An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model.

An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model.
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DOI:
10.1038/s41598-017-00193-w
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发表时间:
2017-03-21
期刊:
影响因子:
4.6
通讯作者:
Ploegh HL
Ploegh HL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chahal JS;Fang T;Woodham AW;Khan OF;Ling J;Anderson DG;Ploegh HL

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寨卡病毒(ZIKV)在美洲和南太平洋的暴发给人类健康带来了巨大的负担,因为ZIKV在胎儿发育过程中具有神经营养作用。针对ZIKV的候选疫苗正在上线,但在临床前模型中研究抗ZIKV反应的免疫学工具仍然很少,特别是T细胞反应。我们利用RNA纳米颗粒技术创建了一种候选疫苗,通过ELISA法检测该疫苗在C57BL/6小鼠中诱导了ZIKV E蛋白特异性的免疫球蛋白G反应。使用这个工具,我们确定了一个独特的H-2DB限制性表位,在我们改进的基于树枝状大分子的RNA纳米颗粒疫苗免疫的小鼠中,对该表位有CD8+T细胞反应。这些结果表明,这种方法可以用于评估新的候选抗原和识别免疫关联,而不需要使用活病毒。
The Zika virus (ZIKV) outbreak in the Americas and South Pacific poses a significant burden on human health because of ZIKV’s neurotropic effects in the course of fetal development. Vaccine candidates against ZIKV are coming online, but immunological tools to study anti-ZIKV responses in preclinical models, particularly T cell responses, remain sparse. We deployed RNA nanoparticle technology to create a vaccine candidate that elicited ZIKV E protein-specific IgG responses in C57BL/6 mice as assayed by ELISA. Using this tool, we identified a unique H-2Db-restricted epitope to which there was a CD8+ T cell response in mice immunized with our modified dendrimer-based RNA nanoparticle vaccine. These results demonstrate that this approach can be used to evaluate new candidate antigens and identify immune correlates without the use of live virus.