Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria
- Author
- Sofie Meulewaeter (UGent) , Ilke Aernout (UGent) , Joke Deprez (UGent) , Yanou Engelen (UGent) , Margo De Velder (UGent) , Lorenzo Franceschini, Karine Breckpot, Serge Van Calenbergh (UGent) , Caroline Asselman (UGent) , Katie Boucher (UGent) , Francis Impens (UGent) , Stefaan De Smedt (UGent) , Rein Verbeke (UGent) and Ine Lentacker (UGent)
- Organization
- Project
-
- Understanding and modulating the pro-inflammatory activity of lipid nanoparticles (LNP) in the COVID-19 mRNA vaccines: towards the development of more effective LNP formulations.
- Exploration of an mRNA based nanovaccine platform and immunopeptidomics for the development of more effective tuberculosis vaccines.
- Exploring and advancing mRNA lipid nanoparticles for the in situ generation of CAR-Ms
- Immunopeptidomics-based Development of Next-Generation Bacterial mRNA Vaccines
- Vaccination with nucleoside-modified mRNA-ceramide lipoplexes: a phase I trial in stage IV lung carcinoma patients
- Further development of mRNA Galsomes as nanovaccines for cancer immunotherapy: combination with checkpoint inhibition and translation to the clinic.
- Proteomics-derived epitopes for dramatically improved anticancer and antibacterial vaccine development
- LNP-DECODE: Deciphering the adjuvants activity of lipid nanoparticle-based mRNA vaccines in primary dendritic cells
- Vaccine-induced and ISG15-mediated immune responses to Bacterial Infection and Moyamoya Disease
- Accellerating towards clinical validation of Galsome nanovaccines
- Alliantieonderzoeksgroep: Kankerimmunotherapie middels geavanceerde ‘verpakkingsmaterialen’ van mRNA therapeutica
- Smart design nanoParticles to Activate immune Responses against Cancer (SPARC)
- Abstract
- Although various types of mRNA-based vaccines have been explored, the optimal conditions for induction of both humoral and cellular immunity remain rather unknown. In this study, mRNA vaccines of nucleoside-modified mRNA in lipoplexes (LPXs) or lipid nanoparticles (LNPs) were evaluated after administration in mice through different routes, assessing mRNA delivery, tolerability and immunogenicity. In addition, we investigated whether mRNA vaccines could benefit from the inclusion of the adjuvant alpha-galactosylceramide (αGC), an invariant Natural Killer T (NKT) cell ligand. Intramuscular (IM) vaccination with ovalbumin (OVA)-encoding mRNA encapsulated in LNPs adjuvanted with αGC showed the highest antibody- and CD8+ T cell responses. Furthermore, we observed that addition of signal peptides and endocytic sorting signals of either LAMP1 or HLA-B7 in the OVA-encoding mRNA sequence further enhanced CD8+ T cell activation although reducing the induction of IgG antibody responses. Moreover, mRNA LNPs with the ionizable lipidoid C12-200 exhibited higher pro-inflammatory- and reactogenic activity compared to mRNA LNPs with SM-102, correlating with increased T cell activation and antitumor potential. We also observed that αGC could further enhance the cellular immunity of clinically relevant mRNA LNP vaccines, thereby promoting therapeutic antitumor potential. Finally, a Listeria monocytogenes mRNA LNP vaccine supplemented with αGC showed synergistic protective effects against listeriosis, highlighting a key advantage of co-activating iNKT cells in antibacterial mRNA vaccines. Taken together, our study offers multiple insights for optimizing the design of mRNA vaccines for disease applications, such as cancer and intracellular bacterial infections.
- Keywords
- Lipid nanoparticle, Lipoplex, mRNA vaccine, NKT cell, alpha-Galactosylceramide, Modified nucleotides, Cancer, Intracellular bacteria, Route of administration, KILLER T-CELLS, LISTERIA-MONOCYTOGENES, DENDRITIC CELLS, NKT CELLS, SUPPRESSOR-CELLS, IMMUNE-RESPONSES, CLASS-I, INNATE, DELIVERY
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HWQ101XEFTD4H76FNX2KSK1J
- MLA
- Meulewaeter, Sofie, et al. “Alpha-Galactosylceramide Improves the Potency of MRNA LNP Vaccines against Cancer and Intracellular Bacteria.” JOURNAL OF CONTROLLED RELEASE, vol. 370, 2024, pp. 379–91, doi:10.1016/j.jconrel.2024.04.052.
