Aliu Have, Rask Carola, Brimnes Jens, Andresen Thomas Lars
Immunology Department, In vivo Biology Team, ALK Abelló A/S, Hørsholm.
Department of Micro- and Nanotechnology, Technical University of Denmark.
Int J Nanomedicine. 2017 Nov 22;12:8377-8388. doi: 10.2147/IJN.S137033. eCollection 2017.
Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model. We investigated the liposome carriers' ability to improve tolerance induction of antigens compared to the corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice sublingually treated with OVA-liposomes showed a significant reduction of airway eosinophilia and splenocyte proliferation in comparison to free OVA. A similar nonsignificant pattern was seen for OVA-specific IgE antibodies. In addition, reduced levels of interferon-γ and interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome-treated mice compared to the sham-treated group. In conclusion, in vivo efficacy data showed that prophylactic SLIT with OVA-liposomes is significantly more effective in preventing allergic inflammation than the corresponding dose of free OVA.
通过舌下给予变应原进行免疫疗法具有较高的患者依从性,已成为皮下免疫疗法治疗IgE相关过敏性疾病的替代方法。然而,舌下免疫疗法(SLIT)可能会引起不良事件。开发能够实现更高效递送从而降低变应原负荷的变应原递送系统可能会减少不良事件。在本研究中,我们在卵清蛋白(OVA)诱导的过敏性气道炎症模型中,研究了中性和阳离子脂质体作为模型变应原OVA的递送系统。我们研究了与相应剂量的游离OVA相比,脂质体载体提高抗原耐受诱导的能力。小鼠在2周内舌下给予游离或脂质体包裹的OVA,随后进行腹腔注射和鼻内激发。与游离OVA相比,用OVA-脂质体舌下治疗的小鼠气道嗜酸性粒细胞增多和脾细胞增殖显著减少。OVA特异性IgE抗体也呈现出类似的不显著模式。此外,与假处理组相比,在OVA-脂质体处理的小鼠的脾细胞培养上清液中观察到干扰素-γ和白细胞介素-5水平降低。总之,体内疗效数据表明,用OVA-脂质体进行预防性SLIT在预防过敏性炎症方面比相应剂量的游离OVA显著更有效。