A highly optimized DNA vaccine confers complete protective immunity against high-dose lethal lymphocytic choriomeningitis virus challenge.
A highly optimized DNA vaccine confers complete protective immunity against high-dose lethal lymphocytic choriomeningitis virus challenge.
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DOI：
10.1016/j.vaccine.2010.12.064
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发表时间：
2011-09-09
期刊：
影响因子：
5.5
通讯作者：
Weiner, David B.
中科院分区：
文献类型：
--
作者：
Shedlock, Devon J.;Talbott, Kendra T.;Cress, Christina;Ferraro, Bernadette;Tuyishme, Steven;Mallilankaraman, Karthik;Cisper, Neil J.;Morrow, Matthew P.;Wu, Stephan J.;Kawalekar, Omkar U.;Khan, Amir S.;Sardesai, Niranjan Y.;Muthumani, Karuppiah;Shen, Hao;Weiner, David B.
防止感染是免疫的标志，也是有效疫苗接种的基础。由于多种原因，迫切需要开发新的、更安全和更有效的疫苗平台。在这方面，虽然“第一代”DNA疫苗的免疫原性较差，但新的基因“优化”策略和体内电穿孔（EP）的应用极大地提高了它们的效力。我们开发了一种高度优化的质粒 DNA 疫苗，可表达淋巴细胞脉络丛脑膜炎病毒 (LCMV) 核衣壳蛋白 (NP)，并使用 LCMV 攻击模型（研究感染和免疫的金标准）对其进行评估。当肌肉注射 EP 时，会引发强烈的 NP 特异性细胞和体液免疫反应，其程度接近急性 LCMV 感染后的反应程度。此外，这些反应能够针对高剂量、通常致命的病毒攻击提供 100% 的保护。这是第一种在接种疫苗后八周内赋予完全保护性免疫力的非传染性疫苗，并展示了“下一代”DNA 疫苗的潜在效用。
Protection against infection is the hallmark of immunity and the basis of effective vaccination. For a variety of reasons there is a great demand to develop new, safer and more effective vaccine platforms. In this regard, while ‘first-generation’ DNA vaccines were poorly immunogenic, new genetic ‘optimization’ strategies and the application of in vivo electroporation (EP) have dramatically boosted their potency. We developed a highly optimized plasmid DNA vaccine that expresses the lymphocytic choriomeningitis virus (LCMV) nucleocapsid protein (NP) and evaluated it using the LCMV challenge model, a gold standard for studying infection and immunity. When administered intramuscularly with EP, robust NP-specific cellular and humoral immune responses were elicited, the magnitudes of which approached those following acute LCMV infection. Furthermore, these responses were capable of providing 100% protection against a high-dose, normally lethal virus challenge. This is the first non-infectious vaccine conferring complete protective immunity up to eight weeks after vaccination and demonstrates the potential utility of ‘next-generation’ DNA vaccines.
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