基于糖蛋白亚单元疫苗的结构设计,用于疹疫苗
Rebecca J Loomis1, Yen-Ting Lai1, Sun B Sowers2
1Vaccine Research Center, NIH, Bethesda, MD 20892.
概括
使用输血前F糖蛋白的新型型副单元疫苗显示出有前途. 这些工程免疫原体产生强大的中和抗体,对抗各种疹病毒基因型,潜在地提高免疫力或作为下一代疫苗.
科学领域:
- 病毒学和免疫学 病毒学和免疫学
- 疫苗开发 疫苗开发
- 结构生物学 结构生物学
背景情况:
- 麻疹病毒 (MuV) 仍然是一个全球公共卫生问题,尽管疫苗接种率很高,但仍导致疫情爆发.
- 免疫力下降和疫苗菌株与流通的野生型疹病毒之间的抗原漂移导致疫苗无效.
- 目前的麻疹,疹和红疹 (MMR) 疫苗可能需要增强或下一代替代品.
研究的目的:
- 根据基于结构的设计,设计新型疹病毒亚单元候选疫苗.
- 评估稳定前F (Pre-F) 和仿制前F/HN免疫原的免疫性和交叉中和潜力.
- 描述这些新型免疫原引起的中和抗体反应.
主要方法:
- 基于结构的设计被用来设计疹融合 (F) 糖蛋白,其稳定在预注射形状 (Pre-F).
- 创建了一个含有Pre-F和麻风血素神经氨基酶 (HN) 相关的嵌合性免疫原.
- 确定了 mumps Pre-F 的晶体结构;产生了单克隆抗体,并对不同类型的型病毒基因型中和活性进行了表征.
主要成果:
- 在小鼠中,PRE-F抗原和虚构的PRE-F/HN免疫原都产生了强大的交叉反应性中和抗体标位,对抗疹病毒基因型A,G和H.
- 晶体结构证实了疹前期F的稳定.
- 隔离的抗体证明了各种型病毒基因型的中和,向Pre-F和HN糖蛋白上不同的抗原位点.
结论:
- 工程性疹Pre-F和模拟性Pre-F/HN免疫原是有效的诱导广泛的交叉中和抗体反应.
- 这些新型免疫原体代表了增强现有的MMR诱导免疫力或作为下一代疹疫苗的有希望的候选人.
- 进一步的发展可能会导致在高度免疫的人群中改善疹疫情的控制.
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