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 function. We recently reported that passive transfer of autoimmune T cells directed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passive transfer of T cells was found to be at least 1 week. Here we show that posttraumatic T cell-based active vaccination is also neuroprotective. Immunization with myelin-associated antigens such as myelin basic protein (MBP) significantly promoted recovery after spinal cord contusion injury in the rat model. To reduce the risk of autoimmune disease while retaining the benefit of the immunization, we vaccinated the rats immediately after severe incomplete spinal cord injury with MBP-derived altered peptide ligands. Immunization 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 of nonpathogenic myelin-derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strategy for the prevention of total paralysis after incomplete spinal cord injury.
Hauben
E
E
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Agranov
E
E
Gothilf
A
A
Nevo
U
U
Cohen
A
A
Smirnov
I
I
Steinman
L
L
Schwartz
M
M
D000276:Adjuvants, Immunologic; D019943:Amino Acid Substitution; D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000209:etiology / Q000517:prevention & control*; D003288:Contusions; D002818:Cordotomy; D005106:Exploratory Behavior; D005260:Female; D006168:Guinea Pigs; D016233:Immunotherapy, Active; D008124:Locomotion; D008279:Magnetic Resonance Imaging; D008297:Male; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D010264:Paraplegia / Q000209:etiology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012449:Safety; D016037:Single-Blind Method; D013119:Spinal Cord Injuries / Q000150:complications / Q000276:immunology / Q000628:therapy*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D001324:Autoantigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C115314:myelin basic protein 87-99