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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Vydáno v:	Science (American Association for the Advancement of Science) Ročník 371; číslo 6525; s. 145
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 08.01.2021
Témata:	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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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1095-9203 1095-9203
DOI:	10.1126/science.aay3638