摘要
目的以一种CpG寡聚核苷酸为HIV-1DNA疫苗候选佐剂,研究该CpG佐剂增强DNA疫苗免疫原性,体外促进DC细胞成熟等特点。方法在Balb/c小鼠模型上连续3次联合免疫HIV-1DNA疫苗及CpG佐剂,通过IFN-γ、IL-2ELISPOT及ELISA检测HIV特异性细胞免疫反应及体液免疫应答强度;体外制备小鼠骨髓来源的树突状细胞,通过FACS技术、高通量细胞因子检测等方法评价CpG佐剂刺激活化DC的能力。结果 CpG能够增强HIV-1DNA疫苗诱导的特异性细胞免疫反应水平,降低DNA疫苗使用剂量;CpG体外刺激原代小鼠骨髓来源的树突状细胞(BMDC),能显著上调CD40、CD80、CD86等BMDC表面共刺激分子的表达,活化BMDC并分泌各型细胞因子IL-5、IL-12p70,促炎症因子IL-1α、IL-1β、IL-6、IL-10、MIP-2、KC、MIG、Eotaxin、GM-CSF等以发挥佐剂效应。结论综合体内体外实验数据,证实该型CpG能够充分活化BMDC,显著提高HIV-1DNA疫苗免疫原性,降低疫苗使用剂量,可成为HIV-1DNA疫苗临床试验用候选佐剂。
Objective To explore the capacity of CpG as adjuvant in improving HIV-1 DNA vaccine immunogenicity in animal models.Methods Balb/c mice were administrated thrice intramuscularly with CpG oligonucleotide adjuvanted HIV-1 DNA vaccine,pDRVI1.0-gp1455m.Cellular immune response was evaluated by detecting IFN-γ and IL-2 with ELISPOT.Humoral immune response was evaluated with Env-specific ELISA and avidity ELISA.The activation efficacy of bone marrow-derived dendritic cells（BMDC） was measured by the expression of surface molecules and the secretion of several cytokines after being exposed to CpG adjuvant in vitro.Results The results demonstrated that CpG increased HIV specific cellular response and reduced the dosage of DNA vaccine.In vitro,CpG adjuvant activated BMDC and up-regulated the expression of CD40,CD80,CD86 and MHC-I.CpG adjuvanted HIV DNA vaccine also promoted Th1-type immunological response and induced inflammation.Conclusion CpG is a promising adjuvant for the development of HIV DNA vaccine.
出处
《中国预防医学杂志》
CAS
2011年第12期979-984,共6页
Chinese Preventive Medicine
基金
国家科技重大专项项目创新性复制非复制载体艾滋病疫苗研究(2008ZX1001-1010)
