Vadovics, Máté and Zhao, Wenchen and Daley, Emily F. and Lam, Kieu and Daly, Owen and Rashid, Khalid and Lee, Hailey R. and Schreiner, Petra and Lundgreen, Kendall A. and Gaudette, Brian T. and Shuvaev, Vladimir V. and Arguiri, Evguenia and Muramatsu, Hiromi and Sarkozy, Andras and Mdluli, Thandiswa and Xu, Junchao and Han, Xuexiang and De, Luna Nina and Castano, Diana and Bettini, Emily and Ábrahám, Edit and Lipinszki, Zoltán and Carlucci, Giuseppe and Bansode, Avinash Haridas and Nguyen, Katelyn and Le, Thuc M. and Luu, Tony and Muzykantov, Vladimir R. and Bates, Paul and Allman, David and Mitchell, Michael J. and Locci, Michela and Radu, Caius G. and Heyes, James and Pardi, Norbert (2025) Tailoring the adjuvanticity of lipid nanoparticles by PEG lipid ratio and phospholipid modifications. NATURE NANOTECHNOLOGY, 20. pp. 1312-1322. ISSN 1748-3387
![[img]](https://real.mtak.hu/style/images/fileicons/text.png) |
Text
VadovicsM.pdf - Published Version Restricted to Registered users only Download (6MB) | Request a copy |
Abstract
Lipid nanoparticles (LNPs) represent the leading delivery platform for mRNA vaccines with advantageous biocompatibility, scalability, adjuvant activity and often an acceptable safety profile. Here we investigate the physicochemical characteristics and adjuvanticity of four-component LNPs. Previous vaccine studies have demonstrated that altering the ionizable lipid influences the adjuvanticity of an LNP; however, the impact of the polyethylene glycol lipid and phospholipid has received less attention. Our mRNA-LNP vaccine formulations utilized different phospholipids and varying ratios of polyethylene glycol lipid, whereas the ionizable lipid and cholesterol remained approximately constant. We demonstrate that such modifications impact the magnitude and quality of the vaccine-elicited immune responses. We also dissect the underlying mechanisms and show that the biodistribution and cellular uptake of LNPs correlate with the magnitude and quality of the immune responses. These findings support the rational design of novel LNPs to tailor immune responses (cellular or humoral focused) based on the vaccine application.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Agency and Grant Number: Abramson Cancer Center NCI Grant [P30 016520]; National Institute of Allergy and Infectious Diseases (NIAID) [R01AI146101, R01AI153064, P01AI158571, U19AI181968]; National Laboratory for Biotechnology [2022-2.1.1-NL-2022-00008]; Hungarian Academy of Sciences [LP2017-7/2017, R01AI 152236]; NIH-NCI National Cancer Institute [R01CA283736]; Parker Institute for Cancer Immunotherapy [20221408]; University of California, Los Angeles, Immunology Advisory Committee (IAC) Award; NIH [P30 AI045008, P30 CA016520, SCR_022380] Funding text: We thank the Cell & Developmental Biology Microscopy Core at the University of Pennsylvania. Additionally, the flow cytometry data were generated in the Penn Cytomics and Cell Sorting Shared Resource Laboratory at the University of Pennsylvania and is partially supported by a Abramson Cancer Center NCI Grant (P30 016520). The research identifier number is RRid:SCR_022376. The Pardi laboratory was supported by the National Institute of Allergy and Infectious Diseases (NIAID; R01AI146101, R01AI153064, P01AI158571 and U19AI181968). Z.L. was supported by the National Laboratory for Biotechnology (2022-2.1.1-NL-2022-00008) and the Hungarian Academy of Sciences (Lenduelet Program Grant (LP2017-7/2017)). K.A.L. and P.B. were supported by R01AI 152236. C.G.R. was supported by the NIH-NCI National Cancer Institute; R01CA283736 (C.G.R. and N.P.), the Parker Institute for Cancer Immunotherapy, 20221408 (C.G.R. and N.P.), and the University of California, Los Angeles, Immunology Advisory Committee (IAC) Award (C.G.R.). We also thank Y. Du, H. Sun and E. L. Prak of the Human Immunology Core (HIC) at the Perelman School of Medicine at the University of Pennsylvania for assistance with the Luminex assays, and M. Eldabbas, E. Maddox, T. Sinha and J. Shu for the preparation of deidentified primary human monocytes. The HIC is supported in part by NIH P30 AI045008 and P30 CA016520. HIC RRID: SCR_022380. We also thank M. Katona at the University of Pittsburgh for guidance in confocal imaging quantification methods; L. Palmer, H. Mahmoud, A. Martin, A. Liu and K. McClintock for their contributions and support throughout this project; and the Proteomics Research Group of the HUN-REN BRC Core Facility for performing the liquid chromatography/mass spectrometry analysis and validation of recombinant proteins. |
| Uncontrolled Keywords: | EXPRESSION; DELIVERY; MESSENGER-RNA; SYSTEMS; KINETICS; VACCINES; IMPACT; Nanoscience & Nanotechnology; |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 19 Mar 2026 08:53 |
| Last Modified: | 19 Mar 2026 08:53 |
| URI: | https://real.mtak.hu/id/eprint/235898 |
Actions (login required)
 |
Edit Item |
