病毒受体结合部位抗体具有不同的生殖系起源
Aaron G Schmidt1, Matthew D Therkelsen1, Shaun Stewart2
1Laboratory of Molecular Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell
|May 12, 2015
概括
新的疫苗策略可以通过向受体结合部位 (RBS) 等保存区域来产生对不断演变的病毒的持久免疫力. 这项研究确定了许多可以结合保存的病毒表位体的抗体,从而提供广泛的保护.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 开发针对快速演变的病原体的疫苗需要产生针对保存表位的抗体,以获得持久的免疫力.
- 病毒表面蛋白质的受体结合部位 (RBS) 是一个关键的保存表位,被中和抗体准.
研究的目的:
- 识别能够识别快速演化病原体的保存受体结合位点 (RBS) 的抗体.
- 描述RBS定向抗体的结构基础和生殖系起源.
主要方法:
- 设计了一种基于流感病毒RBS定向抗体的特征动机,以寻找类似的抗体.
- 选疫苗接种者的抗体库,以确定候选抗体.
- 确定了与病毒抗原复合的已识别的抗体的结晶结构.
主要成果:
- 从三个接种疫苗的人身上鉴定出100多种候选抗体,这些抗体由11种不同的VH基因编码.
- 晶体结构显示,这些抗体模仿酸通过重链第三补充性确定区域二结合于血凝素RBS.
- 抗体接触到保存的RBS残留物,但在外围接触方面有所不同,这表明当多个抗体存在时,病毒逃生潜力降低.
结论:
- 不同的生殖系起源和亲和成熟路径可以导致类似的RBS识别模式.
- 旨在引起RBS导向反应的免疫原可以吸引广泛的B细胞点,促进强大且潜在的长期免疫力.
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