A tolerogenic mRNA-LNP vaccine alleviates neuroinflammation and demyelination in experimental autoimmune encephalomyelitis.

Authors

Yi Song, Zhangchi Dongye, Jiaxi Yao, Xiaonan Zhao, Tao Mo, Shiyu Yang, Cong Sun, Tingting Zhao, Jian Li, Yuzhang Wu

Published in

Science bulletin. Aug 05, 2026. Epub Aug 05, 2026.

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Current non-specific immunosuppressive therapies carry risks of infection and malignancy. Antigen-specific tolerance induction presents a promising alternative. Here, we developed a messenger RNA-lipid nanoparticle (mRNA-LNP) vaccine (LiH-LNPs) encoding a tandem fusion of epitopes from three MS-associated myelin antigens. LiH-LNPs alleviated inflammatory infiltration and demyelination in experimental autoimmune encephalomyelitis (EAE). Single-cell RNA sequencing revealed that LiH-LNPs reshaped the spinal cord microenvironment toward inflammation resolution by reducing the abundance and inflammatory activity of infiltrating myeloid cells and activated microglia, inducing apoptosis of encephalitogenic T cells while increasing regulatory T (Treg) cell abundance and suppressive activity. These findings provide mechanistic insights into antigen-specific immunotherapy for MS and highlight the potential application of mRNA vaccine-based antigen-specific therapy for autoimmune diseases.

PMID:
42613282
Bibliographic data and abstract were imported from PubMed on 19 Aug 2026.

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