Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207-IHU Méditerranée Infection), Marseille, France.
Emerg Microbes Infect. 2018 Sep 26;7(1):161. doi: 10.1038/s41426-018-0161-7.
Zika virus (ZIKV) has recently become dispersed throughout the tropics and sub-tropics, causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. In this study, we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared different constructs and confirmed the need to modify the cleavage site between the pre-peptide and prM protein. Genotypic characterization of the chimeras indicated that the emergence of compensatory mutations in the E protein was required to restore viral replicative fitness. Using an immunocompromised mouse model, we demonstrated that mice infected with the chimeric virus produced levels of neutralizing antibodies that were close to those observed following infection with ZIKV. Furthermore, pre-immunized mice were protected against viscerotropic and neuroinvasive disease following challenge with a heterologous ZIKV strain. These data provide a sound basis for the future development of this ZIKV vaccine candidate.
寨卡病毒（ZIKV）最近已在热带和亚热带地区传播，导致与先天性疾病和神经并发症相关的流行。目前尚无针对 ZIKV 的商业疫苗。在这项研究中，我们描述了一种嵌合病毒的初步开发，该病毒包含 ZIKV 流行株的 prM/E 蛋白，并入黄热 17-D 减毒骨架。使用多功能且快速的 ISA（感染性亚基因组扩增子）反向遗传学方法，我们比较了不同的构建体，并证实需要修饰前肽和 prM 蛋白之间的切割位点。嵌合病毒的基因型特征表明，需要 E 蛋白中的补偿性突变来恢复病毒复制适应性。使用免疫功能低下的小鼠模型，我们证明感染嵌合病毒的小鼠产生的中和抗体水平接近于感染 ZIKV 后观察到的水平。此外，预先免疫的小鼠在受到异源 ZIKV 株的挑战时，可免受内脏嗜性和神经侵袭性疾病的侵害。这些数据为该 ZIKV 疫苗候选物的未来发展提供了可靠的基础。
