Scalise Melanie Cristine, Mutlu Seyran, Ferrié Céline, Amacker Mario, von Garnier Christophe, Stumbles Philip, Blank Fabian
Lung Precision Medicine (LPM), Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Front Allergy. 2025 Aug 29;6:1633293. doi: 10.3389/falgy.2025.1633293. eCollection 2025.
Allergic asthma is characterized by airway hyperresponsiveness due to a biased Th2 immune response against harmless environmental substances. While most current treatments alleviate symptoms without altering the disease's progression, allergen-specific immunotherapy (AIT) is the only clinically approved strategy known to modify the natural course of allergic disease. However, AIT has limitations, highlighting the need for improved formulations that provide safer, faster, and more effective immune modulation.
In this study, we designed bio-mimetic nanoparticles and evaluated their effects in a mouse model of experimental allergic inflammatory airways disease (EAIAD). Mice were sensitized with ovalbumin (OVA) and treated with liposomes or virosomes conjugated with OVA and the TLR7/8 agonist 3M-052. Lung function, inflammatory cell recruitment, cytokine profiles, and immunoglobulin levels were analyzed post-treatment.
Among the tested formulations, liposomes co-delivering OVA and 3M-052 (Lipo-OVA) led to partial improvements in lung mechanics, including lower airway resistance (Rrs) and preserved forced expiratory volume (FEV0.1). Immune profiling revealed formulation-specific effects on eosinophil and macrophage populations, and modest shifts in cytokine secretion patterns. However, no formulation fully resolved airway inflammation or significantly reduced Th2 cytokines or total IgE levels.
These findings support the feasibility of nanoparticle-based AIT strategies, while also highlighting the need for further optimization to enhance efficacy, minimize sensitization, and promote sustained long-term immune tolerance.
过敏性哮喘的特征是由于针对无害环境物质的偏向性Th2免疫反应导致气道高反应性。虽然目前大多数治疗方法可缓解症状但不改变疾病进展，而变应原特异性免疫疗法（AIT）是唯一已知可改变过敏性疾病自然病程的临床批准策略。然而，AIT存在局限性，这凸显了对改进制剂的需求，以提供更安全、更快且更有效的免疫调节。
在本研究中，我们设计了仿生纳米颗粒，并在实验性过敏性炎症气道疾病（EAIAD）小鼠模型中评估了它们的效果。用卵清蛋白（OVA）使小鼠致敏，并用与OVA和TLR7/8激动剂3M-052偶联的脂质体或病毒体进行治疗。治疗后分析肺功能、炎症细胞募集、细胞因子谱和免疫球蛋白水平。
在测试的制剂中，共同递送OVA和3M-052的脂质体（Lipo-OVA）使肺力学有部分改善，包括较低的气道阻力（Rrs）和保留的用力呼气量（FEV0.1）。免疫分析揭示了制剂对嗜酸性粒细胞和巨噬细胞群体的特异性作用，以及细胞因子分泌模式的适度变化。然而，没有一种制剂能完全解决气道炎症或显著降低Th2细胞因子或总IgE水平。
这些发现支持基于纳米颗粒的AIT策略的可行性，同时也凸显了进一步优化以提高疗效、最小化致敏并促进持续长期免疫耐受的必要性。
