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本研究在前期工作基础上,用CHO细胞表达的含PreS1+S融合抗原的新型基因工程HBV颗粒疫苗(HBSS1)与Al(OH)3、CpG及CpG+Al(OH)3等佐剂配伍,在Balb/C小鼠模型上研究不同佐剂对HBV颗粒疫苗肌肉注射后免疫应答的影响,主要包括抗体滴度、抗体亚型分类及特异性细胞免疫(γ-IFNELISpot检测)。结果表明:CpG佐剂结合HBSS1颗粒疫苗可快速诱导(单针免疫)高水平的抗PreS1及S抗体,IgG2a/IgG1比率>1,同时可诱导较高抗原特异的细胞免疫应答;Al(OH)3+CpG双佐剂组一次免疫后可诱导产生最高的抗S抗体滴度(1:105),其产生的抗体亚类包括IgG1、IgG2a与IgG2b;在S抗原N端(13~49aa)存在优势CTL表位。结论:CpG佐剂结合HBSS1颗粒疫苗应是发展新型治疗性乙肝疫苗的较佳选项。
In this study, based on the previous work, a novel genetically engineered HBV particle vaccine (HBSS1) containing PreS1 + S fusion antigen expressed in CHO cells was used in combination with adjuvants such as Al (OH) 3, CpG and CpG + Al (OH) The effects of different adjuvants on the immune response of HBV granule vaccine after intramuscular injection were studied in Balb / C mice model, including antibody titers, antibody subtypes classification and specific cellular immunity (γ-IFNELISpot test). The results showed that: CpG adjuvant combined with HBSS1 particle vaccine can rapidly induce high level of anti-PreS1 and S antibodies (single-needle immunization), IgG2a / IgG1 ratio> 1 and induce higher antigen-specific cellular immune response; The highest anti-S antibody titers (1: 105) were induced after one immunization with 3 + CpG double adjuvant. The antibody subtypes produced include IgG1, IgG2a and IgG2b; in the N terminus of S antigen (13-49aa) Advantageous CTL epitopes. Conclusion: CpG adjuvant combined with HBSS1 particle vaccine should be a better option for developing novel therapeutic hepatitis B vaccine.