DNA vaccine is an attractive immune platform for the prevention and treatment of infectious diseases, but existing disadvantages limit its use in preclinical and clinical assays, such as weak immunogenicity and short half-life. Here, we reported a novel liposome-polymer hybrid nanoparticles (pSFV-MEG/LNPs) consisting of a biodegradable core (mPEG-PLGA) and a hydrophilic shell (lecithin/PEG-DSPE-Mal 2000) for delivering a multi-epitope self-replication DNA vaccine (pSFV-MEG). The pSFV-MEG/LNPs with optimal particle size (161.61 ± 15.63 nm) and high encapsulation efficiency (87.60 ± 8.73%) induced a strong humoral (3.22-fold) and cellular immune responses (1.60-fold) compared to PBS. Besides, the humoral and cellular immune responses of pSFV-MEG/LNPs were 1.58- and 1.05-fold than that of pSFV-MEG. All results confirmed that LNPs was a very promising tool to enhance the humoral and cellular immune responses of pSFV-MEG. In addition, the rational design and delivery platform can be used for the development of DNA vaccines for other infectious diseases.

DNA疫苗是预防和治疗传染病的一个有吸引力的免疫平台，但现有的缺点限制了它在临床前和临床检测中的应用，例如免疫原性弱和半衰期短。在这里，我们报道了一种新型脂质体-聚合物杂化纳米粒子 (pSFV-MEG/LNPs)，由可生物降解的核心 (mPEG-PLGA) 和亲水壳 (lecithin/PEG-DSPE-Mal 2000) 组成，用于递送多表位自-复制 DNA 疫苗 (pSFV-MEG)。与 PBS 相比，具有最佳粒径 (161.61 ± 15.63 nm) 和高封装效率 (87.60 ± 8.73%) 的 pSFV-MEG/LNP 诱导了强烈的体液免疫反应（3.22 倍）和细胞免疫反应（1.60 倍）。此外，pSFV-MEG/LNPs 的体液和细胞免疫反应分别是 pSFV-MEG 的 1.58 倍和 1.05 倍。所有结果证实，LNPs 是一种非常有前途的工具，可以增强 pSFV-MEG 的体液和细胞免疫反应。此外，合理的设计和交付平台可用于其他传染病的DNA疫苗的开发。