The Second Division of Viral Vaccines; National Institute for the Control of Pharmaceutical and Biological Products, Beijing, PR China.
Virol J. 2011 Feb 23;8:78. doi: 10.1186/1743-422X-8-78.
Hepatitis B vaccine adjuvant, alum, is generally used for vaccination although it does not stimulate Th1 immunity and 10% of the population has low or no antibody response. Efforts have been continued to find more efficient vaccine adjuvants for better antibody response as well as stimulation of Th1 immunity.
CpG DNA was used as an adjuvant for recombinant HBsAg to immunize 6- to 8-week-old female BALB/c mice with or without alum for different dosages. The production of HBsAb, CD80 and CD86 from dendritic cells, and cytokines IL-10, IL12, etc., were analyzed and compared for the performance of immunization.
5-20 μg CpG DNA had the best co-stimulation effect of HBsAb serum conversion for mice vaccinated with recombinant expressed HBsAg. The mice vaccinated with recombinant 20 μg CpG DNA and regular vaccine (containing alum adjuvant) had the highest concentration of antibody production. IL-12b, IL-12a and IL10 mRNA reached to the peak level between 3 and 6 hours after the CpG DNA induction in splenocytes. The expression levels of CD80 and CD86 leucocyte surface molecules were increased with 20 μg CpG DNA alone or with 20 μg CpG DNA and 4 μg HBsAg.
Our results confirmed the adjuvant effect of CpG DNA for HBsAg in the mouse model. The increase of IL10 and IL12 production suggested the involvement of Th1 cell activation. The activation of CD80 and CD86 molecules by CpG-ODN might be part of the mechanism of T/B cells coordination and the enhancement of recombinant HBsAg induced immune response.
乙型肝炎疫苗佐剂明矾通常用于接种疫苗,尽管它不能刺激 Th1 免疫,并且有 10%的人群对抗体的反应较低或没有。人们一直在努力寻找更有效的疫苗佐剂,以获得更好的抗体反应,并刺激 Th1 免疫。
CpG DNA 被用作重组 HBsAg 的佐剂,用或不用明矾对 6-8 周龄雌性 BALB/c 小鼠进行免疫接种,剂量不同。分析比较树突状细胞产生的 HBsAb、CD80 和 CD86 以及细胞因子 IL-10、IL12 等,以评估免疫效果。
5-20μg CpG DNA 对重组 HBsAg 疫苗接种的小鼠具有最佳的协同刺激 HBsAb 血清转化率。用重组 20μg CpG DNA 和常规疫苗(含明矾佐剂)免疫的小鼠产生的抗体浓度最高。CpG DNA 诱导后 3-6 小时,脾细胞中 IL-12b、IL-12a 和 IL10 mRNA 达到峰值水平。单独使用 20μg CpG DNA 或与 20μg CpG DNA 和 4μg HBsAg 一起使用时,白细胞表面分子 CD80 和 CD86 的表达水平增加。
我们的结果证实了 CpG DNA 对乙型肝炎表面抗原(HBsAg)在小鼠模型中的佐剂作用。IL10 和 IL12 产量的增加表明 Th1 细胞的激活。CpG-ODN 激活 CD80 和 CD86 分子可能是 T/B 细胞协调和增强重组 HBsAg 诱导免疫反应的机制之一。