- APA
- Meulewaeter, S., Aernout, I., Deprez, J., Engelen, Y., De Velder, M., Franceschini, L., … Lentacker, I. (2024). Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria. JOURNAL OF CONTROLLED RELEASE, 370, 379–391. https://doi.org/10.1016/j.jconrel.2024.04.052
- Chicago author-date
- Meulewaeter, Sofie, Ilke Aernout, Joke Deprez, Yanou Engelen, Margo De Velder, Lorenzo Franceschini, Karine Breckpot, et al. 2024. “Alpha-Galactosylceramide Improves the Potency of MRNA LNP Vaccines against Cancer and Intracellular Bacteria.” JOURNAL OF CONTROLLED RELEASE 370: 379–91. https://doi.org/10.1016/j.jconrel.2024.04.052.
- Chicago author-date (all authors)
- Meulewaeter, Sofie, Ilke Aernout, Joke Deprez, Yanou Engelen, Margo De Velder, Lorenzo Franceschini, Karine Breckpot, Serge Van Calenbergh, Caroline Asselman, Katie Boucher, Francis Impens, Stefaan De Smedt, Rein Verbeke, and Ine Lentacker. 2024. “Alpha-Galactosylceramide Improves the Potency of MRNA LNP Vaccines against Cancer and Intracellular Bacteria.” JOURNAL OF CONTROLLED RELEASE 370: 379–391. doi:10.1016/j.jconrel.2024.04.052.
- Vancouver
- 1.Meulewaeter S, Aernout I, Deprez J, Engelen Y, De Velder M, Franceschini L, et al. Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria. JOURNAL OF CONTROLLED RELEASE. 2024;370:379–91.
- IEEE
- [1]S. Meulewaeter et al., “Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria,” JOURNAL OF CONTROLLED RELEASE, vol. 370, pp. 379–391, 2024.
@article{01HWQ101XEFTD4H76FNX2KSK1J,
abstract = {{Although various types of mRNA-based vaccines have been explored, the optimal conditions for induction of both humoral and cellular immunity remain rather unknown. In this study, mRNA vaccines of nucleoside-modified mRNA in lipoplexes (LPXs) or lipid nanoparticles (LNPs) were evaluated after administration in mice through different routes, assessing mRNA delivery, tolerability and immunogenicity. In addition, we investigated whether mRNA vaccines could benefit from the inclusion of the adjuvant alpha-galactosylceramide (αGC), an invariant Natural Killer T (NKT) cell ligand. Intramuscular (IM) vaccination with ovalbumin (OVA)-encoding mRNA encapsulated in LNPs adjuvanted with αGC showed the highest antibody- and CD8+ T cell responses. Furthermore, we observed that addition of signal peptides and endocytic sorting signals of either LAMP1 or HLA-B7 in the OVA-encoding mRNA sequence further enhanced CD8+ T cell activation although reducing the induction of IgG antibody responses. Moreover, mRNA LNPs with the ionizable lipidoid C12-200 exhibited higher pro-inflammatory- and reactogenic activity compared to mRNA LNPs with SM-102, correlating with increased T cell activation and antitumor potential. We also observed that αGC could further enhance the cellular immunity of clinically relevant mRNA LNP vaccines, thereby promoting therapeutic antitumor potential. Finally, a Listeria monocytogenes mRNA LNP vaccine supplemented with αGC showed synergistic protective effects against listeriosis, highlighting a key advantage of co-activating iNKT cells in antibacterial mRNA vaccines. Taken together, our study offers multiple insights for optimizing the design of mRNA vaccines for disease applications, such as cancer and intracellular bacterial infections.}},
author = {{Meulewaeter, Sofie and Aernout, Ilke and Deprez, Joke and Engelen, Yanou and De Velder, Margo and Franceschini, Lorenzo and Breckpot, Karine and Van Calenbergh, Serge and Asselman, Caroline and Boucher, Katie and Impens, Francis and De Smedt, Stefaan and Verbeke, Rein and Lentacker, Ine}},
issn = {{0168-3659}},
journal = {{JOURNAL OF CONTROLLED RELEASE}},
keywords = {{Lipid nanoparticle,Lipoplex,mRNA vaccine,NKT cell,alpha-Galactosylceramide,Modified nucleotides,Cancer,Intracellular bacteria,Route of administration,KILLER T-CELLS,LISTERIA-MONOCYTOGENES,DENDRITIC CELLS,NKT CELLS,SUPPRESSOR-CELLS,IMMUNE-RESPONSES,CLASS-I,INNATE,DELIVERY}},
language = {{eng}},
pages = {{379--391}},
title = {{Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria}},
url = {{http://doi.org/10.1016/j.jconrel.2024.04.052}},
volume = {{370}},
year = {{2024}},
}
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