Department of Pathology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.
Department of Immunology and Microbiology and International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sci Transl Med. 2017 Oct 4;9(410). doi: 10.1126/scitranslmed.aan8184.
Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasmablasts of a ZIKV-infected patient-SMZAb1, SMZAb2, and SMZAb5-directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fcγ receptor binding, thus eliminating potential therapy-mediated antibody-dependent enhancement. We administered a cocktail of these three nmAbs to nonhuman primates 1 day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum after challenge. Given that numerous antibodies have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses.
急需开发预防母体 Zika 病毒（ZIKV）感染及其随后胎儿发育并发症的疗法。我们从一名 Zika 病毒感染患者的浆母细胞中分离出三种强效的 Zika 病毒中和单克隆抗体（nmAbs）-SMZAb1、SMZAb2 和 SMZAb5-针对病毒的两个不同结构域。我们对这些 nmAbs 进行了 Fc LALA 突变工程改造，从而消除了 Fcγ 受体结合的可能性，进而消除了潜在的治疗介导的抗体依赖性增强作用。我们在感染 Zika 病毒前一天给非人类灵长类动物施用了这三种 nmAbs 的混合物，并证明 nmAbs 完全阻止了挑战后血清中的病毒血症。鉴于许多抗体在人类中具有出色的安全性，这里描述的鸡尾酒疗法可以迅速开发出来，以保护未感染的孕妇及其胎儿。
