MOG-AMP-B microparticles loaded with myelin antigen reverse experimental autoimmune encephalomyelitis by promoting tolerogenic B cell presentation

Multiple Sclerosis (MS) affects nearly 1 million people in the US, characterized by immune-mediated demyelination and neurodegeneration. Current therapies broadly suppress the immune system, leading to systemic immunosuppression and increased risk of infection, without offering a cure. A critical gap exists for antigen-specific therapies that could selectively target autoreactive cells while preserving protective immunity. B cell dysregulation is a significant driver of MS pathology, yet antigen-specific tolerance strategies have largely overlooked B cells as a primary target.

Researchers developed MOG35-55 peptide-loaded acetalated dextran microparticles (AMPs) designed to associate with B cells, forming MOG-AMP-B. These particles were first shown to enhance IL-10 secretion and MHCII expression in B cells in vitro, promoting tolerogenic antigen presentation. The therapeutic efficacy of MOG-AMP-B was then evaluated in a late therapeutic mouse model of experimental autoimmune encephalomyelitis (EAE). The study assessed primary endpoints including central nervous system (CNS) inflammation, activation status of dendritic cells and macrophages, and the populations of regulatory T- and B cells.

Antigen-loaded acetalated dextran microparticles (AMP) were found to surface-associate with B cells, significantly enhancing IL-10 secretion and MHCII expression, thereby promoting a tolerogenic antigen presentation phenotype. When administered in a late therapeutic model of experimental autoimmune encephalomyelitis (EAE), MOG-AMP-Bs induced a profound therapeutic effect. The treatment led to a remarkable recovery from the disease. > MOG-AMP-Bs resulted in unprecedented recovery, reducing central nervous system (CNS) inflammation, downregulating activated dendritic cells and macrophages, and increasing regulatory T- and B cells. Crucially, MOG-AMP-Bs did not reduce the ability of animals to respond to a viral infection, indicating a highly specific immune modulation without broad immunosuppression.