Utsumi Daichi, Suzuki Keisuke, Matsuhara Hiroki, Kuroda Etsushi, Ishii Ken J, Ohashi-Doi Katsuyo
Innovation Research Laboratory, Torii Nihonbashi Bldg., 3-4-1 Nihonbashi-Honcho, Chuo-ku, Tokyo 103-8439, Japan.
Department of Immunology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Biol Pharm Bull. 2025;48(8):1191-1198. doi: 10.1248/bpb.b25-00138.
Allergy immunotherapy (AIT) plays a pivotal role in the treatment of type I allergic conditions such as allergic rhinitis and rhinoconjunctivitis. However, AIT faces persistent issues, notably the risk of anaphylaxis and the need for long-term treatment. To address these issues, various strategies have been explored, including the use of adjuvants, allergen delivery systems, and allergen modifications. This study used a prophylactic mouse model of allergic sensitization to explore the potential for improving the efficacy and safety of Japanese cedar pollen (JCP) subcutaneous immunotherapy (SCIT). In this model, JCP extract was combined with an adjuvant (K3 CpG oligodeoxynucleotide [CpG-ODN]) and/or a delivery system (dilauroyl phosphatidylcholine/deoxycholic acid [DLPC/DA] micelles) for subcutaneous immunization of naïve mice. Compared to immunization with JCP alone, the combination of JCP with K3 CpG-ODN and DLPC/DA micelles resulted in a general reduction of the JCP-induced T-helper 2 (Th2) immune response, including reduced airway inflammation and allergen-specific plasma immunoglobulin E. In addition, Th1 markers were either largely unaffected (interferon-γ) or markedly increased (allergen-specific plasma IgG2a). These immunological changes coincided with reduced sneezing frequency in response to allergen exposure. For most parameters, a synergistic effect was observed when both K3 CpG-ODN and DLPC/DA micelles were combined with JCP at the time of immunization. In conclusion, the data presented here indicate that the combination of JCP, K3 CpG-ODN, and DLPC/DA micelles is a promising candidate for the development of a more effective SCIT treatment for Japanese cedar pollinosis, which may include a shorter treatment regimen and reduced risk of anaphylactic reactions.
变应性免疫疗法（AIT）在治疗I型变态反应性疾病如变应性鼻炎和鼻结膜炎中起着关键作用。然而，AIT面临着一些长期存在的问题，尤其是过敏反应的风险以及长期治疗的必要性。为了解决这些问题，人们探索了各种策略，包括使用佐剂、变应原递送系统和变应原修饰。本研究使用变应性致敏的预防性小鼠模型，探讨改善日本雪松花粉（JCP）皮下免疫疗法（SCIT）疗效和安全性的潜力。在该模型中，将JCP提取物与佐剂（K3 CpG寡脱氧核苷酸 [CpG-ODN]）和/或递送系统（二月桂酰磷脂酰胆碱/脱氧胆酸 [DLPC/DA] 胶束）联合，对未致敏小鼠进行皮下免疫。与单独使用JCP免疫相比，JCP与K3 CpG-ODN和DLPC/DA胶束联合使用可使JCP诱导的辅助性T细胞2（Th2）免疫反应普遍降低，包括气道炎症减轻和变应原特异性血浆免疫球蛋白E减少。此外，Th1标志物要么基本未受影响（干扰素-γ），要么显著增加（变应原特异性血浆IgG2a）。这些免疫变化与变应原暴露后打喷嚏频率降低相一致。对于大多数参数，在免疫时将K3 CpG-ODN和DLPC/DA胶束与JCP联合使用时观察到协同效应。总之，此处呈现的数据表明，JCP、K3 CpG-ODN和DLPC/DA胶束的联合是开发更有效的日本雪松花粉症SCIT治疗方法的有前景的候选方案，该方法可能包括更短的治疗方案和降低过敏反应的风险。
