摘要
目的初步探讨新型生物佐剂BC01(BCG CpG DNA compound adjuvant system 01)对机体的免疫激活作用。方法将C57BL/6小鼠随机分为4组并分别肌肉注射75μg新型生物佐剂BC01,实验组于免疫后6、12和24 h解剖取脾脏,对照组于注射BC01后0 h解剖取脾脏。提取各组小鼠总RNA并进行全基因转录组分析。基因芯片数据经归一化处理后进行基因集富集分析(gene set enrichment analysis,GSEA)。同时,采用实时定量PCR法对GSEA中GO(gene ontology,GO)基因集分组归类中生物过程(biological process,BP)、细胞成分(cellular component,CC)和分子功能(molecular function,MF)相关上调基因进行验证分析。结果小鼠全基因转录组芯片数据经GSEA分析后发现,BC01佐剂具有活化免疫细胞,激活固有免疫和适应性免疫应答,调节炎症反应、活化免疫细胞迁移与趋化,激活免疫细胞吞噬功能以及促分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)和细胞外调节蛋白激酶1/2(extracellular-regulated kinase 1/2,ERK1/2)信号级联反应作用。结论新型生物佐剂BC01经肌肉注射24 h后具有较强的机体免疫激活作用。
Objective To preliminarily investigate the immune activation effect of novel biological adjuvant BC01(BCG CpG DNA compound adjuvants system 01)in mice.Methods C57BL/6 mice were randomly divided into four groups and injected i.m.with 75μg of novel biological adjuvant BC01.The spleens of mice in three test groups were collected 6,12 and 24 h,while those in control group 0 h,after immunization,from which total RNAs were extracted and subjected to whole-genome transcriptome gene chip analysis.The gene chip data were normalized and then subjected to gene set enrichment analysis(GSEA).Meanwhile,real-time quantitative PCR was used to verify and analyze the up-regulated genes related to the biological process(BP),cellular component(CC)and molecular function(MF)in the grouping and classification of gene ontology(GO)gene sets under GSEA.Results GSEA of gene chip data showed that BC01 adjuvant activated the immune cells as well as innate immunity and adaptive immune response,regulated inflammatory reaction,activated the migration and chemotaxis of immune cells,immune cell phagocytosis,the signal cascade reaction of mitogen-activated protein kinase(MAPK)and extracellular-regulated kinase 1/2(ERK1/2).Conclusion The novel biological adjuvant BC01 showed a strong immune activation effect 24 h after intramuscular injection.
作者
李军丽
付丽丽
杨阳
王国治
赵爱华
LI Jun-li;FU Li-li;YANG Yang;WANG Guo-zhi;ZHAO Ai-hua(Division of Tuberculosis Vaccine and Allergen Products,National Institutes for Food and Drug Control,Beijing 102629,China)
出处
《中国生物制品学杂志》
CAS
CSCD
北大核心
2022年第8期928-936,942,共10页
Chinese Journal of Biologicals
基金
2020年北京市自然科学基金-海淀原始创新联合基金项目(L202040).
