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蛋自序列上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.
Abstract
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 re-activity 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 Th 17 cells in the pe-ripheral 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 treat-ment(P＜0.05).Conclusion The construction of the Der p2 B cell epitope RNA vaccine has been successfully achieved and it ef-fectively reduces specific IgE levels while increasing neutralizing antibody levels and Treg ratios in peripheral blood of allergic rhini-tis mice.
基金项目
国家自然科学基金资助项目(82371122)
国家自然科学基金资助项目(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)
深圳市龙岗区科技发展专项资金(LGKCYLWS2023023)
深圳市龙岗区科技发展专项资金(LGKCYLWS2022031)
NETL
NSTL
万方数据