دورية أكاديمية
أعرض في EDS

Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria.

التفاصيل البيبلوغرافية
العنوان: Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria.
المؤلفون: Meulewaeter S; Ghent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium., Aernout I; Ghent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium., Deprez J; Inflammation Research Center, VIB-UGent, Zwijnaarde, Belgium., Engelen Y; Ghent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium., De Velder M; Ghent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium., Franceschini L; Translational Oncology Research Center, Laboratory for Molecular and Cellular Therapy, Vrije Universiteit Brussel, Brussels, Belgium., Breckpot K; Translational Oncology Research Center, Laboratory for Molecular and Cellular Therapy, Vrije Universiteit Brussel, Brussels, Belgium., Van Calenbergh S; Laboratory of Medicinal Chemistry, Faculty of Pharmacy, Ghent University, Ghent, Belgium., Asselman C; VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Boucher K; VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; VIB Proteomics Core, VIB, Ghent, Belgium., Impens F; VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; VIB Proteomics Core, VIB, Ghent, Belgium., De Smedt SC; Ghent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium., Verbeke R; Ghent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium. Electronic address: Rein.Verbeke@ugent.be., Lentacker I; Ghent Research Group on Nanomedicines, Faculty of Pharmacy, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium. Electronic address: Ine.Lentacker@ugent.be.
المصدر: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Jun; Vol. 370, pp. 379-391. Date of Electronic Publication: 2024 May 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
مواضيع طبية MeSH: Galactosylceramides*/administration & dosage , Galactosylceramides*/chemistry , Mice, Inbred C57BL* , Cancer Vaccines*/administration & dosage , Cancer Vaccines*/immunology , Nanoparticles*/chemistry , Nanoparticles*/administration & dosage , Ovalbumin*/immunology , Ovalbumin*/administration & dosage, Animals ; Female ; mRNA Vaccines ; Adjuvants, Immunologic/administration & dosage ; CD8-Positive T-Lymphocytes/immunology ; RNA, Messenger/administration & dosage ; Mice ; Bacterial Vaccines/administration & dosage ; Bacterial Vaccines/immunology ; Neoplasms/immunology ; Neoplasms/therapy ; Lipids/chemistry ; Liposomes
مستخلص: 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 (iNKT) 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.
Competing Interests: Declaration of competing interest R.V., I.L. and S.D.S. are contributors to patent applications no. WO2020058239A1; Therapeutic nanoparticles and methods of use thereof. and no. WO2023209103; Prevention and treatment of infections with intracellular bacteria., together with I.A.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Cancer; Intracellular bacteria; Lipid nanoparticle; Lipoplex; Modified nucleotides; NKT cell; Route of administration; mRNA vaccine; α-Galactosylceramide
المشرفين على المادة: 0 (Galactosylceramides)
0 (alpha-galactosylceramide)
0 (Cancer Vaccines)
9006-59-1 (Ovalbumin)
0 (mRNA Vaccines)
0 (Adjuvants, Immunologic)
0 (RNA, Messenger)
0 (Bacterial Vaccines)
0 (Lipids)
0 (Lipid Nanoparticles)
0 (Liposomes)
تواريخ الأحداث: Date Created: 20240502 Date Completed: 20240609 Latest Revision: 20240611
رمز التحديث: 20240612
DOI: 10.1016/j.jconrel.2024.04.052
PMID: 38697317
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-4995
DOI:10.1016/j.jconrel.2024.04.052