Fukuda Ken, Ishida Waka, Harada Yosuke, Wakasa Yuhya, Takagi Hidenori, Takaiwa Fumio, Fukushima Atsuki
Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi, Japan.
Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi, Japan.
Allergol Int. 2018 Jan;67(1):119-123. doi: 10.1016/j.alit.2017.06.006. Epub 2017 Jul 1.
We have previously shown that prophylactic oral administration of transgenic rice seeds expressing hypoallergenic modified antigens suppressed the development of allergic conjunctivitis induced by Japanese cedar pollen. We have now investigated the efficacy of oral immunotherapy with such transgenic rice for established allergic conjunctivitis in mice.
BALB/c mice were sensitized with two intraperitoneal injections of Japanese cedar pollen in alum, challenged with pollen in eyedrops, and then fed for 16 days with transgenic rice seeds expressing modified Japanese cedar pollen allergens Cry j 1 and Cry j 2 or with nontransgenic rice seeds as a control. They were then challenged twice with pollen in eyedrops, with clinical signs being evaluated at 15 min after the first challenge and the eyes, blood, spleen, and lymph nodes being isolated at 24 h after the second challenge.
The number of eosinophils in the conjunctiva and the clinical score for conjunctivitis were both significantly lower in mice fed the transgenic rice than in those fed nontransgenic rice. Oral vaccination with transgenic rice seeds also resulted in a significant increase in the production of IFN-γ by splenocytes, whereas it had no effect on the number of CD4CD25Foxp3 regulatory T cells in the spleen or submandibular or mesenteric lymph nodes.
Oral administration of transgenic rice seeds expressing hypoallergenic allergens ameliorated allergic conjunctivitis in the established setting. Such a rice-based edible vaccine is potentially both safe and effective for oral immunotherapy in individuals with allergic conjunctivitis.
我们之前已经表明,预防性口服表达低变应原性修饰抗原的转基因水稻种子可抑制日本柳杉花粉诱导的过敏性结膜炎的发展。我们现在研究了这种转基因水稻口服免疫疗法对小鼠已建立的过敏性结膜炎的疗效。
用两次腹腔注射含明矾的日本柳杉花粉使BALB/c小鼠致敏,用眼药水滴注花粉进行激发,然后用表达修饰的日本柳杉花粉变应原Cry j 1和Cry j 2的转基因水稻种子或用非转基因水稻种子作为对照喂养16天。然后用眼药水对它们进行两次花粉激发,在第一次激发后15分钟评估临床症状,并在第二次激发后24小时分离眼睛、血液、脾脏和淋巴结。
喂食转基因水稻的小鼠结膜中的嗜酸性粒细胞数量和结膜炎的临床评分均显著低于喂食非转基因水稻的小鼠。用转基因水稻种子进行口服疫苗接种还导致脾细胞产生IFN-γ显著增加,而对脾脏、下颌下或肠系膜淋巴结中CD4CD25Foxp3调节性T细胞的数量没有影响。
口服表达低变应原性变应原的转基因水稻种子可改善已建立的过敏性结膜炎。这种基于水稻的可食用疫苗对过敏性结膜炎患者的口服免疫疗法可能既安全又有效。