Novel vaccination approach for dengue infection based on recombinant immune complex universal platform
Novel vaccination approach for dengue infection based on recombinant immune complex universal platform
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DOI：
10.1016/j.vaccine.2015.02.036
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发表时间：
2015-04-08
期刊：
影响因子：
5.5
通讯作者：
Mason, Hugh S.
中科院分区：
文献类型：
--
作者：
Kim, Mi-Young;Reljic, Rajko;Mason, Hugh S.
登革热感染在热带许多流行地区呈上升趋势。疫苗接种仍然是预防这种潜在致命病毒性疾病的最现实的策略，但目前还没有有效的疫苗可以保护所有四种已知的登革热病毒血清型。本研究描述了一种基于重组免疫复合物（RIC）的新型登革热疫苗接种方法的产生和测试。我们在现有的埃博拉RIC上模拟登革热RIC（Phoolcharoen等人，Proc Natl Acad Sci USA 2011;108（Dec（51））：20695），但进行了关键修改，允许形成通用RIC平台，其可以容易地适用于其他病原体。这是通过仅保留6D 8抗埃博拉mAb的结合表位来实现的，然后将其与登革热共有E3结构域（cEDIII）融合，产生杂合的登革热-埃博拉RIC（DERIC）。我们使用基于双生病毒的表达系统在烟草植物中表达了这些分子的人类和小鼠版本。通过蛋白G亲和层析从植物提取物中纯化后，DERIC与补体的C1 q组分结合，从而确认功能性。重要的是，在小鼠免疫后，在没有外源性佐剂的情况下，DERIC诱导了有效的病毒中和抗cEDIII体液免疫应答。我们的结论是，这些自我辅助免疫原有可能被开发为一种新的候选疫苗登革热感染，并提供了一个通用的RIC平台与其他抗原一起使用的基础。(C)2015爱思唯尔有限公司版权所有。
Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens. (C) 2015 Elsevier Ltd. All rights reserved.