近日，
研究人员表示，麻疹病毒（MeV）是一种公共卫生威胁，随着疫苗在普通人群中的覆盖率下降以及无法接种疫苗的免疫力低下人群的增加，这种威胁也在不断升级。目前还没有针对MeV的获批疗法。以病毒融合为靶点的中和抗体是一种潜在的治疗方法，但其结构特征尚未确定，也尚未应用于临床。
研究人员展示了单独融合前F的冷冻电镜（cryo-EM）结构（2.1Å分辨率）、F与融合抑制肽复合物的结构（2.3Å埃分辨率）、F与中和保护性单克隆抗体（mAb）77复合物的结构（2.6Å分辨率）以及融合后F的附加结构（2.7Å分辨率）。体外试验和其他EM类检测表明，mAb 77能结合前融合F，使F停滞在中间状态，并阻止其过渡到融合后构象。这些结构揭示了抗体介导的中和作用，其中涉及将融合蛋白阻滞在中间状态。
附：英文原文
Title: A neutralizing antibody prevents postfusion transition of measles virus fusion protein
Author: Dawid S. Zyla, Roberta Della Marca, Gele Niemeyer, Gillian Zipursky, Kyle Stearns, Cameron Leedale, Elizabeth B. Sobolik, Heather M. Callaway, Chitra Hariharan, Weiwei Peng, Diptiben Parekh, Tara C. Marcink, Ruben Diaz Avalos, Branka Horvat, Cyrille Mathieu, Joost Snijder, Alexander L. Greninger, Kathryn M. Hastie, Stefan Niewiesk, Anne Moscona, Matteo Porotto, Erica Ollmann Saphire
Issue&Volume: 2024-06-28
Abstract: 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 () resolution], F complexed with a fusion-inhibitory peptide (2.3- resolution), F complexed with the neutralizing and protective monoclonal antibody (mAb) 77 (2.6- resolution), and an additional structure of postfusion F (2.7- 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.
DOI: adm8693
Source: https://www.science.org/doi/10.1126/science.adm8693