通过泛汉氏病毒保护性抗体中和的结构和机制基础
Eva Mittler1, Alexandra Serris2, Emma S Esterman3
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Science translational medicine
|June 14, 2023
概括
一种新的抗体通过准汉塔病毒的融合蛋白来中和汉塔病毒. 该抗体的工程改进提高了它对致命安第斯病毒的有效性,提供了潜在的泛汉塔病毒治疗方法.
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:
- 汉塔病毒是由动物传播的,会引起人类的严重疾病.
- 目前还没有有效的疫苗或治疗汉塔病毒感染的方法.
研究的目的:
- 确定针对汉塔病毒的广泛中和抗体 (nAb) 活动的结构基础.
- 为了设计一个改进的nAb变体,增强治疗潜力.
主要方法:
- 从经验丰富的Puumala病毒供体中分离出一个单克隆抗体.
- 确定了与汉塔病毒 Gn/Gc 葡萄糖蛋白异构体结合的抗体的晶体结构.
- 设计了一种优化的nAb变体,以提高其有效性.
主要成果:
- 抗体的结构揭示了对保存的Gc融合循环和可变的Gn序列的识别,稳定了病毒融合复合体.
- 抗体的广泛中和活性是由其与保存表位的相互作用解释的.
- 在酸性pH下加速解离,对安第斯病毒的有效性有限;工程变体显示出更好的疗效.
结论:
- 抗体的作用机制涉及将Gn/Gc异构体锁定在预注射形状中.
- 抗体工程可以克服诸如pH依赖解离等局限性,增强治疗潜力.
- 优化的抗体代表了一种有前途的候选人,用于泛汉氏病毒治疗.
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