PDF(Pubmed)
Abstract：
Successful DNA vaccination generally requires the aid of either a viral vector within vaccine components or an electroporation device into the muscle or skin of the host. However, these systems come with certain obstacles, including limited transgene capacity, broad preexisting immunity in humans, and substantial cell death caused by high voltage pulses, respectively. In this study, we repurposed the use of an amphiphilic bioresorbable copolymer (ABC), called PLA-PEG, as a surface engineering agent that conciliates lipid nanoparticles (LNPs) between stability during preparation and biocompatibility post-vaccination. The LNP carrier can be loaded with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific DNA; in this form, the DNA-LNP is immunogenic in hamsters and elicits protective immunity following DNA-LNP vaccination against heterologous virus challenge or as a hybrid-type vaccine booster against SARS-CoV-2 variants. The data provide comprehensive information on the relationships between LNP composition, manufacturing process, and vaccine efficacy. The outcomes of this study offer new insights into designing next-generation LNP formulations and pave the way for boosting vaccine power to combat existing and possible emerging infectious diseases/pathogens.
摘要：
成功的DNA疫苗接种通常需要借助疫苗组分内的病毒载体或电穿孔装置进入宿主的肌肉或皮肤。然而,这些系统有一定的障碍，包括有限的转基因能力，在人类中广泛存在的免疫力，以及由高压脉冲引起的大量细胞死亡，分别。在这项研究中,我们重新利用了两亲性生物可吸收共聚物（ABC），称为PLA-PEG，作为表面工程剂，可在制备过程中的稳定性和疫苗接种后的生物相容性之间调节脂质纳米颗粒（LNP）。LNP载体可以装载严重急性呼吸综合征冠状病毒2（SARS-CoV-2）尖峰特异性DNA；以这种形式，DNA-LNP在仓鼠中具有免疫原性,并且在针对异源病毒攻击的DNA-LNP疫苗接种后或作为针对SARS-CoV-2变体的杂合型疫苗加强剂引发保护性免疫。这些数据提供了关于LNP组成之间关系的全面信息，制造过程，和疫苗功效。这项研究的结果为设计下一代LNP制剂提供了新的见解，并为提高疫苗能力以对抗现有和可能出现的传染病/病原体铺平道路。
