一个人类单克隆抗体结合在脊髓灰质炎受体结合部位内,以中和所有三种血清型
Andrew J Charnesky1,2, Julia E Faust3, Hyunwook Lee2,3
1Molecular, Cellular, and Integrative Biosciences Program, The Pennsylvania State University, University Park, PA, USA.
Nature communications
|October 10, 2023
概括
一种新的人类单克隆抗体9H2通过阻断病毒受体结合部位来中和所有三种脊髓灰质炎病毒血清型. 这一发现为消除脊髓灰质炎病毒的努力提供了一个有希望的抗病毒策略.
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:
- 全球脊髓灰质炎病毒的根除正在进行中,需要新型疫苗和抗病毒药物.
- 人类单克隆抗体9H2证明了所有三种脊髓灰质炎病毒血清型的中和.
研究的目的:
- 为了绘制单克隆抗体9H2.2的表位.
- 阐明9H2中和抗脊髓灰质炎病毒的结构基础.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定9H2 Fab-脊髓灰质炎病毒复合物的近原子结构.
- 9H2与脊髓灰质炎病毒受体 (PVR) 之间的竞争结合测定.
主要成果:
- 9H2以类似的方式在所有三种脊髓灰质炎病毒血清型中结合了保存的位点.
- 9H2结合部位与体"峡谷"中的PVR结合部位重叠.
- 9H2结合抑制了脊髓灰质炎病毒受体相互作用,从而中和了病毒.
结论:
- 单克隆抗体9H2通过竞争性抑制PVR结合来中和脊髓灰质炎病毒.
- 保存的结合部位和交叉血清型中和使9H2成为一种强大的抗病毒候选者.
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