There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the β-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE.

目前还没有获得许可的针对寨卡病毒 (ZIKV) 的疗法或疫苗可以抵消其引起先天性疾病的可能性。针对 ZIKV 包膜蛋白的基于抗体的对策因担心交叉反应反应而受到阻碍，交叉反应反应会诱导异源黄病毒感染的抗体依赖性增强 (ADE)。非结构蛋白 1 (NS1) 是一种膜相关的分泌糖蛋白，在黄病毒复制和免疫逃避中发挥作用，但病毒颗粒中不存在。尽管一些研究表明针对 ZIKV NS1 的抗体具有保护作用，但其在先天性感染期间的活性尚不清楚。在这里，我们开发了小鼠和人类抗 NS1 单克隆抗体，可以保护非怀孕和怀孕小鼠免受 ZIKV 感染。抗体与细胞表面 NS1 结合的亲和力以及 Fc 效应子功能的参与与体内保护相关。保护性单克隆抗体映射到 β 平台翼域和环面中的暴露表位。抗 NS1 抗体提供了一种预防先天性 ZIKV 感染而不引起 ADE 的替代策略。