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Updated: Jul 17, 2025

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通过获得低B细胞亲缘关系来吸引艾滋病毒疫苗目标

Larance Ronsard¹, Ashraf S Yousif¹, Faez Amokrane Nait Mohamed¹

¹The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA, 02139, USA.

Nature communications

|August 28, 2023

概括

这项研究揭示了如何扩展低亲和度B细胞受体 (BCRs) 来开发针对HIV的广泛中和抗体 (bnAbs). 身体突变 (SHM) 有助于目标获取,这表明发现新抗体表位的途径.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
疫苗开发疫苗开发

背景情况:

生殖系B细胞受体 (BCRs) 通常具有较低的亲和力,但对于开发针对HIV等病毒的广泛中和抗体 (bnAbs) 至关重要.
抗体亲和性选择是非同质化的,允许低亲和性B细胞克隆的生存,这些克隆可以用于疫苗标.

研究的目的:

研究是否可以扩展低亲和度B细胞克隆以准保存的疫苗表位,使用模仿人类抗体多样性和体质突变 (SHM) 的转基因小鼠.
探索一种免疫策略,将B细胞记忆集中在保存的表位上,例如HIV CD4结合部位 (CD4bs).

主要方法:

利用具有人类抗体多样性和SHM能力的转基因小鼠.
接种了简单单性HIV糖蛋白包膜免疫原体的免疫小鼠.
分析了B细胞反应,重点关注亲和力成熟和低亲和力BCR克隆的扩张.

主要成果:

开发了一种免疫疗法,成功地将B细胞记忆集中在HIV CD4结合部位 (CD4bs) 上.
观察到低亲和度BCR克隆的可复制扩张,在SHM中表现出公共模式.
发现SHM可以降低结合强度,促进这些低 afinity 克隆的目标获取.

结论:

允许性B细胞选择,特别是通过SHM扩展低亲和度克隆,可以使抗体表位的发现.
这种方法为开发广泛中和抗体 (bnAbs) 对抗艾滋病毒等具有挑战性的目标提供了潜在的战略.

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