苗的小鼠模型

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摘要

Cats (Felis domesticus) are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen) in comparison with the vaccine made of crude cat hair extract (cCE). BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L)-entrapped native Fel d 1 (L-nFD1), L-cCE), or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions) towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35) and Treg (up-regulation of IL-10 and TGF-β). In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients.
机译:猫(Felis domesticus)是空气中过敏原的丰富来源,这些物质在环境中普遍存在,并使许多人对过敏敏感。在这项研究中,首次开发了由猫过敏原引起的过敏性鼻炎的小鼠模型,该模型用于测试由天然Fel d 1(主要猫过敏原)制成的新型鼻腔脂质体包裹疫苗的治疗效果。与粗猫毛提取物(cCE)制成的疫苗进行比较。 BALB / c小鼠经腹膜内和鼻内混有明矾的cCE致敏。每隔一天用八剂脂质体(L)包裹的天然Fel d 1(L-nFD1),L-cCE)或安慰剂治疗过敏性小鼠。在用气溶胶性cCE激发治疗的小鼠后一天进行疫苗功效评估。所有变态反应的小鼠都发展了变应性鼻炎的组织学特征,其血清特异性IgE和Th2细胞因子基因表达也随之增加。与安慰剂小鼠相比,接种疫苗后变态反应小鼠的血清IgE和鼻内粘液产生显着降低。疫苗还引起Th2反应(Th2细胞因子表达的减少)向非致病反应的转移:Th1(Th1抑制性细胞因子基因的下调,IL-35)和Treg(IL-10的上调)和TGF-β)。结论是,成功开发了猫过敏原的变应性鼻炎小鼠模型。鼻内脂质体佐剂疫苗,尤其是精制的单一过敏原制剂,减轻了模型小鼠的过敏表现。原型疫苗值得进一步测试以用于宠物过敏患者的临床。

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