Chen Hong, Deng Yao, Tan Wenjie, Wang Wen, Guan Jie, Wen Bo, Yin Xiao, Ruan Li
Biotech Center for Viral Diseases Emergency, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China.
Sheng Wu Gong Cheng Xue Bao. 2011 Jan;27(1):95-100.
To develop novel and effective HBV therapeutic vaccine, we constructed an expression vector, pVRC-HBSS1, in which PreS1 (21-47aa) coding gene fused to the C-terminal of the S (1-223 aa) coding gene of HBV, and prepared the protein particle vaccine HBSS1 that consist of S and PreS1 fusion antigen derived from CHO system. We immunized mice by priming three times with DNA vaccine via different methods (i.e., intramuscular injection, intradermal injection with electroporation), then boosting once with protein particle vaccine. We analyzed the immune response among various vaccination groups. The higher level of S or PreS1 specific antibodies was detected in the group via intradermal injection with electroporation, compared with that of direct intramuscular injection. We further found that the specific cellular immune responses (IFN-gamma ELISpot analysis) in the group priming with DNA vaccines and boosting with protein subunit vaccine particles, was significantly higher than that of the DNA or protein particle subunit alone. Moreover, combination vaccination priming with intradermal injection DNA via electroporation and boosting with protein particle induced the strongest cellular immune response. These results provide a basis for rational design and application of the novel HBV therapeutic vaccine.
为研发新型有效的乙肝病毒（HBV）治疗性疫苗，我们构建了一种表达载体pVRC - HBSS1，其中PreS1（21 - 47氨基酸）编码基因与HBV的S（1 - 223氨基酸）编码基因的C末端融合，并制备了由源自CHO系统的S和PreS1融合抗原组成的蛋白颗粒疫苗HBSS1。我们通过不同方法（即肌肉注射、电穿孔皮内注射）用DNA疫苗对小鼠进行三次初免，然后用蛋白颗粒疫苗进行一次加强免疫。我们分析了各个疫苗接种组的免疫反应。与直接肌肉注射组相比，电穿孔皮内注射组检测到更高水平的S或PreS1特异性抗体。我们进一步发现，先用DNA疫苗初免并用蛋白亚单位疫苗颗粒加强免疫的组中的特异性细胞免疫反应（IFN -γ ELISpot分析）明显高于单独使用DNA或蛋白颗粒亚单位的组。此外，通过电穿孔皮内注射DNA初免并用蛋白颗粒加强免疫诱导了最强的细胞免疫反应。这些结果为新型HBV治疗性疫苗的合理设计和应用提供了依据。
