Evaluation of a DNA vaccine candidate expressing prM-E-NS1 antigens of dengue virus serotype 1 with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) in immunogenicity and protection.
Evaluation of a DNA vaccine candidate expressing prM-E-NS1 antigens of dengue virus serotype 1 with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) in immunogenicity and protection.
复制标题
DOI：
10.1016/j.vaccine.2010.11.014
复制
发表时间：
2011-01
期刊：
影响因子：
5.5
通讯作者：
Qun Zheng;Dong-ying Fan;Na Gao;Hui Chen;Juan Wang;Ying Ming;Jieqiong Li;J. An
中科院分区：
文献类型：
--
作者：
Qun Zheng;Dong-ying Fan;Na Gao;Hui Chen;Juan Wang;Ying Ming;Jieqiong Li;J. An
登革热是最重要的蚊媒病毒性疾病之一。在过去的几年里，尽管在疫苗的开发上投入了大量的努力，但目前还没有获得许可的登革热疫苗。在本研究中，我们构建了携带登革病毒1型(DV1)PrM-E-NS1基因的DNA疫苗，其中含有或不带有粒细胞-巨噬细胞集落刺激因子(GM-CSF)基因，这是一种有吸引力的DNA疫苗佐剂。用表达病毒PRM-E-NS1的pCAG-DV1/E/NS1和共表达病毒PRM-E-NS1和GM-CsF的双顺反子表达载体pCAG-DV1-GM免疫小鼠，可产生长期的免疫球蛋白应答，脾细胞分泌高水平的干扰素-γ和白介素2，细胞毒T淋巴细胞活性强，并有足够的保护作用。这表明，免疫可诱导体液和细胞免疫反应，并在抵抗DV1攻击中发挥重要作用。有趣的是，pCAG-DV1/E/NS1或pCAG-DV1-GM诱导的免疫应答的大小、质量和保护能力似乎比pCAG-DV1/E(单独表达病毒PRM-E)更强。综上所述，我们证明PRM/E+NS1是一种适合于DV DNA疫苗研制的解决方案。
Dengue is one of the most important mosquito-borne viral diseases. In past years, although considerable effort has been put into the development of a vaccine, there is currently no licensed dengue vaccine. In this study, we constructed DNA vaccines that carried the prM-E-NS1 genes of dengue virus serotype 1 (DV1) with or without the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, an attractive DNA vaccine adjuvant. Immunization with the plasmid pCAG-DV1/E/NS1, which expresses viral prM-E-NS1, or the bicistronic plasmid pCAG-DV1-GM, which co-expresses viral prM-E-NS1 and GM-CSF, resulted in long-term IgG response, high levels of splenocyte-secreted interferon-γ and interleukin-2, strong cytotoxic T lymphocyte activity and sufficient protection in the DV1-challenged mice. This suggested that both humoral and cellular immune responses were induced by the immunizations and that they played important roles in protection against the DV1 challenge. Interestingly, the magnitude, quality and protective capacity of the immune responses induced by immunization with pCAG-DV1/E/NS1 or pCAG-DV1-GM seemed stronger than those induced by pCAG-DV1/E (expressing viral prM-E alone). Taken together, we demonstrated that prM/E plus NS1 would be a suitable solution for the development of a DNA vaccine against DV.