Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease

Spinal cord injury results in a massive loss of neurons, and thus of functi on. We recently reported that passive transfer of autoimmune T cells direct ed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passiv e transfer of T cells was found to be at least 1 week. Here we show that po sttraumatic T cell-based active vaccination is also neuroprotective. Immuni zation with myelin-associated antigens such as myelin basic protein (MBP) s ignificantly promoted recovery after spinal cord contusion injury in the ra t model. To reduce the risk of autoimmune disease while retaining the benef it of the immunization, we vaccinated the rats immediately after severe inc omplete spinal cord injury with MBP-derived altered peptide ligands. Immuni zation with these peptides resulted in significant protection from neuronal loss and thus in a reduced extent of paralysis, assessed by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts and magnetic resonance imaging supported the behavioral results. Further optimization o f nonpathogenic myelin-derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strat egy for the prevention of total paralysis after incomplete spinal cord inju ry.