Plasmid DNA containing multiple CpG motifs triggers a strong immune response to hepatitis B surface antigen when combined with incomplete Freund's adjuvant but not aluminum hydroxide
Plasmid DNA containing multiple CpG motifs triggers a strong immune response to hepatitis B surface antigen when combined with incomplete Freund's adjuvant but not aluminum hydroxide
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当与不完全弗氏佐剂而非氢氧化铝结合时，含有多个 CpG 基序的质粒 DNA 会引发针对乙型肝炎表面抗原的强烈免疫反应。
DOI：
10.3892/mmr.2012.1079
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发表时间：
2012-12-01
影响因子：
3.4
通讯作者：
Yang, Li
中科院分区：
文献类型：
--
作者：
Luo, Zichao;Shi, Huashan;Yang, Li
佐剂是重组蛋白疫苗的重要组成部分，其通常免疫原性差。几十年来，寻找新的疫苗佐剂主要是经验性的。此外，已经系统地研究了一种以上佐剂加抗原的组合。含有非甲基化CpG基序的寡聚脱氧核苷酸（CpG ODN）的质粒DNA作为DNA疫苗的佐剂，已显示出强大的免疫刺激作用。在我们的研究中，含有16个额外的CpG ODN（pv-16 CpG）的质粒DNA与氢氧化铝（AL）或不完全弗氏佐剂（IFA）的组合被用作B表面抗原（HBsAg）疫苗的佐剂，以免疫C57 BL/6 J小鼠。采用ELISA和ELISPOT法分析疫苗的免疫效果。CpG质粒与IFA联用可显著提高抗-HBs滴度和血清阳转率，而与AL联用则无显著性差异。此外，ELISPOT测定表明，悬浮在IFA中的pv-16 CpG诱发了强的辅助性T细胞1（Th 1）免疫应答和高IFN-γ产生。这些结果表明，悬浮在IFA中的pv-16 CpG能够诱导对HBsAg的细胞和体液免疫应答，并证实其作为佐剂用于蛋白疫苗的潜力。
Adjuvants are important components of recombinant protein vaccines which are often poorly immunogenic. For decades, the search for new vaccine adjuvants has been predominantly empirical. In addition, combinations of more than one adjuvant plus antigen have been systematically studied. Plasm id DNA containing additional oligodeoxynucletides with unmethylated CpG motifs (CpG ODN) entrapped in liposomes has been used as an adjuvant for DNA vaccines and has shown powerful immunostimulatory functions. In our study, the combination of plasmid DNA containing 16 additional CpG ODNs (pv-16CpG) and aluminum hydroxide (AL) or incomplete Freund's adjuvant (I FA) was used as an adjuvant for a hepatitis B surface antigen (HBsAg) vaccine to immunize C57BL/6J mice. ELISA and ELISPOT assays were used to analyze the immunological effects of the novel vaccine. A significant enhancement of the anti-HBs titer and seroconversion was observed when the CpG plasmid was combined with I FA, but not with AL. In addition, anti-HBs antibody isotype analysis revealed that the combination of CpG plasmid and IFA induced a strong HBsAg-specific IgG2a response. Moreover, the ELISPOT assays suggested that pv-16CpG suspended in IFA evoked a strong T helper 1 (Th1) immune response and high IFN-gamma production. These results demonstrate that pv-16CpG suspended in IFA is able to induce cellular and humoral immune responses to HBsAg, and confirm its potential as an adjuvant for use in protein vaccines.