针对组合抗原蛋白mRNA疫苗接种的病毒样结构
Jingjing Zhang1,2, Yanmei Li1, Fengyuan Zeng1
1Weirui Biotechnology (Kunming) Co., Ltd, Ciba Biotechnology Innovation Center, Kunming, China.
Nature nanotechnology
|May 27, 2024
概括
这项研究引入了一种新的类似病毒的粒子疫苗系统,可以有效地传递mRNA和蛋白质抗原. 这种增强的输送系统显著提高了抗体反应,为改善针对病毒威胁的疫苗接种策略提供了有希望的方法.
科学领域:
- 免疫学和疫苗学 免疫学和疫苗学
- 纳米技术在医学中的应用
- 病毒学和传染病学.
背景情况:
- 有效的疫苗接种需要先进的抗原输送系统和强大的免疫激活.
- 当前的疫苗技术在优化抗原呈现和引起广泛的免疫反应方面面临着挑战.
- SARS-CoV-2 变种的出现凸显了适应性和强大的疫苗平台的需要.
研究的目的:
- 开发和评估一种基于脂质纳米颗粒的新型病毒样颗粒 (VLP) 系统,用于增强抗原递送.
- 调查VLP系统能够提供mRNA和蛋白质抗原的能力,特别针对SARS-CoV-2变种.
- 评估与单组分疫苗相比,联合mRNA-蛋白VLP疫苗产生的免疫反应.
主要方法:
- 工程化脂质纳米颗粒与SARS-CoV-2尖端蛋白 (Omicron BA.1 S1) 装饰,以形成VLPs.
- 利用VLP共同传递编码不同SARS-CoV-2变体 (XBB.1) 的S1蛋白的mRNA和S1蛋白本身.
- 通过ACE2和DC-SIGN受体评估了VLP与人类呼吸道上皮细胞和巨细胞的相互作用.
- 通过受体结合评估了巨细胞和树突细胞的激活.
- 用VLP系统,单独mRNA或单独蛋白质接种疫苗后,在BALB/c小鼠中测量了抗体反应.
主要成果:
- 该VLP系统成功地携带并传递了mRNA和蛋白质抗原.
- 在VLP上的表面S1蛋白促进了向传递,并增强了特定免疫细胞中的mRNA表达.
- 受体结合 (ACE2,DC-SIGN) 由表面S1蛋白激活的巨细胞和树突细胞介导.
- 与单价mRNA或蛋白质疫苗相比,组合mRNA-蛋白质VLP疫苗在小鼠中引起了显著更高的抗体反应.
- 免疫反应机制建议交叉呈现给多种树突细胞子集,弥合先天性和适应性免疫.
结论:
- 开发的VLP系统代表了一种有效的平台,可以同时提供mRNA和蛋白质抗原,从而提高疫苗的疗效.
- 通过特定的受体相互作用,有针对性的输送和免疫细胞激活有助于强大的免疫反应.
- 这一战略有望开发下一代针对SARS-CoV-2变种和潜在的其他传染病的疫苗.
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