HSP70 gene fused with Hantavirus S segment DNA significantly enhances the DNA vaccine potency against hantaviral nucleocapsid protein in vivo
HSP70 gene fused with Hantavirus S segment DNA significantly enhances the DNA vaccine potency against hantaviral nucleocapsid protein in vivo
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DOI：
10.1016/j.vaccine.2006.07.040
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发表时间：
2007-01-04
期刊：
影响因子：
5.5
通讯作者：
Yang, Shou Jing
中科院分区：
文献类型：
--
作者：
Li, Jing;Ye, Zheng Xu;Yang, Shou Jing
热休克蛋白(HSPs)可作为佐剂与多肽抗原或作为融合蛋白给予，从而提高疫苗接种效率。为评价热休克蛋白70(HSP70)对汉滩病毒核衣壳蛋白(NP)免疫原性的增强作用，将HSP70基因与汉滩病毒S段全长DNA(HTNV S DNA)基因连接，构建了新型嵌合型HTNV S-HSP70DNA疫苗载体。用该表达载体免疫C57BL/6小鼠，然后用同源重组蛋白加强免疫。采用ELISA法、流式细胞仪(FACS)、细胞毒试验和干扰素-γELISPOT法检测HTNV NP特异性抗体和细胞免疫应答。结果发现，与单纯接种S DNA或物理混合接种S DNA相比，接种S-HSP70DNA疫苗能显著提高小鼠血清中抗HTNVNP抗体水平、IgG2a/IgG1值、产生干扰素-γ的CD8(+)T细胞前体细胞百分率和细胞毒性T淋巴细胞(CTL)应答。相比之下，HSP70DNA或载体DNA免疫不能诱导显著水平的特异性抗体和CTL反应。因此，我们首次证明了基于HSP70的HTNV S DNA能够诱导针对HTNV NP的体液和细胞免疫应答，是一种有前途的HTNV感染DNA疫苗。(C)2006爱思唯尔有限公司。保留所有权利。
Heat shock proteins (HSPs) have been shown to act as adjuvants when coadministered with peptide antigens or given as fusion proteins and enhance the vaccination efficiency. To evaluate the enhancement of the potency of Hantaan virus (HTNV) nucleocapsid protein (NP) immunogenicity by heat shock protein 70 (HSP70), we developed a novel chimeric HTNV S-HSP70 DNA vaccine plasmid by genetically linking HSP70 gene to the full-length HTNV S segment DNA (HTNV S DNA). C57BL/6 mice were immunized with this plasmid followed by a subsequent boost with homologous recombinant protein. The levels of HTNV NP-specific antibody and cellular immune response were measured by use of ELISA, fluorescence activated cell sorter (FACS) analysis, cytotoxicity assay, and IFN-gamma ELISPOT assay. We found that HTNV S-HSP70 DNA vaccination significantly increased the levels of HTNV NP-specific antibody, IgG2a/IgG1 ratio, IFN-gamma producing CD8(+) T-cell precursor frequencies, and cytotoxic T lymphocyte (CTL) response when compared with immunization with HTNV S DNA alone or HTNV S DNA physically mixed with HSP70 DNA. By contrast, HSP70 DNA or vector DNA immunization could not induce appreciable levels of specific antibodies and CTL response. Thus, we demonstrate for the first time that HSP70-based HTNV S DNA can induce both humoral and cellular immune response specific for HTNV NP and is a promising candidate DNA vaccine for HTNV infection. (c) 2006 Elsevier Ltd. All rights reserved.