Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA, 02142, USA.
The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
Sci Rep. 2017 Mar 21;7(1):252. doi: 10.1038/s41598-017-00193-w.
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-2D-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.
Zika 病毒(ZIKV)在美洲和南太平洋的爆发给人类健康带来了重大负担,因为 ZIKV 在胎儿发育过程中具有神经嗜性。针对 ZIKV 的疫苗候选物正在问世,但用于研究临床前模型中抗 ZIKV 反应的免疫工具,特别是 T 细胞反应,仍然很少。我们利用 RNA 纳米颗粒技术创建了一种疫苗候选物,该候选物在 C57BL/6 小鼠中通过 ELISA 检测到 ZIKV E 蛋白特异性 IgG 反应。使用该工具,我们鉴定了一种独特的 H-2D 限制性表位,用我们基于修饰树突状细胞的 RNA 纳米颗粒疫苗免疫的小鼠中存在 CD8 T 细胞反应。这些结果表明,该方法可用于评估新的候选抗原并确定免疫相关性,而无需使用活病毒。