从先前存在的记忆B细胞中识别广泛抑制的流感神经aminidase抗体
Xin Wang1, Huihui Kong2, Bingxin Chu3
1Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, Center for Infectious Disease Research, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
Cell host & microbe
|December 31, 2024
概括
研究人员发现,在成年人中,预先存在的记忆B细胞准流感神经aminidase (NA). 这些细胞和衍生的抗体提供了对各种流感菌株的保护,为通用流感疫苗铺平了道路.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 疫苗学 疫苗学 疫苗学
背景情况:
- 开发一种通用流感疫苗需要识别广泛反应的B细胞和保存的表位.
- 流感神经氨基酶 (NA) 是通用流感疫苗战略的一个关键目标.
研究的目的:
- 在人类中调查先前存在的NA特异性记忆B细胞 (MBCs) 的存在和特征.
- 识别和表征新型单克隆抗体 (mAbs),以保护广泛的流感,向保存的NA表位.
主要方法:
- 利用流感神经氨基酶 (NA) 突变探针来分析人类MBC种群.
- 隔离和表征了三个NA广泛抑制单克隆抗体 (BImAbs).
- 使用冷电子显微镜 (cryo-EM) 确定了BImAb结合的结构基础.
主要成果:
- 预先存在的NA特异性MBC约占MBC总数的0.25%,并且是异质的.
- 确定了三种BImAbs能够抑制各种流感菌株的NA活性,包括H5N1.
- 结冷EM揭示了BImAbs向保存的NA酶口袋和相邻的表位,在小鼠模型中提供对H1N1和H5N1挑战的保护.
结论:
- 针对NA的广泛抑制前体MBC存在于健康成年人中.
- 基于NA的通用流感疫苗是一种可行的策略,利用这些前体细胞和已识别的BImAbs.
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