Dengue results in substantial human morbidity and significant socio-economic impacts, but a specific dengue therapeutic is not available. The currently available dengue vaccine has low efficacy and high rate of adverse effects, necessitating different strategies for the development of a safer and more efficient vaccine against dengue virus. We describe here a hybrid combination of different-sized gold nanoparticles (AuNPs) and domain III of envelope glycoprotein derived from serotype 2 of dengue virus (EDIII) as dengue subunit vaccine. The efficacy of the EDIII-functionalized AuNPs (AuNP-E) to induce neutralizing antibody in BALB/c mice is evaluated. Obtained results show that AuNP-E induced a high level of antibody which mediates serotype-specific neutralization of dengue virus. More importantly, the level of antibody is dependent on both the size of AuNPs and the concentration of AuNP-E, implicating the possibility to modulate it through adjusting these parameters. These results represent an important step towards the development of tetravalent AuNP-based subunit dengue vaccine.

Statement of Significance

This research presents a novel subunit vaccine against dengue virus using a hybrid comprising gold nanoparticles (AuNPs) and domain III of envelop protein (EDIII). We proved the neutralizing activity of anti-EDIII antibody induced in immunized mice on Dengue virus serotype 2 in an AuNP core size and concentration dependent manner. The hybrid concept behind this work could also be adopted for the development of a tetravalent vaccine against four serotypes of Dengue virus.

中文翻译：

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金纳米颗粒亚单位疫苗对登革热病毒的大小依赖性中和活性。

登革热会导致严重的人类发病率和重大的社会经济影响，但尚无特定的登革热治疗剂。当前可获得的登革热疫苗具有低功效和高不良反应率，因此需要不同的策略来开发针对登革热病毒的更安全，更有效的疫苗。我们在这里描述了不同大小的金纳米粒子（AuNPs）和来自登革热病毒（EDIII）血清型2的包膜糖蛋白的结构域III的杂交组合，作为登革热亚单位疫苗。评估了EDIII功能化的AuNPs（AuNP-E）在BALB / c小鼠中诱导中和抗体的功效。获得的结果表明，AuNP-E诱导了高水平的抗体，该抗体介导了登革热病毒血清型特异性中和。更重要的是，抗体的水平取决于AuNPs的大小和AuNP-E的浓度，这意味着可以通过调节这些参数来调节抗体。这些结果代表了开发基于四价AuNP的亚单位登革热疫苗的重要一步。

重要声明

这项研究提出了一种新型的针对登革热病毒的亚单位疫苗，该疫苗使用了包含金纳米颗粒（AuNPs）和包裹蛋白III结构域（EDIII）的杂种。我们证明了以AuNP核心大小和浓度依赖性方式在免疫小鼠中对登革热病毒血清型2诱导的抗EDIII抗体的中和活性。这项工作背后的混合概念也可以用于开发针对四种血清型登革热病毒的四价疫苗。