A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis

The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic de...

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Veröffentlicht in:Science (American Association for the Advancement of Science) Jg. 371; H. 6525; S. 145
Hauptverfasser: Krienke, Christina, Kolb, Laura, Diken, Elif, Streuber, Michael, Kirchhoff, Sarah, Bukur, Thomas, Akilli-Öztürk, Özlem, Kranz, Lena M, Berger, Hendrik, Petschenka, Jutta, Diken, Mustafa, Kreiter, Sebastian, Yogev, Nir, Waisman, Ari, Karikó, Katalin, Türeci, Özlem, Sahin, Ugur
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 08.01.2021
Schlagworte:
Animals
Antigen-Presenting Cells
Autoantigens - genetics
Bystander Effect - immunology
Encephalomyelitis, Autoimmune, Experimental - therapy
Immunosuppression Therapy - methods
Inflammation - immunology
Mice
Mice, Inbred C57BL
mRNA Vaccines
Multiple Sclerosis - therapy
Pseudouridine - analogs & derivatives
Pseudouridine - chemistry
RNA, Messenger - adverse effects
RNA, Messenger - chemistry
RNA, Messenger - genetics
T-Lymphocytes, Regulatory - immunology
Vaccines, Synthetic - adverse effects
Vaccines, Synthetic - therapeutic use
ISSN:1095-9203, 1095-9203
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Zusammenfassung:The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1Ψ mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c antigen-presenting cells in the absence of costimulatory signals. In several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1Ψ mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (T cell) populations. Notably, these T cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1095-9203
1095-9203
DOI:10.1126/science.aay3638