用疫苗诱导的抗原结合热点开发广泛的HIV中和
Rui Kong1, Hongying Duan1, Zizhang Sheng2
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Cell
|July 27, 2019
概括
使用HIV-1融合 (FP) 产生大致中和抗体 (bNAbs). 这些抗体向保存区域,增强多种HIV-1菌株的中和.
科学领域:
- 免疫学
- 病毒学
- 疫苗开发
背景情况:
- 通过疫苗接种产生广泛中和抗体 (bNAbs) 对抗各种HIV-1菌株仍然是一个重大挑战.
- 了解诱导bNAbs的机制对于有效的HIV疫苗设计至关重要.
研究的目的:
- 在接种疫苗的中识别,描述和跟踪针对HIV-1融合的抗体系.
- 确定使用FP可以诱导广泛中和抗体 (bNAbs).
主要方法:
- 用FP载体构造物和封膜 (Env) 增剂对进行疫苗接种.
- 对抗体系的遗传和结构分析.
- 对B细胞进行分析以追踪抗体的启动和扩张.
- 对各种HIV-1菌株的抗体中和范围的评估.
主要成果:
- 确定并追踪了针对FP的五种中和抗体 (Ab) 血统.
- 两种基因表现出可复制的广泛中和,对208种不同的HIV-1菌株的59%有效.
- FP载体启动并扩展了所有五种谱系,Env-trimer增强诱导交叉反应中和.
- 由FP引发的ABS显示了聚焦于FP的结合能量热点,与仅Env-trimer免疫的ABS不同.
结论:
- 使用像HIV-1 FP这样的保护子区域可以诱导在目标部位具有结合能量热点的抗体.
- 这种原始化策略导致能够对各种HIV-1菌株进行广泛中和的抗体.
- 针对FP的bNAbs是HIV疫苗开发的一个有希望的途径.
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