A novel non-galactosylated tolerogenic antigen-specific vaccine protects against arthritis via VISTA-expressing regulatory T cells in DRB1*04:01 mice

ABSTRACT: 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 incurable. Advancements in peptide-based vaccination may open new avenues for treating autoimmune diseases by inducing immune tolerance while maintaining normal immune function. We have demonstrated a potential vaccine against RA, made by mouse major histocompatibility complex class II (Aq) protein bounding 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 and simplify this vaccine, we modified the amino acid residue at position 265 and conjugated it with the human DRB1*04:01 molecule. Remarkably, this modified vaccine proved effective in DRB1*04:01-expressing mice without the need for galactosylation at position 264. The vaccine exerts its protective effect through the activation and expansion of VISTA-positive nonconventional regulatory T cells, leading to a potent dominant suppressive response that prevents arthritis development in mice. The new modified vaccine for RA, offers a novel therapeutic approach with potential clinical implications for human autoimmune diseases.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): B-lymphocyte, T-lymphocyte

SUBMITTER: Christian Beusch  

LAB HEAD: Rikard Holmdahl

PROVIDER: PXD056818 | Pride | 2026-06-29

REPOSITORIES: Pride