通过疫苗引起的抗体对马尔堡病毒进行强有力的中和
Amin Addetia1, Lisa Perruzza2, Kaitlin Sprouse1,3
1Department of Biochemistry, University of Washington, Seattle, WA, USA.
Nature
|November 12, 2025
概括
研究人员开发了一种稳定的马尔堡病毒糖蛋白 (GP),并发现了MARV16,这是一种强大的抗体,可以中和马尔堡病毒 (MARV) 并防止致命的感染. 这促进了MARV疾病的预防和治疗选择.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 马尔堡病毒 (MARV) 导致严重的出血热, 没有授权的疫苗或治疗药物.
- 在疫苗和中和抗体中,MARV葡萄糖蛋白 (GP) 外域三元体是关键的标.
- 目前的MARV治疗方法有限,需要开发新的治疗策略.
研究的目的:
- 改善马尔堡病毒糖蛋白 (GP) 的表达,稳定性和免疫性.
- 发现用于广泛中和MARV的新型单克隆抗体.
- 阐明MARV中和治疗的结构基础.
主要方法:
- 蛋白质工程稳定了MARV预注射GP的ectodomain分离器.
- 发现和描述泛马堡病毒单克隆抗体 (MARV16).
- 低温电子显微镜 (cryo-EM) 来确定与MARV16结合的MARVGP的结构.
- 在MARV挑战的几内亚猪模型中进行的体内疗效研究.
主要成果:
- 设计了具有增强表达和热稳定的稳定MARVGP剪裁器.
- 发现了一种强大的人类单克隆抗体,MARV16,它在很大程度上可以中和MARV分离物,Ravn病毒和Dehong病毒.
- 在感染MARV的豚鼠中,MARV16已显示出治疗效果.
- 冷EM检测显示MARV16结合了输血前特定的表位,阻断了病毒的进入.
- 可以将MARV16和现有的抗体结合使用,因此需要多个突变才能脱离病毒,这表明病毒对病毒进化具有抵抗力.
结论:
- 稳定MARVGP和发现MARV16代表了MARV对抗措施的重大进展.
- MARV16为马尔堡病毒病提供了一个有前途的治疗候选药物.
- 组合抗体治疗策略可以克服病毒耐药性,为强大的MARV疗法铺平道路.
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