Recombinant DNA vaccine encoding multiple domains related to inhibition of neurite outgrowth: a potential strategy for axonal regeneration.
Myelin-derived proteins, such as tenascin-R (TN-R), myelin associate glycoprotein (MAG), and Nogo-A, inhibit the CNS regeneration. By targeting specifically the inhibitory epitopes, we have investigated whether vaccination with a recombinant DNA molecule encoding multiple domains of myelin inhibitors may be useful in CNS repair. We show here that the recombinant DNA vaccine is able to activate the immune system but does not induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Importantly, it promotes axonal regeneration in a spinal cord injury model. Thus, the application of DNA vaccine, encoding multiple specific domains of major inhibitory proteins and/or their receptors, provides another promising approach to overcome the inhibitory barriers during CNS regeneration.
Xu
Gang
G
Department of Clinical Research, Singapore General Hospital, Singapore.
Nie
Du-Yu
DY
Chen
Ju-Tao
JT
Wang
Chao-Yang
CY
Yu
Feng-Gang
FG
Sun
Li
L
Luo
Xue-Gang
XG
Ahmed
Sohail
S
David
Samuel
S
Xiao
Zhi-Cheng
ZC
D000818:Animals; D001369:Axons / Q000276:immunology / Q000502:physiology*; D019556:COS Cells; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000276:immunology; D009416:Nerve Regeneration / Q000276:immunology*; D016501:Neurites / Q000276:immunology / Q000502:physiology*; D000070798:Nogo Proteins; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000276:immunology / Q000628:therapy*; D019063:Tenascin / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000627:therapeutic use*
D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat; D019063:Tenascin; D019444:Vaccines, DNA; C074638:tenascin R