华盛顿大学David Veesler研究小组取得一项新突破。他们提出了疫苗诱导抗体对马尔堡病毒的有效中和作用。这一研究成果于2025年11月12日发表在国际顶尖学术期刊《自然》上。

该课题组人员设计了一些突变，改善了融合前MARV糖蛋白（GP）外结构域三聚体的表达、热稳定性和免疫原性，GP是发育过程中中和抗体和疫苗的唯一靶点。该课题组研究人员发现了一种完全人源的泛马尔堡病毒单克隆抗体MARV16，它能广泛中和所有马尔堡病毒分离株以及Ravn病毒和德宏病毒，其效力比先前描述的抗体提高了40至100倍。

此外，MARV16对感染MARV的豚鼠提供治疗性保护。该课题组确定了MARV16结合的MARV GP的低温电镜结构，表明MARV16识别跨越GP1和GP2的抗原特异性表位，阻断受体结合并阻止病毒进入所需的构象变化。该课题组研究人员进一步揭示了MARV GP聚糖帽的结构，它屏蔽了受体结合位点（RBS），强调了与远亲丝状病毒GP在结构上的相似性。MARV16和先前鉴定的RBS定向抗体可以同时结合MARV GP。这些抗体鸡尾酒需要多种突变来逃避两种抗体的中和，为MARV疗法对病毒进化的适应性铺平了道路。MARV GP的稳定以及MARV16的发现为MARV的预防和治疗提供了新的选择。

据了解，马尔堡病毒（MARV）是一种丝状病毒，可引起严重且通常致命的出血热。尽管MARV爆发的频率越来越高，但没有疫苗或治疗方法获准用于人类。

附：英文原文

Title: Potent neutralization of Marburg virus by a vaccine-elicited antibody

Author: Addetia, Amin, Perruzza, Lisa, Sprouse, Kaitlin, Park, Young-Jun, McCallum, Matthew, Stewart, Cameron, Partini, Bianca, Brown, Jack T., Donati, Alessia, Culap, Katja, Balmelli, Alessio, Chawla, Bhavna, Kar, Swagata, Gazi, Michal, Alfson, Kendra, Goez-Gazi, Yenny, Carrion, Ricardo, Corti, Davide, Benigni, Fabio, Veesler, David

Issue&Volume: 2025-11-12

Abstract: Marburg virus (MARV) is a filovirus that causes a severe and often lethal hemorrhagic fever1,2. Despite the increasing frequency of MARV outbreaks, no vaccines or therapeutics are licensed for use in humans. Here, we designed mutations that improve the expression, thermostability, and immunogenicity of the prefusion MARV glycoprotein (GP) ectodomain trimer, which is the sole target of neutralizing antibodies and vaccines in development3–8. We discovered a fully human, pan-marburgvirus monoclonal antibody, MARV16, that broadly neutralizes all MARV isolates as well as Ravn virus and Dehong virus with 40 to 100-fold increased potency relative to previously described antibodies9. Moreover, MARV16 provides therapeutic protection in guinea pigs challenged with MARV. We determined a cryo-electron microscopy structure of MARV16-bound MARV GP showing that MARV16 recognizes a prefusion-specific epitope spanning GP1 and GP2, blocking receptor binding and preventing conformational changes required for viral entry. We further reveal the architecture of the MARV GP glycan cap, which shields the receptor binding site (RBS), underscoring architectural similarities with distantly related filovirus GPs. MARV16 and previously identified RBS-directed antibodies9–11 can bind MARV GP simultaneously. These antibody cocktails require multiple mutations to escape neutralization by both antibodies, paving the way for MARV therapeutics resilient to viral evolution. MARV GP stabilization along with the discovery of MARV16 advance prevention and treatment options for MARV.

DOI: 10.1038/s41586-025-09868-1

Source: https://www.nature.com/articles/s41586-025-09868-1