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通过将结核分枝杆菌Ag85B编码基因与BVP22编码基因连接构建的DNA疫苗的增强免疫应答和保护效力。

Enhanced immune response and protection efficacy of a DNA vaccine constructed by linkage of the Mycobacterium tuberculosis Ag85B-encoding gene with the BVP22-encoding gene.

作者信息

Yao Wanhong, Liu Shengwu, Qu Xueju, Xiao Shaobo, Liu Yan, Liu Junyan

机构信息

Department of Microbiology and Parasitology, School of Medicine, Wuhan University, Wuhan, PR China.

Department of Immunology, School of Medicine, Wuhan University, Wuhan, PR China.

出版信息

J Med Microbiol. 2009 Apr;58(Pt 4):462-468. doi: 10.1099/jmm.0.004267-0.

Abstract

Plasmid DNA vaccines have been widely explored for use in tuberculosis immunization but their immunogenicity needs improvement. In the present study, we incorporated the bovine herpesvirus 1 VP22 (BVP22)-encoding gene, which encodes a protein that demonstrates a capability for disseminating the expressed antigen to neighbouring cells, into a DNA vector in which it was fused to the Ag85B-encoding gene of Mycobacterium tuberculosis (Mtb), and investigated whether this linkage could enhance immune response and protective efficacy in C57BL/6 mice compared to plasmid DNA encoding Ag85B alone. After immunization in mice, Ag85B-specific ELISA antibodies and spleen lymphocyte proliferative responses induced by DNA co-expressing BVP22 and Ag85B were significantly higher than those obtained in mice immunized with Ag85B-encoding DNA alone, except for the number of gamma interferon secreting cells. In addition, based on histopathological examination and bacterial-load determination in lung and spleen, protection against intravenous Mtb H37Rv challenge evoked by the BVP22-Ag85B DNA immunization exceeded the response elicited by Ag85B DNA alone, which was not significantly different from that provided by Bacillus Calmette-Guérin (BCG). These results suggested that DNA vaccine consisting of BVP22 and Ag85B-encoding DNA enhanced immune response and protection against intravenous Mtb H37Rv challenge in mice, indicating that BVP22-encoding DNA might be a promising tool to enhance TB DNA vaccine efficacy.

摘要

质粒DNA疫苗已被广泛研究用于结核病免疫,但它们的免疫原性需要改进。在本研究中,我们将编码牛疱疹病毒1 VP22(BVP22)的基因(该基因编码一种能够将表达的抗原传播到邻近细胞的蛋白质)整合到一个DNA载体中,并将其与结核分枝杆菌(Mtb)的Ag85B编码基因融合,然后研究与单独编码Ag85B的质粒DNA相比,这种连接是否能增强C57BL/6小鼠的免疫反应和保护效力。在小鼠免疫后,除γ干扰素分泌细胞数量外,共表达BVP22和Ag85B的DNA诱导的Ag85B特异性ELISA抗体和脾淋巴细胞增殖反应显著高于单独用编码Ag85B的DNA免疫的小鼠。此外,基于组织病理学检查以及肺和脾中细菌载量的测定,BVP22-Ag85B DNA免疫引发的针对静脉注射Mtb H37Rv攻击的保护作用超过了单独Ag85B DNA引发的反应,且与卡介苗(BCG)提供的保护作用无显著差异。这些结果表明,由BVP22和编码Ag85B的DNA组成的DNA疫苗增强了小鼠的免疫反应以及对静脉注射Mtb H37Rv攻击的保护作用,表明编码BVP22的DNA可能是增强结核DNA疫苗效力的一种有前景的工具。

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