Calzada D, Aranda T, M Gallego G, Escutia M R, Balsa D, Álvarez J, Mayorga C, Salas M, Odena M A, Oliveira E, Pascal M, Carnés J
R&D Allergy & Immunology Unit, LETI Pharma, Madrid, Spain.
Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain; Allergy Clinical Unit, Hospital Regional Universitario de Málaga, Málaga, Spain.
Mol Immunol. 2022 May;145:88-96. doi: 10.1016/j.molimm.2022.02.020. Epub 2022 Mar 17.
Dog allergens are a common cause of allergic sensitisation and trigger respiratory symptoms worldwide. However, clinical evidence regarding dog immunotherapy is limited. Therefore, the aim of this study was to analyse the immunomodulatory properties of a new allergoid from dog dander, thereby deepening the understanding of the molecular mechanisms involved in the reestablishment of the tolerogenic response.
Three independent batches of dog dander native and allergoid allergen extracts were manufactured and characterised. Allergenic profiles were analysed by the identification of all dog allergens and quantification of the major allergens Can f 1 and Can f 5. The allergenicity profile of the allergoid was studied using biological potency and basophil activation tests. In vitro immunomodulatory parameters was evaluated as the capacity of the allergoid to induce IgG antibodies that block IgE binding to the allergen and cytokine promotion (IFN-γ, IL-4, IL-6, IL-10, IL-13, and TNF-α) in PBMCs from allergic donors.
The presence of all dog allergens, including Can f 1 and Can f 5, was confirmed in both types of extracts. The new allergoid showed a low IgE binding capacity, which significantly affected the activation of effector cells, such as basophils. The IgG antibodies induced by the allergoid in rabbits blocked human IgE binding epitopes on the dog native extract and induced Th1 and Treg responses by increasing IFN-γ and IL-10 levels in PBMCs from allergic donors.
This new dog dander allergoid containing Can f 1 and Can f 5 showed a low capacity to bind IgE and to activate basophils in dog allergic patients. Furthermore, it showed potent activation of Th1 mediators and induction of tolerance through Treg activation. This allergoid could offer a safer profile than the native extract and could be an effective immunotherapy treatment for dog allergic patients.
犬过敏原是全球范围内引起过敏致敏和引发呼吸道症状的常见原因。然而，关于犬免疫疗法的临床证据有限。因此，本研究的目的是分析一种来自犬皮屑的新型变应原疫苗的免疫调节特性，从而加深对参与重建耐受反应的分子机制的理解。
制备并表征了三批独立的犬皮屑天然和变应原疫苗过敏原提取物。通过鉴定所有犬过敏原并定量主要过敏原Can f 1和Can f 5来分析过敏原谱。使用生物活性和嗜碱性粒细胞活化试验研究变应原疫苗的过敏原性谱。体外免疫调节参数评估为变应原疫苗诱导IgG抗体阻断IgE与过敏原结合的能力以及在过敏供体的外周血单核细胞中促进细胞因子（IFN-γ、IL-4、IL-6、IL-10、IL-13和TNF-α）的能力。
在两种提取物中均证实了所有犬过敏原的存在，包括Can f 1和Can f 5。新型变应原疫苗显示出低IgE结合能力，这显著影响了效应细胞如嗜碱性粒细胞的活化。变应原疫苗在兔体内诱导的IgG抗体阻断了犬天然提取物上的人IgE结合表位，并通过增加过敏供体外周血单核细胞中IFN-γ和IL-10水平诱导Th1和调节性T细胞反应。
这种含有Can f 1和Can f 5的新型犬皮屑变应原疫苗在犬过敏患者中显示出低IgE结合能力和嗜碱性粒细胞活化能力。此外，它显示出Th1介质的有效活化和通过调节性T细胞活化诱导耐受。这种变应原疫苗可能比天然提取物具有更安全的特性，并且可能是犬过敏患者的一种有效免疫治疗方法。
