Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.

中文翻译：

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受孕前接种 DNA 疫苗可以保护暴露于寨卡病毒的怀孕猕猴免受长期病毒血症的影响，并改善胎儿的结局。


孕妇感染寨卡病毒 (ZIKV) 与先天性寨卡综合征 (CZS) 有关，尽管有几种疫苗正在临床试验中进行测试，但目前尚无疫苗可用。我们在先天性 ZIKV 感染的恒河猴模型中测试了 ZIKV DNA 疫苗 VRC5283 的功效。大多数动物疫苗实验都会在疫苗接种后几周或几个月内进行一定的病原体暴露。在现实世界中，人们在接种疫苗后数年或数十年会遇到病原体，或者如果病毒流行，则可能会反复接触病原体。为了更准确地模拟这种疫苗的使用方式，我们在受孕前对猕猴进行了免疫，然后在妊娠早期和中期将它们反复暴露于 ZIKV。与未免疫的动物相比，接种疫苗的动物母体病毒血症、早期胎儿流产、胎儿感染以及胎盘和胎儿脑部病理的峰值程度和持续时间显着降低。首次接触 ZIKV 当天疫苗诱导的中和抗体滴度与母体病毒血症的严重程度呈负相关，并且不存在长期病毒血症与更好的胎儿结局相关。这些数据支持 ZIKV 疫苗策略的进一步临床开发，以防止胎儿出现阴性结果。