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狂犬病糖蛋白工程用于改善稳定性和表达

Solomon English¹, Sofiya Fedosyuk¹, Francisco Orliacq¹

¹Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

|July 27, 2025

概括

开发新的狂犬病疫苗对于可访问性至关重要. 研究人员对狂犬病病毒糖蛋白 (RVG) 进行了改造,以提高疫苗免疫性,但发现野生型RVG足以用于小鼠当前的mRNA和腺病毒平台.

科学领域:

疫苗学疫苗学疫苗学
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

目前的狂犬病疫苗很昂贵,需要多剂量,限制了全球的使用.
开发新型,低成本的疫苗,引起对狂犬病病毒糖蛋白 (RVG) 的强有力的免疫反应,是优先事项.

研究的目的:

研究结构引导的抗原工程和转基因磁带优化,以提高狂犬病疫苗免疫性.
评估针对狂犬病病毒增强表达,稳定性和保护性抗体反应的新型疫苗结构.

主要方法:

评估了12个候选转基因磁带设计,包括代优化和共同表达策略.
在低pH下选了72个RVG突变结构以检测体外表达和融合前稳定性.
在小鼠中使用mRNA疫苗平台测试野生型RVG和突变构造物的免疫性.

主要成果:

子优化改善了体外表达,但没有提高免疫性.
突变结构表现出增强的表达和/或稳定性,特定的双重突变 (L271Q + H419L) 显示出最大的表达增加.
与mRNA疫苗中的野生型RVG相比,无论是工程RVG突变还是磁带优化都没有提高免疫性.

结论:

虽然某些突变增强了RVG表达和稳定性,但它们并没有转化为mRNA疫苗中免疫性改善.
全长野生型RVG似乎足够稳定,并在腺病毒和mRNA狂犬病疫苗中表达出最佳免疫性.
工程化RVG突变可能对未来的蛋白质子单元疫苗开发有潜力.

关键词:

亚地诺病毒是亚地诺病毒.狂犬病病毒的葡萄糖蛋白是狂犬病病毒的糖蛋白.结构导向设计是指导结构的设计.亚单位疫苗亚单位疫苗它们是mRNARNA.

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