Richner Justin M, Jagger Brett W, Shan Chao, Fontes Camila R, Dowd Kimberly A, Cao Bin, Himansu Sunny, Caine Elizabeth A, Nunes Bruno T D, Medeiros Daniele B A, Muruato Antonio E, Foreman Bryant M, Luo Huanle, Wang Tian, Barrett Alan D, Weaver Scott C, Vasconcelos Pedro F C, Rossi Shannan L, Ciaramella Giuseppe, Mysorekar Indira U, Pierson Theodore C, Shi Pei-Yong, Diamond Michael S
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Cell. 2017 Jul 13;170(2):273-283.e12. doi: 10.1016/j.cell.2017.06.040.
The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.
寨卡病毒（ZIKV）的出现及其与先天性畸形的关联促使了疫苗的迅速研发。尽管多种病毒疫苗平台在动物实验中已证实有效，但尚无研究涉及孕期的保护效果。我们在小鼠中测试了两种疫苗平台，一种是脂质纳米颗粒包裹的编码ZIKV prM和E基因的修饰mRNA疫苗，另一种是编码无糖基化NS1蛋白的减毒活ZIKV毒株，以评估它们预防病毒传播给胎儿的能力。在胚胎第6天（E6）用异源ZIKV毒株攻击接种疫苗的母鼠，并在E13进行评估，结果显示母体、胎盘和胎儿组织中的病毒RNA水平显著降低，从而预防了胎盘损伤和胎儿死亡。由于修饰mRNA和减毒活疫苗平台可在小鼠中限制ZIKV的宫内传播，因此有必要在人类中进一步研发以预防先天性寨卡病毒综合征。
