Autoantigen-loaded Polymeric Microparticles associate with B cells and promote tolerogenic antigen presentation in a mouse model of experimental autoimmune encephalomyelitis

Almost 1 million people in the United States suffer from multiple sclerosis (MS). Current therapies suppress protective immunity and are non-curative. Antigen-specific therapies can selectively suppress autoreactive cells, preserving protective immunity. B cell dysregulation, a major driver of MS, remains largely untargeted for antigen-specific tolerance. We hypothesize that targeting B cells with antigen-loaded microparticles will enhance therapeutic efficacy. Here, we demonstrate that antigen-loaded acetalated dextran microparticles (AMP) surface-associate with B cells and enhance IL-10 secretion and MHCII expression, promoting tolerogenic antigen presentation. Leveraging this property, we developed a therapy using myelin oligodendrocyte (MOG35-55) peptide-loaded AMPs associated with B cells (MOG-AMP-B). Administering MOG-AMP-Bs in a late therapeutic model of multiple sclerosis resulted in unprecedented recovery, reducing central nervous system (CNS) inflammation, downregulating activated dendritic cells and macrophages, and increasing regulatory T- and B cells. MOG-AMP-Bs did not reduce the ability of animals to respond to a viral infection, representing a highly effective antigen-specific therapy for restoring immune balance in autoimmunity. B-cell dysregulation is a key feature of autoimmunity, and strategies to target pathogenic B cells are highly desirable. Here, the authors show that autoantigen-loaded acetalated dextran microparticles associate with the surface of B cells in vivo and induce regulatory B cells, achieving antigen-specific tolerance and promising therapeutic efficacy in a mouse model of experimental autoimmune encephalomyelitis.