Oxidized mannan-MOG35-55 conjugate as a platform for antigen-specific immune modulation in multiple sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by autoreactive T-cell responses against myelin antigens. Current disease-modifying therapies (DMTs) broadly suppress immune activity but do not restore antigen-specific immune tolerance and may cause significant adverse effects. Antigen-specific immunotherapies offer a rational alternative aimed at selectively re-educating the immune system without compromising protective immunity. Structural determinants of myelin antigens, including arginine-dependent conformational stability and post-translational modifications such as citrullination, critically influence their immunogenic and tolerogenic properties. Recent advances highlight the potential of oxidized mannan-conjugated myelin oligodendrocyte glycoprotein peptide (OM-MOG35-55) to modulate antigen-specific immune responses in experimental models and human immune cells. Studies suggest that OM-MOG35-55 can influence dendritic cell (DC)-mediated antigen presentation and favor the expansion of CD4+PD-1+ and CD4+CD25+Foxp3+ T-cell populations and the production of regulatory cytokines such as IL-10 and TGF-β1. When combined with vitamin D3 conditioning of DCs, the immunomodulatory potential of OM-MOG35-55 appears enhanced. Nevertheless, the precise mechanisms underlying OM-MOG-mediated immune modulation are not fully defined, and the antigenic heterogeneity of MS and the limited predictive value of EAE models highlight the need for cautious interpretation of preclinical findings. This mini-review integrates structural, immunological, and translational evidence supporting OM-MOG35-55 as a promising platform for antigen-specific immunotherapeutic design and proposes a roadmap toward clinical validation of this immunotherapeutic strategy for MS.