弗拉维病毒E蛋白疫苗的合理设计优化了免疫性,并减轻了抗体依赖增强风险
Yimeng Wang1,2, Andrey Galkin1,3, Xiaoran Shang1,3
1Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.
Nature communications
|December 22, 2025
概括
新的弗拉维病毒疫苗使用一种新的策略来预防疾病增强和提高疗效. 这种方法隐藏了关键的病毒表位,提供了对寨卡和登革热等病毒的更好的保护.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 疫苗开发 疫苗开发
背景情况:
- 弗拉维病毒对全球健康构成重大风险,导致广泛的疾病和死亡.
- 现有的疫苗可能导致抗体依赖增强 (ADE) 或对相关的黄病毒的疗效降低.
研究的目的:
- 开发一种新的弗拉维病毒疫苗策略,最大限度地减少ADE并提高保护功效.
- 为了设计一种基于寨卡病毒 (ZIKV) 和隐藏的表位体的黄病毒候选疫苗 (CC_FLE sE).
主要方法:
- 引入G5C/G102C突变到flavivirus包裹 (E) 糖蛋白中,以促进二元化并隐藏融合循环表观 (FLE).
- 通过生物化学,抗原和结构分析,在多个黄病毒中验证了工程E蛋白.
- 在小鼠模型中测试了ZIKV CC_FLE sE候选疫苗,包括具有人类免疫球蛋白位点的小鼠模型.
主要成果:
- CC_FLE sE候选疫苗在雌性小鼠中显示出对ZIKV挑战的显著保护.
- 这种疫苗可以预防由登革热病毒引起的ADE,而登革热病毒是一种相关的黄状病毒.
- 在人性化的小鼠模型中,CC_FLE sE引起了针对ZIKV表位体的强大的中和抗体,包括E-二分体依赖表位体 (EDE).
结论:
- CC_FLE sE 策略有效地隐藏了易发生ADE的表位,降低了疾病恶化的风险.
- 这种方法在人类的B细胞中引起保护性抗体反应.
- CC_FLE sE代表了开发安全有效的黄病毒疫苗的有希望的平台.
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