Chen Hong, Wen Bo, Deng Yao, Wang Wen, Yin Xiao, Guan Jie, Ruan Li, Tan Wenjie
State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 100 Yingxin Street, Xuanwu District, Beijing 100052, People's Republic of China.
Clin Vaccine Immunol. 2011 Nov;18(11):1789-95. doi: 10.1128/CVI.05113-11. Epub 2011 Sep 7.
To develop a novel, effective HBV therapeutic vaccine, we constructed two HBV DNA immunogens that contained PreS1, HBSS1, and HBCS1. Several delivery methods, such as intramuscular (i.m.) injection, intramuscular injection plus electroporation (i.m.-EP), and intradermal injection plus electroporation (i.d.-EP) were used in a murine model to analyze and compare the immune responses that were induced by the DNA immunogens. We found that i.d.-EP accelerated specific antibody seroconversion and produced high antibody (anti-PreS1, anti-S, and anti-C antibody) titers after HBSS1 and HBCS1 immunization. Combining the HBSS1 and HBCS1 DNA immunogens with i.d.-EP produced the strongest multiantigen (PreS1, S, and C)-specific cellular immune response and the highest specific PreS1 antibody levels. The results indicated that DNA immunization using HBSS1 and HBCS1 might be an ideal candidate, with its ability to elicit robust B and T cell immune responses against multiantigen when combined with optimized delivery technology. The present study provides a basis for the design and rational application of a novel HBV DNA vaccine.
为开发一种新型、有效的乙肝病毒治疗性疫苗，我们构建了两种包含前S1、乙肝表面抗原小蛋白1（HBSS1）和乙肝核心抗原小蛋白1（HBCS1）的乙肝病毒DNA免疫原。在小鼠模型中使用了几种递送方法，如肌肉注射、肌肉注射加电穿孔（i.m.-EP）和皮内注射加电穿孔（i.d.-EP），以分析和比较DNA免疫原诱导的免疫反应。我们发现，皮内注射加电穿孔加速了特异性抗体血清转化，并在HBSS1和HBCS1免疫后产生了高抗体（抗前S1、抗S和抗C抗体）滴度。将HBSS1和HBCS1 DNA免疫原与皮内注射加电穿孔相结合，产生了最强的多抗原（前S1、S和C）特异性细胞免疫反应和最高的特异性前S1抗体水平。结果表明，使用HBSS1和HBCS1进行DNA免疫可能是一个理想的候选方案，当与优化的递送技术相结合时，它能够引发针对多抗原的强大B细胞和T细胞免疫反应。本研究为新型乙肝病毒DNA疫苗的设计和合理应用提供了依据。
