Research and Development, Stallergenes SA, Antony, France.
Clin Exp Allergy. 2011 Dec;41(12):1784-92. doi: 10.1111/j.1365-2222.2011.03865.x. Epub 2011 Sep 23.
Second generation therapeutic vaccines based upon recombinant allergens or natural extracts, potentially formulated in vector systems or adjuvants, are being developed. To this aim, preclinical studies in relevant animal models are needed to select proper allergens, formulations and administration schemes.
To develop a chronic house dust mite (HDM) allergy model to evaluate sublingual therapeutic vaccine candidates.
The BABL/c mice that were used were sensitized with Dermatophagoides pteronyssinus (Dpte) and Dermatophagoides farinae (Dfar) mite extracts by intraperitoneal injections followed by aerosol exposures. Animals subsequently underwent sublingual immunotherapy (SLIT) with either Dpte, Dfar or Dpte/Dfar extracts, twice a week for 8 weeks. SLIT efficacy was assessed by whole body plethysmography, lung histology and broncho-alveolar lavages cell counts. Specific T cell and antibody responses to major and minor HDM allergens were monitored in tissues and serum/saliva, respectively.
Mice sensitized to Dpte and Dfar allergens exhibited strong airway hyperresponsiveness (AHR) and lung inflammatory infiltrates including eosinophils. Sensitized animals mounted Th2-biased cellular and humoral responses specific for group 1 and 2 major allergens, as well as group 5, 7 and 10 minor allergens. This phenotype was sustained for at least 2 months, allowing the evaluation of immunotherapeutic protocols with HDM extracts-based vaccines. In this model, SLIT decreased AHR and Th2 responses and induced HDM-specific IgAs in saliva. The Dpte/Dfar mix proved the most efficacious when compared to Dpte or Dfar extracts alone.
The efficacy of a sublingual vaccine based on a Dpte/Dfar allergen extract mix was demonstrated in a well standardized murine model of chronic allergic airway inflammation based on clinically relevant mite allergens. The latter will be used as a benchmark for evaluation of future vaccines, including recombinant allergens. This HDM allergic airway inflammation animal model is a useful tool to design and select candidate vaccines to be tested in humans.
基于重组过敏原或天然提取物的第二代治疗性疫苗，可能在载体系统或佐剂中进行配制，正在开发中。为此，需要在相关动物模型中进行临床前研究，以选择合适的过敏原、配方和给药方案。
建立慢性屋尘螨（HDM）过敏模型，以评估舌下治疗性疫苗候选物。
使用 BABL/c 小鼠，通过腹腔注射和雾化暴露，用屋尘螨（Dpte）和粉尘螨（Dfar）螨提取物进行致敏。随后，动物接受 Dpte、Dfar 或 Dpte/Dfar 提取物的舌下免疫治疗（SLIT），每周两次，共 8 周。通过全身 plethysmography、肺组织学和支气管肺泡灌洗细胞计数评估 SLIT 的疗效。分别在组织和血清/唾液中监测主要和次要 HDM 过敏原的特异性 T 细胞和抗体反应。
对 Dpte 和 Dfar 过敏原敏感的小鼠表现出强烈的气道高反应性（AHR）和肺炎症浸润，包括嗜酸性粒细胞。致敏动物产生针对第 1 组和第 2 组主要过敏原以及第 5、7 和 10 组次要过敏原的 Th2 偏向细胞和体液反应。这种表型至少持续 2 个月，允许评估基于 HDM 提取物的疫苗的免疫治疗方案。在该模型中，SLIT 降低了 AHR 和 Th2 反应，并诱导了唾液中的 HDM 特异性 IgA。与单独使用 Dpte 或 Dfar 提取物相比，Dpte/Dfar 混合物证明更有效。
在基于临床相关螨过敏原的慢性过敏性气道炎症的标准化小鼠模型中，证明了基于 Dpte/Dfar 过敏原提取物混合物的舌下疫苗的疗效。后者将作为评估未来疫苗的基准，包括重组过敏原。这种 HDM 过敏性气道炎症动物模型是设计和选择候选疫苗以在人类中进行测试的有用工具。
