对抗SFTSV的广泛中和抗体的分子机制和结构引导的人性化
Pinyi Yang1, Xiaoli Wu2, Hang Shang1
1State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, China.
PLoS pathogens
|September 25, 2024
概括
一种新型抗体,mAb 40C10,通过将保存的表位蛋白与其糖蛋白结合来向严重发烧与血小板缩小综合征病毒 (SFTSV). 人性化版本显示出强大的中和活性和对SFTSV的治疗潜力.
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:
- 严重发烧与血小板缩小综合征病毒 (SFTSV) 是一种致命的传播病原体.
- SFTSV外糖蛋白介导宿主细胞的进入.
- 一个先前确定的抗体,mAb 40C10,显示广泛的中和,但其机制尚不清楚.
研究的目的:
- 阐明mAb 40C10对SFTSV的中和的结构基础.
- 为了确定广谱抗病毒策略的保存表位.
- 为潜在的临床用途开发人性化的抗体.
主要方法:
- 对SFTSV Gn-mAb 40C10复合物的高分辨率结构分析.
- 深入的结构和序列分析.
- 抗体的人性化和特征化.
- 在小鼠模型中的体内疗效研究.
主要成果:
- 在SFTSV Gn头部域 (域I) 上发现了一种新的结合表位.
- mAb 40C10结合位点在SFTSV基因型和相关病毒中保持.
- 人性化的mAb 40C10变种保留了强大的中和活性,其中一个达到皮科莫尔IC50值.
- 在小鼠模型中证明了治疗和保护作用.
结论:
- 这项研究揭示了mAb 40C10广泛中和的分子机制.
- 在SFTSV Gn上保存的表位为疫苗和药物开发提供了一个有希望的目标.
- 人性化抗体提供了针对SFTSV感染的可行的治疗策略.
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