TY - JOUR
T1 - DNA vaccination efficiently induces antibodies to Nogo-A and does not exacerbate experimental autoimmune encephalomyelitis
AU - Bourquin, Carole
AU - van der Haar, Marjan E.
AU - Anz, David
AU - Sandholzer, Nadja
AU - Neumaier, Irmgard
AU - Endres, Stefan
AU - Skerra, Arne
AU - Schwab, Martin E.
AU - Linington, Christopher
N1 - Funding Information:
This study was supported by grants from the Else-Kröner Fresenius Foundation (C.B. and S.E.) and the German Research Foundation (DFG En 169/7-2 and Graduiertenkolleg 1202 to C.B. and S.E., Excellency cluster CiPSM 114 to S.E. and A.S.), from LMUexcellent (research professorship to S.E.) and from the Multiple Sclerosis Society (C.L.).
PY - 2008/6/24
Y1 - 2008/6/24
N2 - 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.
AB - 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.
KW - DNA vaccination
KW - Immunization
KW - Multiple sclerosis
KW - Myelin
KW - Nogo-A
UR - http://www.scopus.com/inward/record.url?scp=44249113802&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2008.04.026
DO - 10.1016/j.ejphar.2008.04.026
M3 - Article
C2 - 18495110
AN - SCOPUS:44249113802
SN - 0014-2999
VL - 588
SP - 99
EP - 105
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -