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基于保守基质表位的 DNA 疫苗可保护小鼠免受甲型流感病毒攻击。

A conserved matrix epitope based DNA vaccine protects mice against influenza A virus challenge.

机构信息

Department of Respiratory Virology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India.

出版信息

Antiviral Res. 2012 Jan;93(1):78-85. doi: 10.1016/j.antiviral.2011.10.021. Epub 2011 Nov 9.

Abstract

DNA vaccination represents a unique strategy to overcome the limitations of immunization with conventional vaccines which is restricted by the high variability of influenza viruses. We evaluated the protective efficacy of a plasmid DNA (pDNA), encoding an evolutionarily conserved epitope of viral matrix protein, against the influenza A virus infection. It was found that the mice immunized via the intra-muscular route purely elicited cell mediated immune response to the pDNA, with enhanced level of Th1 cytokines viz. IL-12 and IFNγ production in the stimulated splenocyte supernatant. The cytotoxic T lymphocytes in the spleen of immunized mice significantly lysed the virus-infected MDCK cells. A significant decrease in virus replication was also observed in the lungs of immunized mice and 83% of the mice were protected against the lethal challenge of influenza A viruses. These findings suggest that the plasmid DNA expressing a single matrix epitope may serve as a promising vaccine candidate to provide effective immunity in the susceptible (mouse) population.

摘要

DNA 疫苗接种代表了一种独特的策略,可以克服使用传统疫苗进行免疫的局限性,传统疫苗受到流感病毒高度变异性的限制。我们评估了编码病毒基质蛋白进化上保守表位的质粒 DNA(pDNA)对甲型流感病毒感染的保护效力。结果发现,通过肌肉内途径免疫的小鼠仅对 pDNA 产生细胞介导的免疫反应,刺激的脾细胞上清液中 Th1 细胞因子(如 IL-12 和 IFNγ)的水平增强。免疫小鼠脾脏中的细胞毒性 T 淋巴细胞可显著裂解感染病毒的 MDCK 细胞。在免疫小鼠的肺部也观察到病毒复制显著减少,83%的小鼠免受甲型流感病毒的致死性攻击。这些发现表明,表达单个基质表位的质粒 DNA 可能成为一种有前途的疫苗候选物,为易感(小鼠)人群提供有效的免疫。

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