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Jon M Steichen^1,2,3, Ying-Cing Lin⁴, Colin Havenar-Daughton^3,5

¹Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Science (New York, N.Y.)

|November 2, 2019

概括

开发针对罕见的B细胞前体的新型免疫原体是诱导广泛中和抗体 (bnAbs) 的关键. 这种策略使免疫系统产生保护性的bnAbs,克服了HIV疫苗开发中的一个主要障碍.

科学领域:

免疫学
疫苗学
结构生物学

背景情况:

诱导针对艾滋病毒的广泛中和抗体 (bnAbs) 是疫苗开发的一个重大挑战.
许多bnAbs在很大程度上依赖抗体重链互补性决定区域3 (HCDR3),因为它们具有强大的中和活性,这对生殖线向策略构成了障碍.

研究的目的:

识别和开发能够启动免疫系统生成特定类型的HIV bnAbs的新型免疫原体.
通过采用由谱导向的生殖系向方法来克服HCDR3主导的bnAbs所带来的挑战.

主要方法:

使用超深度人类抗体测序来识别潜在的抗体前体.
设计和开发基于HIV包膜的免疫原体.
在B细胞启动的小鼠模型中测试免疫原效.
使用原始人类B细胞进行了ex vivo查.

主要成果:

确定了一组具有主导性HCDR3接触的bnAbs潜在抗体前体.
在小鼠中开发出成功启动罕见bnAb前体B细胞的免疫原体.
证明这些免疫原与一系列潜在的bnAb前体B细胞结合.

结论:

基因谱导向向方法为诱导HIV bnAbs提供了可行的框架.
这一策略有可能应用于针对其他病原体的HCDR3主导抗体的疫苗开发.

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