LNP-mRNA vaccine prevents type 1 diabetes in non-obese diabetes mice.

Autor: Chen J; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China., Hu Y; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China., Chen Y; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China., Zhou Z; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China., Shen Y; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China., Wang Y; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China., Liu Z; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China., Li X; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China., Su Z; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: zhiguisu707@cpu.edu.cn., Wu J; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: wujie@cpu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Nov; Vol. 375, pp. 513-523. Date of Electronic Publication: 2024 Sep 20.
DOI: 10.1016/j.jconrel.2024.09.020
Abstrakt: Islet-antigen-specific tolerization is a key goal of experimental immunotherapies for type 1 diabetes. mRNA-based vaccines have demonstrated the feasibility of RNA delivery in inducing antigen tolerance in autoimmune diseases. In this study, mRNA vaccine, encoded tandem glutamic acid decarboxylase 65 (GAD65) epitopes and cholera toxin B subunit (CTB-GADIII), prepared by an in vitro transcription (IVT) system and encapsulated with lipid nanoparticles (LNP), was intramuscularly administered to non-obese diabetic (NOD) and cyclophosphamide (Cy)-NOD mice respectively. The results showed that the mRNA vaccines significantly reduced the incidence rate of type 1 diabetes, delayed the disease progression, improved glucose tolerance, and protected pancreatic morphology and function compared with the controls. Meanwhile, the vaccines also reduced the levels of autoantibodies to glutamic acid decarboxylase (GADA) and insulin (IAA) in the serum. Furthermore, the proportion of CD4 + T helper cell subsets was modulated in the spleen of mice treated with mRNA vaccines, in correspondence with the increased levels of IL-10 and TGF-β in serum, suggesting the possible mechanism of immune tolerance. This study provides experimental evidence for the application of mRNA vaccines encoding self-antigens in the prevention or treatment of type 1 diabetes.
Competing Interests: Declaration of competing interest All authors declared that there is no conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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