Gong Jun-Yuan, Liu Xin, Dong Yan, Zhou Tian-Hong, Li Jun-Wu
Department of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, P.R. China.
Biomed Rep. 2013 Mar;1(2):251-256. doi: 10.3892/br.2012.47. Epub 2012 Dec 10.
A total of 10-20% of the population remains unresponsive or weakly responsive to hepatitis B vaccine, which is composed of hepatitis B surface antigen HBsAg (S protein). Therefore, it is necessary to develop a hepatitis B vaccine with a better penetrating and responsive rate. In the present study, a plasmid pVAX1-L-GM was constructed and its immunomodulatory effect of as hepatitis B virus (HBV) DNA vaccine was analyzed through the immunization of BALB/c mice. Immune responses were measured after immunization by anti-HBsAg, proliferation of splenocytes, the number of CD4 and CD8 molecules, CTL cytotoxicity, cytokines of IFN-γ and IL-2 secretion assays. Following the immunization, mice in the pVAX1-L-GM group produced antibody 2 weeks earlier compared to the control plasmid pVAX1 and pVAX1HBsAg groups and antibody levels showed significant differences. Enhanced HBsAg-specific splenocyte proliferation as well as specific cytotoxic activities of splenic CTLs were also detected. Furthermore, pVAX1-L-GM plasmid increased the number of CD4 and CD8 molecules on the surface of the spleen T cell and the level of IFN-γ, IL-2 secretion. pVAX1-L-GM induced a specific immune response in mice and enhanced the immune effect. Thus, a foundation was laid for developing immunogenicity of a better prevention and treatment of HBV via a hepatitis B vaccine.
总计10%-20%的人群对由乙肝表面抗原HBsAg(S蛋白)组成的乙肝疫苗无反应或反应较弱。因此,有必要研发一种具有更高渗透率和反应率的乙肝疫苗。在本研究中,构建了质粒pVAX1-L-GM,并通过对BALB/c小鼠进行免疫来分析其作为乙肝病毒(HBV)DNA疫苗的免疫调节作用。免疫后通过抗HBsAg、脾细胞增殖、CD4和CD8分子数量、CTL细胞毒性、IFN-γ和IL-2分泌细胞因子检测来测量免疫反应。免疫后,pVAX1-L-GM组小鼠产生抗体的时间比对照质粒pVAX1和pVAX1HBsAg组提前2周,且抗体水平存在显著差异。还检测到增强的HBsAg特异性脾细胞增殖以及脾CTL的特异性细胞毒性活性。此外,pVAX1-L-GM质粒增加了脾T细胞表面CD4和CD8分子的数量以及IFN-γ、IL-2的分泌水平。pVAX1-L-GM在小鼠中诱导了特异性免疫反应并增强了免疫效果。因此,为通过乙肝疫苗更好地预防和治疗HBV的免疫原性奠定了基础。