一种类似于核体的狂犬病病毒纳米结构疫苗,基于双离子脂质纳米粒子
Zhixiao Zhang1,2, Jingjing Zhang1,2, Changyong Mu1,2
1Weirui Biotechnology (Kunming) Co., Ltd., Ciba Biotechnology Innovation Center, Kunming 650000, China.
Vaccines
|December 24, 2025
概括
一种使用类似核体的纳米结构 (NLS) 的新型狂犬病疫苗,同时提供G-mRNA和RABV-N,显示出有前途. 这种双抗原NLS疫苗在两剂后,在小鼠中提供了对狂犬病的完整保护.
科学领域:
- 纳米技术在疫苗开发中的作用
- 病毒学和免疫学 病毒学和免疫学
- 分子生物学和蛋白质表达
背景情况:
- 狂犬病病毒 (RABV) 导致人类每年显著的死亡率,目前的疫苗有局限性.
- 现有的非活化疫苗 (INV) 的产量和免疫性有限.
- 一个新的基于双质脂质纳米粒子 (LNP) 的核体样纳米结构 (NLS) 被设计出来.
研究的目的:
- 开发和评估一种针对狂犬病的新型双抗原NLS疫苗.
- 评估NLS疫苗的免疫性和保护性疗效.
- 研究NLS疫苗对MHC-I/II通路的作用.
主要方法:
- 设计了一种双离子LNP,以共同封装RABV G-mRNA和RABV-N蛋白质.
- 使用封装效率,DLS,PDI,泽塔潜力和TEM来描述疫苗的质量.
- 在小鼠中通过ELISA,RFFIT,ELISPOT和qPCR评估免疫性,随后进行病毒挑战.
主要成果:
- 该NLS疫苗实现了高封装效率和最佳的物理化学特性.
- 一次NLS剂量迅速诱导中和抗体 (nAb),两次剂量达到~1000 IU mL-1.1,达到峰值.
- 在小鼠中,NLS疫苗给出了100%的存活率,具有强大的细胞免疫力,没有病毒反弹.
结论:
- 双抗原NLS疫苗有效地激活MHC-I/II通路,产生快速的,高位的nAb和强大的T细胞反应.
- 在小鼠模型中,NLS疫苗的两剂方案提供了对狂犬病的完整保护.
- 该NLS平台代表了下一代狂犬病疫苗的有希望的候选人.
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