Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo–electron microscopy (cryo-EM) structures of prefusion F alone [2.1-angstrom (Å) resolution], F complexed with a fusion-inhibitory peptide (2.3-Å resolution), F complexed with the neutralizing and protective monoclonal antibody (mAb) 77 (2.6-Å resolution), and an additional structure of postfusion F (2.7-Å resolution). In vitro assays and examination of additional EM classes show that mAb 77 binds prefusion F, arrests F in an intermediate state, and prevents transition to the postfusion conformation. These structures shed light on antibody-mediated neutralization that involves arrest of fusion proteins in an intermediate state.

中文翻译：

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中和抗体可防止麻疹病毒融合蛋白融合后转变


麻疹病毒 (MeV) 构成的公共卫生威胁随着普通人群疫苗覆盖率的下降以及无法接种疫苗的免疫功能低下人群的增加而不断升级。目前还没有批准的 MeV 治疗方法。针对病毒融合的中和抗体是一种潜在的治疗方法，但尚未进行结构表征或推进临床使用。我们展示了单独的预融合 F [2.1 埃 (Å) 分辨率]、F 与融合抑制肽复合物（2.3-Å 分辨率）、F 与中和和保护性单克隆抗体复合物的冷冻电子显微镜 (cryo-EM) 结构(mAb) 77（2.6-Å 分辨率），以及融合后 F 的附加结构（2.7-Å 分辨率）。体外测定和其他 EM 类别的检查表明，mAb 77 结合融合前 F，将 F 阻止在中间状态，并防止向融合后构象的转变。这些结构揭示了抗体介导的中和作用，涉及将融合蛋白阻滞在中间状态。