Chen Hong, Deng Yao, Tan Wenjie, Wang Wen, Yin Xiao, Guan Jie, Wang Wenling, Ruan Li
Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China.
Sheng Wu Gong Cheng Xue Bao. 2010 Jan;26(1):74-8.
We previous reported the development of novel hepatitis B virus(HBV) vaccine containing the surface antigen(S) plus PreS1 fusion derived from Chinese hamster ovary (CHO) cells system. In this study, we analyzed the impact of different adjuvants on immunogenicity of the HBV particle vaccine in Balb/C mice, including alum alone, CpG oligodeoxynucleotides (CpG-ODN) alone and CpG-ODN in combination with alum adjuvant. We first detected the antigen specific humoral response in mice, including total IgG antibody and IgG subtyping. Then, we characterized the specific cell-mediated immune (CMI) response by detection of gamma-interferon secreting splenocytes after stimulating with S or PreS1 peptide pool. Our results showed that: CpG-ODN adjuvanted vaccine could rapidly induce higher level of anti-PreS 1 and anti-S antibodies, and a higher ratio of IgG2a/IgG1 antibody than that of alum adjuvanted vaccine. At the same time, CpG-ODN adjuvanted vaccine induced robust antigen-specific cellular immune responses in mice, which was superior to that of alum adjuvanted vaccine and CpG-ODN in combination with alum adjuvanted vaccine; however, the vaccine candidate with CpG-ODN in combination with alum adjuvant induced highest anti-S antibody and mixed IgG subclasses in mice after twice immunization. There exists dominant HBV CMI epitopes in the N-terminal of S antigen. These results provided important evidence that CpG-ODN adjuvanted HBSS1 particles vaccine may serve as a novel candidate in the development of new preventive and therapeutic agents against hepatitis B infection.
我们之前报道了一种新型乙肝病毒(HBV)疫苗的研发,该疫苗包含来源于中国仓鼠卵巢(CHO)细胞系统的表面抗原(S)加前S1融合蛋白。在本研究中,我们分析了不同佐剂对Balb/C小鼠中HBV颗粒疫苗免疫原性的影响,包括单独的明矾、单独的CpG寡脱氧核苷酸(CpG-ODN)以及CpG-ODN与明矾佐剂联合使用。我们首先检测了小鼠体内的抗原特异性体液反应,包括总IgG抗体和IgG亚类分型。然后,我们通过检测用S或前S1肽库刺激后分泌γ干扰素的脾细胞来表征特异性细胞介导免疫(CMI)反应。我们的结果表明:CpG-ODN佐剂疫苗能快速诱导更高水平的抗前S1和抗S抗体,以及比明矾佐剂疫苗更高的IgG2a/IgG1抗体比例。同时,CpG-ODN佐剂疫苗在小鼠中诱导了强大的抗原特异性细胞免疫反应,优于明矾佐剂疫苗和CpG-ODN与明矾佐剂联合使用的疫苗;然而,CpG-ODN与明矾佐剂联合使用的候选疫苗在两次免疫后在小鼠中诱导出最高水平的抗S抗体和混合IgG亚类。在S抗原的N端存在主要的HBV CMI表位。这些结果提供了重要证据,表明CpG-ODN佐剂的HBSS1颗粒疫苗可能成为开发预防和治疗乙肝感染新制剂的新型候选疫苗。