Open this publication in new window or tab >>Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; School of Medicine, Shanghai University, Shanghai, China.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Medical Inflammation Research, MediCity Research Laboratory, University of Turku, Turku, Finland.
Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Department of Pharmacological & Technological Chemistry, I. M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.
Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, & Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, Frankfurt am Main, Germany; Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Medical Inflammation Research, MediCity Research Laboratory, University of Turku, Turku, Finland.
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2025 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024Article in journal (Refereed) Epub ahead of print
Abstract [en]
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, cartilage damage, and bone erosion. Despite improvements with the introduction of biological disease-modifying anti-rheumatic drugs (DMARDs), RA remains an incurable life-long disease. Advancements in peptide-based vaccination may open new avenues for treating autoimmune diseases, including RA, by inducing immune tolerance while maintaining normal immune function. We have already demonstrated the efficacy of a potent vaccine against RA, consisting of the mouse major histocompatibility complex class II (Aq) protein bound to the immunodominant type II collagen peptide COL2259-273, which needed to be galactosylated at position 264. To translate the vaccine to humans and to further enhance vaccine efficacy, we modified the glycine residue at position 265 and conjugated it with the human DRB1∗04:01 molecule. Remarkably, this modified vaccine (named DR4-AL179) provided robust effectiveness in suppressing arthritis in DRB1∗04:01-expressing mice without the need for galactosylation at position 264. DR4-AL179 vaccination induces tolerance involving multiple immunoregulatory pathways, including the activation of V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA)-positive nonconventional regulatory T cells, which contribute to a potent suppressive response preventing arthritis development in mice. This modified RA vaccine offers a novel therapeutic potential for human autoimmune diseases.
Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
COL2, immune checkpoints, MHCII, regulatory T cells, rheumatoid arthritis, T cell tolerance, tolerogenic, vaccine, VISTA
National Category
Immunology in the Medical Area Rheumatology Autoimmunity and Inflammation
Identifiers
urn:nbn:se:umu:diva-238834 (URN)10.1016/j.ymthe.2025.04.034 (DOI)40285352 (PubMedID)2-s2.0-105004434061 (Scopus ID)
Funder
Swedish Research Council, 2024-02575Novo Nordisk FoundationKnut and Alice Wallenberg Foundation, 2019.0059Lars Hierta Memorial FoundationSwedish Rheumatism AssociationKing Gustaf V Jubilee Fund, SGI-2023-0993
2025-06-042025-06-042025-06-04