一种强有力的中和和保护的人类抗体,针对RSV和hMPV融合糖蛋白V的抗原位V
Alexandra A Abu-Shmais1,2, Luqiang Guo3, Ahmed Magady Khalil4,5
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
bioRxiv : the preprint server for biology
|November 18, 2024
概括
研究人员发现了一种新的抗体,5-1,可以中和人类呼吸道同胞病毒 (RSV) 和人类甲肺病毒 (hMPV). 这种交叉反应性抗体在小鼠中提供了保护,突出了治疗这些常见病毒感染的潜力.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 人类呼吸道同胞性病毒 (RSV) 和人类甲肺病毒 (hMPV) 在脆弱群体中引起重大疾病和死亡.
- 融合 (F) 糖蛋白是对抗RSV和hMPV抗体中和的关键目标.
- 在F糖蛋白中的结构相似性允许在特定的抗原位点 (III,IV,V) 进行交叉中和反应.
研究的目的:
- 确定针对RSV和hMPVF糖蛋白的新型交叉反应性抗体.
- 描述已识别的抗体的中和能力和保护功效.
- 阐明交叉反应的结构基础,用于治疗的发展.
主要方法:
- LIBRA-seq用于查对RSV和hMPV都具有反应性的人类抗体.
- 进行了体外中和试验,以评估对各种病毒菌株的抗体强度.
- 用小鼠挑战模型来评估抗体赋予的体内保护.
- 结构分析确定了交叉中和的结合表位和机制.
主要成果:
- 确定了5种对RSV和hMPV具有交叉反应性的人类抗体.
- 抗体5-1证明了对所有测试的RSV和hMPV亚组的强烈中和.
- 在小鼠模型中,5-1抗体对RSV和hMPV的挑战提供了显著的保护.
- 结构研究表明,5-1结合了F糖蛋白上跨越Ø,II和V位点的新型表位.
结论:
- 抗体5-1代表了对RSV和hMPV的强有力的交叉中和剂.
- 这些发现定义了RSV和hMPV F糖蛋白之间的抗体交叉反应的新机制.
- 5-1抗体对抗RSV和hMPV感染的治疗应用有希望.
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