A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis
Abstract
Precision therapy for immune tolerance: Autoimmune diseases, such as multiple sclerosis (MS), result from a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes. Current treatments can cause systemic immune suppression and side effects such as increased risk of infections. Krienke et al. designed a messenger RNA vaccine strategy that lacks adjuvant activity and delivers MS autoantigens into lymphoid dendritic cells. This approach expands a distinct type of antigen-specific effector regulatory T cell that suppresses autoreactivity against targeted autoantigens and promotes bystander suppression of autoreactive T cells against other myelin-specific autoantigens. In mouse models of MS, the vaccine delayed the onset and reduced the severity of established disease without showing overt symptoms of general immune suppression. Science , this issue p. 145
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Organ selectivity can be achieved by adjusting the proportions of lipid components.
“Organ selectivity can also be achieved by adjusting the proportions of lipid components, for example, to design spleen-targeted mRNA vaccines26,27 or lung-targeted genome editing delivery systems114,134.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [27]
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“Negatively charged cLNPs targeting the spleen were used to create a non-inflammatory modified mRNA vaccine to treat autoimmune encephalomyelitis using a low N:P ratio (102).”
Method
- Authors
- Krienke, C., Kolb, L., Diken, E., Streuber, M., Kirchhoff, S., Bukur, T., Akilli-Öztürk, Ö., Kranz, L. M., Berger, H., Petschenka, J., Diken, M., Kreiter, S., Yogev, N., Waisman, A., Karikó, K., Türeci, Ö., & Sahin, U.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- TRON – Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz 55131, Germany.
- BioNTech (Germany) (DE)
- Boehringer Ingelheim (Germany) (DE)
- Corresponding author
- Kolb, Laura
- Diken, Elif
- ORCID
- Venue
- Science
- Published
- 2021-01-08
- Volume
- 371
- Issue
- 6525
- Pages
- 145-153
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W3120567430
- Cited by
- 520
- References
- 53
- Citations by year
- 2026: 89 · 2025: 89 · 2024: 98 · 2023: 87 · 2022: 84 · 2021: 72
- FWCI
- 56.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft DFG (SFB/CRC-TR 128)
- Immunology Research Center (FZI) Mainz (FZI-TRP 2014-12)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- mRNA vaccines, experimental autoimmune encephalomyelitis, multiple sclerosis, regulatory T cells, dendritic cells, myelin autoantigens, bystander suppression, immune tolerance, adjuvant-free vaccine, autoreactive T cells
- MeSH terms
- mRNA Vaccines, Animals, Antigen-Presenting Cells, Autoantigens, Encephalomyelitis, Autoimmune, Experimental, Immunosuppression Therapy, Inflammation, Mice, Inbred C57BL, Multiple Sclerosis, Pseudouridine, RNA, Messenger, Vaccines, Synthetic, Bystander Effect, T-Lymphocytes, Regulatory, Mice
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