Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine.
Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine.
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DOI：
10.1371/journal.pone.0150463
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sookrung N
中科院分区：
文献类型：
--
作者：
Tasaniyananda N;Chaisri U;Tungtrongchitr A;Chaicumpa W;Sookrung N
猫(猫科动物)是空气传播过敏原的丰富来源，在环境中盛行，并使许多人对过敏敏感。本研究首次建立了猫变应原所致变应性鼻炎的小鼠模型，并以猫毛粗提物(CCE)为对照，研究了以天然猫毛变应原FEL-1为主要变应原制成的新型脂质体鼻腔疫苗的治疗效果。用CCE和明矾混合溶液对BALB/c小鼠进行腹腔和鼻腔致敏。过敏性小鼠每隔一天给予8剂脂质体(L)包裹的天然FEL-1(L-nFD1，L-CCE)或安慰剂治疗。在气雾性CCE处理组小鼠激发后1天进行疫苗效力评价。所有过敏性小鼠均出现变应性鼻炎的组织学特征，血清特异性IgE和Th2细胞因子基因表达升高。与安慰剂组小鼠相比，免疫后过敏小鼠的血清IgE和鼻腔粘液产量显著减少。疫苗还导致Th2型反应(Th2型细胞因子表达减少)转向非致病反应：Th1(下调Th1抑制细胞因子基因IL-35)和Treg(上调IL-10和转化生长因子β)。综上所述，成功建立了猫变应原致变应性鼻炎小鼠模型。鼻腔、脂质体佐剂疫苗，特别是精制的单一变应原配方，缓解了模型小鼠的过敏表现。该原型疫苗值得在宠物过敏患者的临床应用中进一步试验。
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.