Center of Allergy and Environment (ZAUM), Technical University of Munich, Faculty of Medicine and Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center of Lung Research (DZL), Member of the Immunology and Inflammation Initiative of the Helmholtz Association, Munich, Germany.
Department of Otolaryngology, Klinikum rechts der Isar, Faculty of Medicine, Technical University of Munich, Munich, Germany.
Allergy. 2022 Mar;77(3):907-919. doi: 10.1111/all.15012. Epub 2021 Jul 26.
Native allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen-specific immunotherapy (AIT), although mechanistic side-by-side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively. In this study, immunological effects of experimental house dust mite (HDM) AIT were investigated applying high-dose HDM extract and low-dose HDM allergoids with and without the adjuvants microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) in a murine model of HDM allergy.
Cellular, humoral, and clinical effects of the different AIT strategies were assessed applying a new experimental AIT model of murine allergic asthma based on physiological, adjuvant-free intranasal sensitization followed by subcutaneous AIT.
While low-dose allergoid and high-dose extract AIT demonstrated comparable potency to suppress allergic airway inflammation and Th2-type cytokine secretion of lung-resident lymphocytes and draining lymph node cells, low-dose allergoid AIT was less effective in inducing a potentially protective IgG1 response. Combining low-dose allergoid AIT with MCT or MCT and dose-adjusted MPL promoted Th1-inducing mechanisms and robust B-cell activation counterbalancing the allergic Th2 immune response.
Low allergen doses induce cellular and humoral mechanisms counteracting Th2-driven inflammation by using allergoids and dose-adjusted adjuvants. In light of safety and efficacy improvement, future therapeutic approaches may use low-dose allergoid strategies to drive cellular tolerance and adjuvants to modulate humoral responses.
天然过敏原提取物或化学修饰的变应原经常用于诱导过敏原特异性免疫疗法（AIT）中的过敏原耐受，尽管很少有机制方面的平行研究。平衡最佳剂量和变应原性以实现安全保证的疗效至关重要。通过降低过敏原剂量和/或使用变应原和免疫刺激性佐剂，可以分别解决 AIT 的安全性和疗效问题。在这项研究中，应用高剂量屋尘螨（HDM）提取物和低剂量 HDM 变应原，并分别使用佐剂微结晶酪氨酸（MCT）和单磷酰脂质 A（MPL），在 HDM 过敏的小鼠模型中研究了实验性 HDM AIT 的免疫学效应。
应用新的基于生理的、无佐剂的鼻腔致敏后皮下 AIT 的小鼠变应性哮喘实验性 AIT 模型，评估了不同 AIT 策略的细胞、体液和临床效应。
低剂量变应原和高剂量提取物 AIT 均具有抑制过敏性气道炎症和肺驻留淋巴细胞和引流淋巴结细胞 Th2 型细胞因子分泌的相当效力，而低剂量变应原 AIT 在诱导潜在保护性 IgG1 反应方面效果较差。低剂量变应原 AIT 与 MCT 或 MCT 和剂量调整的 MPL 联合使用可促进 Th1 诱导机制和强大的 B 细胞激活，从而抵消过敏的 Th2 免疫反应。
低过敏原剂量通过使用变应原和剂量调整的佐剂诱导细胞和体液机制来对抗 Th2 驱动的炎症。鉴于安全性和疗效的改善，未来的治疗方法可能会使用低剂量变应原策略来驱动细胞耐受，使用佐剂来调节体液反应。
