Der p2 B细胞表位RNA疫苗制备及其对过敏性鼻炎小鼠特异性IgE抑制作用  

Preparation of a Der p2 B cell epitope RNA vaccine and its specific IgE inhibition in mice with allergic rhinitis

作　　者：杨贵[1] 胡田勇 贺海鹏 马莉 魏海峰 黄佳敏 刘志强 YANG Gui;HU Tianyong;HE Haipeng;MA Li;WEI Haifeng;HUANG Jiamin;LIU Zhiqiang(Shenzhen Longgang Central Hospital;Shenzhen Otolaryngology Institute/Longgang Otolaryngology Hospital,Shenzhen 518172,Guangdong,China)

机构地区：[1]深圳市龙岗中心医院 [2]深圳市龙岗区耳鼻咽喉医院/深圳市耳鼻咽喉研究所,广东深圳518172

出　　处：《山东大学耳鼻喉眼学报》2024年第5期6-12,共7页Journal of Otolaryngology and Ophthalmology of Shandong University

基　　金：国家自然科学基金资助项目(82371122,82071807);广东省自然科学基金资助项目(2022A1515012617);深圳市科技创新委员会(JCYJ20210324142207019);深圳市龙岗区科技发展专项资金(LGKCYLWS2023008,LGKCYLWS2023023,LGKCYLWS2022031)

摘　　要：目的尘螨过敏原Der p2 B细胞表位RNA疫苗的制备及其对过敏性鼻炎小鼠特异性IgE影响。方法经表位预测软件分析预测Der p2蛋白序列上B细胞表位肽,合成B细胞表位肽并进行体外IgE反应性分析,将B细胞表位肽与载体蛋白相连,构建B细胞表位RNA疫苗,RNA疫苗经脂质体包裹后,皮下注射给予过敏性鼻炎小鼠进行治疗,检测小鼠外周血特异性IgE、IgG4水平及Treg、Th17细胞变化。结果与Der p2阳性对照组相比,预测的四段B细胞表位肽均显示出低IgE反应性,差异具有统计学意义(P<0.001);与过敏性鼻炎组小鼠相比,经Der p2 B细胞表位RNA疫苗治疗后,血清特异性IgE水平明显下降,IgG4水平升高,差异具有统计学意义(P<0.05);同时,治疗后外周血中Treg比率有所增加,Th17比率降低,差异具有统计学意义(P<0.05)。结论成功构建了Der p2 B细胞表位RNA疫苗,并可有效降低过敏性鼻炎小鼠外周血特异性IgE,提高中和型抗体IgG4水平及Treg比率。Objective This study aimed to construct a house dust mite allergen Der p 2 B cell epitope RNA vaccine and evaluate its inhibitory potency against antigen-specific IgE in allergic rhinitis mice.Methods Epitope prediction software was utilized to predict potential B-cell epitope peptides on the Der p2 protein sequence,followed by synthesis of these peptides and analysis of their IgE reactivity in vitro.The B-cell epitope peptide was then linked with a carrier protein to construct the B-cell epitope RNA vaccine,which was administered to allergic rhinitis mice via subcutaneous injection.Levels of specific IgE,IgG4,Treg,and Th17 cells in the peripheral blood of the mice were subsequently tested.Results Compared with the recombinant Der p2 positive control group,the predicted four B cell epitope peptides exhibited significantly lower IgE reactivity(P<0.001).Furthermore,treatment with the Der p2 B cell epitope RNA vaccine led to a significant decrease in serum levels of specific IgE and an increase in IgG4 compared to mice in the allergic rhinitis group(P<0.05).Additionally,there was an increase in Treg ratio and a reduction in Th17 ratio after treatment(P<0.05).Conclusion The construction of the Der p2 B cell epitope RNA vaccine has been successfully achieved and it effectively reduces specific IgE levels while increasing neutralizing antibody levels and Treg ratios in peripheral blood of allergic rhinitis mice.

关 键 词：尘螨 B细胞表位 RNA疫苗 特异性IGE 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]