The Zika virus (ZIKV) epidemic has resulted in congenital abnormalities in fetuses and neonates. Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV infection in mice, those recognizing the DENV E-dimer epitope (EDE) can neutralize ZIKV infection in cell culture. We evaluated the therapeutic activity of human monoclonal antibodies to DENV EDE for their ability to control ZIKV infection in the brains, testes, placentas, and fetuses of mice. A single dose of the EDE1-B10 antibody given 3 d after ZIKV infection protected against lethality, reduced ZIKV levels in brains and testes, and preserved sperm counts. In pregnant mice, wild-type or engineered LALA variants of EDE1-B10, which cannot engage Fcg receptors, diminished ZIKV burden in maternal and fetal tissues, and protected against fetal demise. Because neutralizing antibodies to EDE have therapeutic potential against ZIKV, in addition to their established inhibitory effects against DENV, it may be possible to develop therapies that control disease caused by both viruses.

中文翻译：

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登革热病毒 E-二聚体表位的人类抗体具有针对寨卡病毒感染的治疗活性。


寨卡病毒（ZIKV）流行已导致胎儿和新生儿先天性畸形。虽然一些交叉反应登革热病毒 (DENV) 特异性抗体可以增强小鼠中的 ZIKV 感染，但识别 DENV E-二聚体表位 (EDE) 的抗体可以中和细胞培养物中的 ZIKV 感染。我们评估了针对 DENV EDE 的人单克隆抗体控制小鼠大脑、睾丸、胎盘和胎儿中 ZIKV 感染的能力。 ZIKV 感染后 3 天给予单剂 EDE1-B10 抗体，可防止死亡，降低大脑和睾丸中的 ZIKV 水平，并保留精子数量。在怀孕小鼠中，EDE1-B10 的野生型或工程化 LALA 变体不能与 Fcg 受体结合，可以减少母体和胎儿组织中的 ZIKV 负担，并防止胎儿死亡。由于 EDE 中和抗体具有针对 ZIKV 的治疗潜力，除了对 DENV 具有既定的抑制作用外，因此有可能开发出控制这两种病毒引起的疾病的疗法。