DNA vaccination efficiently induces antibodies to Nogo-A and does not exacerbate experimental autoimmune encephalomyelitis.
Antibodies against the neurite outgrowth inhibitor Nogo-A enhance axonal regeneration following spinal cord injury. However, antibodies directed against myelin components can also enhance CNS inflammation. The present study was designed to assess the efficacy of DNA vaccination for generating antibodies against Nogo-A and to study their pathogenic potential in a mouse model for multiple sclerosis. Mice were immunized by a single i.m. injection of a plasmid expression vector encoding either full length membrane-integral Nogo-A equipped with a signal peptide or two versions of its large N-terminal extramembrane region. The presence of serum antibodies to Nogo-A was measured 4 weeks after injection by ELISA, Western blotting and immunohistochemistry. DNA vaccination efficiently induced production of Nogo-A-specific antibodies that recognized recombinant, intracellular Nogo-A in cell culture but also stained native Nogo-A on the oligodendrocyte surface. Experimental autoimmune encephalomyelitis was induced in DNA-vaccinated mice by immunization with proteolipid peptide (a.a. 139-154). In contrast to vaccination with DNA encoding myelin oligodendrocyte glycoprotein that exacerbates this disease, Nogo-A DNA vaccination did not enhance clinical severity of disease. In summary, DNA vaccination is a simple and efficient method for generating an antibody response to Nogo-A. No pathogenicity was observed even during a full-blown inflammatory response of the central nervous system.
Bourquin
Carole
C
Department of Neuroimmunology, Max-Planck Institute for Neurobiology, Am Klopferspitz 18a, 82152 Martinsried, Germany. carole.bourquin@med.uni-muenchen.de
van der Haar
Marjan E
ME
Anz
David
D
Sandholzer
Nadja
N
Neumaier
Irmgard
I
Endres
Stefan
S
Skerra
Arne
A
Schwab
Martin E
ME
Linington
Christopher
C
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D015153:Blotting, Western; D016466:CHO Cells; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D006224:Cricetinae; D003412:Cricetulus; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology*; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000187:drug effects; D010957:Plasmids / Q000235:genetics; D051381:Rats; D019444:Vaccines, DNA / Q000494:pharmacology*
D019138:Antibodies, Blocking; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; D019444:Vaccines, DNA