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为研制新型有效的HBV治疗性疫苗,构建了含PreS1与S融合基因的HBV DNA疫苗,即pVRC-HBSS1(PreS121–47 aa融合在S抗原1–223 aa的羧基端),并制备了CHO表达相同结构的蛋白颗粒亚单位疫苗HBSS1。在Balb/C小鼠中采用不同的DNA免疫方式(即肌肉注射、皮内注射加电转)初免3次,蛋白颗粒亚单位疫苗(不同佐剂)肌肉注射加强免疫1次,然后我们分析比较了各组疫苗所引起的免疫应答特点。抗体检测结果表明:皮内注射结合电转初免组产生的PreS1与S特异性抗体水平皆高于肌肉直接注射组。进一步还发现DNA疫苗与蛋白颗粒亚单位疫苗两种疫苗联合应用后S抗原特异的细胞免疫应答(IFN-γELISpot分析)明显高于DNA疫苗或蛋白颗粒亚单位单独应用,其中皮内注射+电转结合蛋白颗粒亚单位疫苗联合免疫组可产生最强的细胞免疫应答。这些研究为新型HBV治疗性疫苗的优化设计与合理应用提供了依据。
To develop a new and effective HBV therapeutic vaccine, an HBV DNA vaccine containing the PreS1 and S fusion gene was constructed, namely pVRC-HBSS1 (PreS121-47 aa fused at the carboxyl terminus of S antigen 1-223 aa) and CHO expression was prepared The same structure protein particle subunit vaccine HBSS1. In the Balb / C mice using different ways of DNA immunization (ie, intramuscular injection, electrosurgical injection and electroporation) priming three times, protein particle subunit vaccine (different adjuvant) intramuscular immunization boosted once, and then we analyze and compare The vaccines caused by each group of immune response characteristics. The results of antibody test showed that the levels of PreS1 and S-specific antibodies produced by intradermal injection combined with electroporation were higher than that of intramuscular injection. Furthermore, we found that S antigen-specific cellular immune response (IFN-γELISpot analysis) was significantly higher than that of DNA vaccine or protein particle subunit when DNA vaccine and protein particle subunit vaccine were used in combination. The combination of intradermal injection + electrotransport Protein particle subunit vaccine combined with the immune group can produce the strongest cellular immune response. These studies provide the basis for the optimal design and rational application of novel HBV therapeutic vaccines.