Christina Krienke and colleagues have designed an mRNA vaccine that delayed the onset of and reduced the severity of multiple sclerosis-like disease in mice. The vaccine restores the body's tolerance to its own proteins, suppressing the characteristic immune overreactivity of the disease. The vaccine developed by Krienke et al. works in a targeted fashion to promote tolerance to specific disease-related proteins, an improvement over other approaches to treating the disease that induce systemic immune suppression that can leave an individual vulnerable to other infections. The vaccine consists of a lipid nanoparticle packed with modified and purified mRNA that encodes disease-related self-antigens that are normally the triggers for an autoimmune response. In their experiments in mice with autoimmune encephalomyelitis, a mouse model for human multiple sclerosis, the researchers found that the vaccine caused the antigens to be presented on lymphoid dendritic cells without provoking an inflammatory immune response. This new antigen tolerance led to the expansion of regulatory T cells that suppressed the autoimmune response against these types of antigens, and promoted the suppression of other T cells that attack proteins in myelin, the insulating sheath around nerve fibers that is destroyed in multiple sclerosis. The ability to quickly produce mRNA vaccines containing the code for an individual's own antigens may point the way to creating personalized autoimmune disease treatments, the researchers suggest.
