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修改线性DNA疫苗的非编码区域,以探索表达和炎症在免疫性中的相互作用

David C Stirling¹, Maria de Miguel Ferrer^1,2, Sungwon Kim²

¹Department of Infectious Disease, Imperial College London, London, UK.

Human vaccines & immunotherapeutics

|January 20, 2025

概括

优化DNA疫苗设计对于提高免疫性至关重要. 封闭的线性DNA平台中的增强剂和DNA向序列可以促进小鼠的抗原表达和免疫反应,为未来的疫苗开发提供了一个有希望的途径.

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:

随着COVID-19的流行,人们越来越需要适应性疫苗技术,RNA疫苗越来越受欢迎.
与RNA疫苗相比,DNA疫苗在制造,储存和潜在的减少反应性方面具有优势.
从历史上看,DNA疫苗在大型动物和人体试验中显示出有限的免疫性,需要优化策略.

研究的目的:

调查修改非编码5'区域对非细胞生产的封闭线性DNA平台 (DoggyboneTM DNA) 免疫性的影响.
评估增强剂序列,DNA向序列 (DTS) 和CpG基因在调节免疫反应中的作用.
为了区分DNA构造免疫传感与抗原表达对疫苗疗效的影响.

主要方法:

使用小鼠模型评估DNA疫苗结构与修改的非编码5'区域.
构造的狗骨TMDNA (dbDNATM) 编码流感病毒血质素 (HA),SARS-CoV-2尖峰和eGFP.
评估抗原表达水平和免疫反应,包括同时服用CpG寡氧核酸 (ODN) 的影响.

主要成果:

增强序列和DNA向序列 (DTS) 显著增加了流感HA表达和增强了免疫反应.
添加额外的CpG基因并没有给免疫系统带来任何额外的益处.
非编码序列的影响是抗原特异性的,在流感HA,SARS-CoV-2 Spike和eGFP构造中显示出各种效应.
分离免疫传感和抗原表达表明,在使用CpG ODNs时,减少表达与较高的炎症导致相当的免疫性.

结论:

修改非编码的5'区域,特别是结合增强剂和DTS,可以提高DNA疫苗的免疫性.
CpG图案并不普遍增强DNA疫苗的免疫性.
了解DNA结构特征,抗原表达和先天免疫感应之间的复杂相互作用对于开发保护性DNA疫苗至关重要.

关键词:

在 COVID-19 疫情中,在CpG中使用.疫苗疫苗疫苗疫苗这是一种炎症炎症炎症炎症.流感流感流感流感流感

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