Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
J Virol. 2024 Oct 22;98(10):e0063824. doi: 10.1128/jvi.00638-24. Epub 2024 Sep 6.
Nipah virus (NiV) is a highly pathogenic paramyxovirus capable of causing severe respiratory and neurologic disease in humans. Currently, there are no licensed vaccines or therapeutics against NiV, underscoring the urgent need for the development of countermeasures. The NiV surface-displayed glycoproteins, NiV-G and NiV-F, mediate host cell attachment and fusion, respectively, and are heavily targeted by host antibodies. Here, we describe a vaccination-derived neutralizing monoclonal antibody, mAb92, that targets NiV-F. Structural characterization of the Fab region bound to NiV-F (NiV-F-Fab92) by cryo-electron microscopy analysis reveals an epitope in the DIII domain at the membrane distal apex of NiV-F, an established site of vulnerability on the NiV surface. Further, prophylactic treatment of hamsters with mAb92 offered complete protection from NiV disease, demonstrating beneficial activity of mAb92 . This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV.IMPORTANCENipah virus (NiV) is a highly lethal henipavirus (HNV) that causes severe respiratory and neurologic disease in humans. Currently, there are no licensed vaccines or therapeutics against NiV, highlighting a need to develop countermeasures. The NiV surface displays the receptor binding protein (NiV-G, or RBP) and the fusion protein (NiV-F), which allow the virus to attach and enter cells. These proteins can be targeted by vaccines and antibodies to prevent disease. This work describes a neutralizing antibody (mAb92) that targets NiV-F. Structural characterization by cryo-electron microscopy analysis reveals where the antibody binds to NiV-F to neutralize the virus. This study also shows that prophylactic treatment of hamsters with mAb92 completely protected against developing NiV disease. This work shows how targeting NiV-F can be useful to preventing NiV disease, supporting future studies in the development of vaccines and therapeutics.
尼帕病毒（NiV）是一种高致病性副粘病毒，能够导致人类严重的呼吸道和神经系统疾病。目前，尚无针对 NiV 的许可疫苗或疗法，这突显了开发应对措施的迫切需求。NiV 表面展示的糖蛋白 NiV-G 和 NiV-F 分别介导宿主细胞附着和融合，并且是宿主抗体的主要靶标。在这里，我们描述了一种针对 NiV-F 的疫苗衍生的中和单克隆抗体 mAb92。通过冷冻电镜分析对与 NiV-F 结合的 Fab 区域的结构表征揭示了 NiV-F 的 DIII 结构域中膜远端顶点上的一个表位，这是 NiV 表面上的一个既定脆弱部位。此外，用 mAb92 对仓鼠进行预防性治疗可完全防止 NiV 疾病，证明了 mAb92 的有益活性。这项工作为针对 NiV-F 开发针对 NiV 的疫苗和疗法提供了支持。
