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A DNA vaccine encoding the E protein of West Nile Virus is protective and can be boosted by recombinant domain DIII

机译:编码西尼罗河病毒E蛋白的DNA疫苗具有保护性,可通过重组结构域DIII加强

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West Nile Virus (WNV) is an emerging pathogenic flavivirus with increasing distribution worldwide. Birds are the natural host of the virus, but also mammals, including humans, can be infected. In some cases, a WNV infection can be associated with severe neurological symptoms. All currently available WNV vaccines are in the veterinary sector, and there is a need to develop safe and effective immunization technologies, which can also be used in humans. An alternative to current vaccination methods is DNA immunization. Most current DNA vaccine candidates against flaviviruses simultaneously express the viral envelope (E) and membrane (prM) proteins, which leads to the formation of virus-like particles. Here we generated a DNA plasmid, which expresses only the E-protein ectodomain. Vaccination of mice stimulated anti-WNV T-cell responses and neutralizing antibodies that were higher than those obtained after immunizing with a recombinant protein previously shown to be a protective WNV vaccine. A single dose of the plasmid was sufficient to protect animals from a lethal challenge with the virus. Moreover, immunogenicity could be boosted when DNA injection was followed by immunization with recombinant domain DIII of the E-protein. This resulted in significantly enhanced neutralizing antibody titers and a more prominent cellular immune response. The results suggest that the WNV E-protein is sufficient as a protective antigen in DNA vaccines and that protection can be significantly improved by adding a recombinant protein boost to the DNA prime
机译:西尼罗河病毒(WNV)是一种新兴的致病性黄病毒,在全球范围内分布日益广泛。鸟类是病毒的天然宿主,但包括人类在内的哺乳动物也可以被感染。在某些情况下,WNV感染可能与严重的神经系统症状有关。当前所有可用的WNV疫苗都在兽医领域,因此需要开发安全有效的免疫技术,也可以将其用于人类。当前疫苗接种方法的替代方法是DNA免疫。当前针对黄病毒的大多数DNA候选疫苗同时表达病毒包膜(E)和膜(prM)蛋白,这导致形成病毒样颗粒。在这里,我们生成了仅表达E蛋白胞外域的DNA质粒。小鼠的疫苗接种刺激了抗WNV T细胞反应和中和抗体,这些抗体的免疫力高于用先前证明是保护性WNV疫苗的重组蛋白免疫后获得的抗体。单剂量的质粒足以保护动物免受病毒的致命攻击。此外,当DNA注射后再用E蛋白的重组结构域DIII进行免疫时,免疫原性可以得到增强。这导致中和抗体滴度显着提高,并且细胞免疫反应更为显着。结果表明,WNV E蛋白足以作为DNA疫苗中的保护性抗原,并且可以通过向DNA引物中添加重组蛋白增强剂来显着改善保护性

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