|
 |
|||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||
 |
 |
|
|
a Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium b Cellular Genetics Unit, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium c Microbial Pathogenesis Unit, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium d Department of Pathology, Université Catholique de Louvain, Brussels, Belgium e Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium
Key Words: EAE • vaccine • cytokine • autoimmunity • Th17
Address for correspondence: Dr. C. Uyttenhove, Ludwig Institute for Cancer Research, Brussels Branch, 74 av. Hippocrate UCL 7459, B-1200 Brussels, Belgium. Voice: +32-2-764-74-18; fax: +32-2-762-94-05. catherine.uyttenhove{at}bru.licr.org
Excessive or inappropriate production of IL-17A has been reported in diseases such as rheumatoid arthritis, asthma, and multiple sclerosis. The potential clinical relevance of these correlations was suggested by the protective effects of anti-IL-17A monoclonal antibodies in various mouse disease models. However, the chronic nature of the corresponding human afflictions raises great challenges for Ab-based therapies. An alternative to passive Ab therapy is autovaccination. Covalent association of self-cytokines with foreign proteins has been reported to induce the production of antibodies capable of neutralizing the biological activity of the target cytokine. We recently reported that cross-linking of IL-17A to ovalbumin produced highly immunogenic complexes that induced long-lasting IL-17A-neutralizing antibodies. Vaccinated SJL mice were completely protected against experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein peptide (PLP 139–151), and a monoclonal anti-IL-17A Ab (MM17F3), derived from C57Bl/6 mice vaccinated against IL-17A-OVA, also prevented disease development. Here we report that this Ab also protects C57Bl/6 mice from myelin oligdendrocyte glycoprotein (MOG)-induced EAE. Histological analysis of brain sections of C57Bl/6 mice treated with MM17F3 showed a complete absence of inflammatory infiltrates and evidence for a marked inhibition of chemokine and cytokine messages in the spinal cord. These results further extend the analytical and therapeutic potential of the autovaccine procedure.
|
 |
 |
