Zhang Wanyue, Pfeifle Annabelle, Lansdell Casey, Frahm Grant, Cecillon Jonathon, Tamming Levi, Gravel Caroline, Gao Jun, Thulasi Raman Sathya N, Wang Lisheng, Sauve Simon, Rosu-Myles Michael, Li Xuguang, Johnston Michael J W
Centre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada and World Health Organization Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON K1A 0K9, Canada.
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Vaccines (Basel). 2023 Oct 11;11(10):1580. doi: 10.3390/vaccines11101580.
In recent years, lipid nanoparticles (LNPs) have emerged as a revolutionary technology for vaccine delivery. LNPs serve as an integral component of mRNA vaccines by protecting and transporting the mRNA payload into host cells. Despite their prominence in mRNA vaccines, there remains a notable gap in our understanding of the potential application of LNPs for the delivery of DNA vaccines. In this study, we sought to investigate the suitability of leading LNP formulations for the delivery of plasmid DNA (pDNA). In addition, we aimed to explore key differences in the properties of popular LNP formulations when delivering either mRNA or DNA. To address these questions, we compared three leading LNP formulations encapsulating mRNA- or pDNA-encoding firefly luciferase based on potency, expression kinetics, biodistribution, and immunogenicity. Following intramuscular injection in mice, we determined that RNA-LNPs formulated with either SM-102 or ALC-0315 lipids were the most potent (all -values < 0.01) and immunogenic (all -values < 0.05), while DNA-LNPs formulated with SM-102 or ALC-0315 demonstrated the longest duration of signal. Additionally, all LNP formulations were found to induce expression in the liver that was proportional to the signal at the injection site (SM102: r = 0.8787, < 0.0001; ALC0315: r = 0.9012, < 0.0001; KC2: r = 0.9343, < 0.0001). Overall, this study provides important insights into the differences between leading LNP formulations and their applicability to DNA- and RNA-based vaccinations.
近年来，脂质纳米颗粒（LNPs）已成为一种用于疫苗递送的革命性技术。LNPs通过保护和将mRNA有效载荷转运到宿主细胞中，成为mRNA疫苗的一个重要组成部分。尽管它们在mRNA疫苗中很突出，但我们对LNPs在DNA疫苗递送方面潜在应用的理解仍存在显著差距。在本研究中，我们试图研究主要LNP制剂用于递送质粒DNA（pDNA）的适用性。此外，我们旨在探索流行LNP制剂在递送mRNA或DNA时性质的关键差异。为了解决这些问题，我们基于效力、表达动力学、生物分布和免疫原性，比较了三种封装编码萤火虫荧光素酶的mRNA或pDNA的主要LNP制剂。在小鼠肌肉注射后，我们确定用SM-102或ALC-0315脂质配制的RNA-LNPs效力最强（所有p值<0.01）且免疫原性最强（所有p值<0.05），而用SM-102或ALC-0315配制的DNA-LNPs信号持续时间最长。此外，发现所有LNP制剂在肝脏中诱导的表达与注射部位的信号成比例（SM102：r = 0.8787，p<0.0001；ALC0315：r = 0.9012，p<0.00）。总体而言，本研究为主要LNP制剂之间的差异及其在基于DNA和RNA的疫苗接种中的适用性提供了重要见解。
