识别所有流感A亚型的抗体的结构和功能分析
Nicole L Kallewaard1, Davide Corti2, Patrick J Collins3
1Department of Infectious Disease and Vaccines, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
Cell
|July 26, 2016
概括
一种新的人类单克隆抗体,MEDI8852,通过向血凝素蛋白的保存区域,有效地中和所有流感A亚型. 与现有的治疗方法相比,这种广泛的抗体显示出更高的疗效和治疗窗口.
科学领域:
- 免疫学
- 病毒学
- 结构生物学
背景情况:
- 由于抗原漂移,流感病毒构成持续的威胁,导致免疫逃避和疫苗有效性的降低.
- 由于流感菌株的快速演变, 现有的治疗方法和疫苗面临挑战.
研究的目的:
- 针对所有流感A血凝素 (HA) 亚型有效的宽谱人类单克隆抗体 (mAb) 的分离和鉴定.
- 阐明抗体广泛的中和活性和治疗潜力的结构基础.
主要方法:
- 人类单克隆抗体MEDI8852的分离和表征.
- 在小鼠和鱼模型中进行的体内疗效研究.
- 与流感HA蛋白复合的抗体Fab片段的晶体分析.
主要成果:
- 在所有甲型流感HA亚型中,MEDI8852具有强大和广泛的中和作用.
- 结构分析显示HA融合域的保存区域有一个独特的结合表位.
- 在临床前模型中,该抗体表现出比oseltamivir更高的疗效和更宽的治疗窗口.
结论:
- 对于A型流感病毒感染,MEDI8852是一种有前途的广泛免疫疗法.
- 它独特的结合机制和高强度为流感的发展提供了潜在的解决方案.
- 对于人类的治疗应用,MEDI8852的进一步开发是有必要的.
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