Vaccination of mice using the West Nile virus E-protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects mice against a lethal challenge.
Vaccination of mice using the West Nile virus E-protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects mice against a lethal challenge.
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DOI：
10.1371/journal.pone.0087837
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sanders NN
中科院分区：
文献类型：
--
作者：
De Filette M;Soehle S;Ulbert S;Richner J;Diamond MS;Sinigaglia A;Barzon L;Roels S;Lisziewicz J;Lorincz O;Sanders NN
西尼罗河病毒(WNV)是一种蚊媒黄病毒，在非洲、中东、欧洲和美国流行。目前尚无抗病毒治疗或人类疫苗可用于治疗或预防西尼罗河病毒感染。DNA质粒型疫苗代表了一种控制传染病的新方法。在啮齿动物身上，DNA疫苗已被证明可以诱导B细胞和细胞毒性T细胞反应，并防止广泛的感染。在本研究中，我们用线性聚乙烯亚胺(LPEI)共价结合甘露糖，构建了表达西尼罗河病毒E蛋白胞外区的纳米粒DNA载体，并检测了该疫苗对小鼠致死性西尼罗河病毒感染的保护作用。用1PEI-甘露糖制成的西尼罗河病毒DNA疫苗，通过不同的给药途径(肌肉注射、皮内注射和局部注射)免疫小鼠两次(初始-增强方案)。同时，对纯化的重组西尼罗河病毒包膜(E)蛋白的异源增强作用进行了评估。虽然DNA免疫后没有产生明显的E蛋白特异性体液反应，但DNA免疫小鼠的蛋白增强导致总中和抗体效价显著增加。用ELISPOT法检测E特异性IL-4T细胞免疫应答，流式细胞仪检测CD8+特异性干扰素-γ的表达。使用异种免疫方案的攻击实验显示，对同源和强毒的西尼罗河病毒感染具有保护性免疫。
West Nile virus (WNV) is a mosquito-borne flavivirus that is endemic in Africa, the Middle East, Europe and the United States. There is currently no antiviral treatment or human vaccine available to treat or prevent WNV infection. DNA plasmid-based vaccines represent a new approach for controlling infectious diseases. In rodents, DNA vaccines have been shown to induce B cell and cytotoxic T cell responses and protect against a wide range of infections. In this study, we formulated a plasmid DNA vector expressing the ectodomain of the E-protein of WNV into nanoparticles by using linear polyethyleneimine (lPEI) covalently bound to mannose and examined the potential of this vaccine to protect against lethal WNV infection in mice. Mice were immunized twice (prime – boost regime) with the WNV DNA vaccine formulated with lPEI-mannose using different administration routes (intramuscular, intradermal and topical). In parallel a heterologous boost with purified recombinant WNV envelope (E) protein was evaluated. While no significant E-protein specific humoral response was generated after DNA immunization, protein boosting of DNA-primed mice resulted in a marked increase in total neutralizing antibody titer. In addition, E-specific IL-4 T-cell immune responses were detected by ELISPOT after protein boost and CD8+ specific IFN-γ expression was observed by flow cytometry. Challenge experiments using the heterologous immunization regime revealed protective immunity to homologous and virulent WNV infection.
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影响因子：
5.5
作者：
Jones, Suzanne;Evans, Kirsten;Loudon, Peter T.
通讯作者：
Loudon, Peter T.
影响因子：
14
作者：
Kim, Tae-il;Baek, Jung-un;Park, Jong-sang
通讯作者：
Park, Jong-sang
影响因子：
11.8
作者：
Gubler, Duane J.
通讯作者：
Gubler, Duane J.
影响因子：
4.8
作者：
Diebold, SS;Kursa, P;Zenke, M
通讯作者：
Zenke, M
DOI：
10.1023/a:1022975705406
发表时间：
2002-11-01
期刊：
Somatic Cell and Molecular Genetics
影响因子：
--
作者：
Diebold, Sandra S.;Plank, Christian;Zenke, Martin
通讯作者：
Zenke, Martin