Therapeutic DNA vaccination as a repair strategy following spinal cord injury.
Myelin-derived proteins, such as tenascin-R (TN-R), myelin associate glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and Nogo-A, inhibit the central nervous system regeneration. In this study, the DNA vaccine encoding for oligodendrocyte and myelin-related antigens was employed to attenuate the axonal growth inhibitory properties of myelin in the setting of spinal cord injury. Using a rat spinal cord dorsal hemisection model, the vaccine directed against the inhibitory epitopes of Nogo-A, MAG, OMgp, and TN-R was administered intramuscularly once a week following spinal cord injury, supplemented with local application of specific anti-sera against the four antigens. Anterograde labeling of dorsal column fibers showed active axonal regeneration through the lesion site at the eighth week following the treatment in experimental group but not in control groups. Light microscopic and ultrastructural analysis revealed that vaccination with these myelin-related antigens did not lead to demyelinating disease. OMgp and TN-R levels were down-regulated at the lesion site together with a parallel increase in growth-associated protein 43 levels in the treatment groups. This study reveals the effective approach of a DNA vaccine strategy by attaining the special antibody to direct neutralization of the myelin inhibitors during spinal cord injury.
Kou
Sheng-Bin
SB
Neurosurgery Institute of Guangdong, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, 253# Gongye Road, 510282, Guangzhou, People's Republic of China.
Xu
Gang
G
Jiang
Xiao-Dan
XD
Xu
Ru-Xiang
RX
Tang
Yan-Ping
YP
Xu
Gang
G
Cai
Ying-Qian
YQ
Du
Mou-Xuan
MX
Xiao
Zhi-Cheng
ZC
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology; D000939:Epitopes / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D007116:Immunization, Passive; D009043:Motor Activity; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration; D000070798:Nogo Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D019063:Tenascin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000627:therapeutic use*
D000939:Epitopes; D058851:GPI-Linked Proteins; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000070798:Nogo Proteins; C560532:Omg protein, rat; C000603197:Rtn4 protein, rat; D019063:Tenascin; D019444:Vaccines, DNA; C074638:tenascin R