Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Allergy. 2019 Mar;74(3):572-582. doi: 10.1111/all.13659. Epub 2018 Nov 25.
Insect-bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type-I/type-IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin-5 (IL-5) is the key cytokine for eosinophils and we have previously shown that targeting IL-5 by vaccination reduces disease symptoms in horses.
Here, we analyzed the potential for long-term therapy by assessing a second follow-up year of the previously published study.
The vaccine consisted of equine IL-5 (eIL-5) covalently linked to a cucumber mosaic virus-like particle (VLP) containing a universal T cell epitope (CuMV ) using a semi-crossover design to follow vaccinated horses during a second treatment season. Thirty Icelandic horses were immunized with 300 μg of eIL-5-CuMV without adjuvant.
The vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti-eIL-5 auto-antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms.
Yearly vaccination against IL-5 may be a long-term solution for the treatment of IBH and other eosinophil-mediated diseases in horses and other species including humans.
昆虫叮咬超敏反应(IBH)是一种由昆虫叮咬引起的慢性过敏性皮炎。马患有瘙痒性皮肤病变,由 I 型/IV 型过敏反应引起,伴有明显的嗜酸性粒细胞浸润到皮肤中。白细胞介素-5(IL-5)是嗜酸性粒细胞的关键细胞因子,我们之前已经表明,通过接种疫苗靶向 IL-5 可以减轻马的疾病症状。
通过评估之前发表的研究的第二个随访年来分析长期治疗的潜力。
疫苗由与黄瓜花叶病毒样颗粒(CuMV)共价连接的马白细胞介素-5(eIL-5)组成,该颗粒含有通用 T 细胞表位(CuMV),使用半交叉设计来随访接种疫苗的马在第二个治疗季节。30 匹冰岛马用 300μg 的 eIL-5-CuMV 无佐剂进行免疫接种。
疫苗耐受性良好,整个研究过程中未发现任何安全问题。接种疫苗后,所有马都产生了可逆的抗 eIL-5 自身抗体滴度。与安慰剂治疗相比,嗜酸性粒细胞水平的平均病程降低,导致临床病变评分显著降低。与第一年治疗相比,第二年接种疫苗的马的疾病症状改善更为明显,这可能是由于单次加强注射诱导更稳定的抗体滴度所致。因此,反应可以维持两个季节,马仍然可以免受疾病症状的影响。
每年接种针对 IL-5 的疫苗可能是治疗 IBH 和其他马以及包括人类在内的其他物种中嗜酸性粒细胞介导疾病的长期解决方案。