Anti-IL-17A autovaccination prevents clinical and histological manifestations of experimental autoimmune encephalomyelitis.
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.
Uyttenhove
Catherine
C
Ludwig Institute for Cancer Research, Brussels Branch, 74 av. Hippocrate UCL 7459, B-1200 Brussels, Belgium. catherine.uyttenhove@bru.licr.org
Sommereyns
Caroline
C
Théate
Ivan
I
Michiels
Thomas
T
Van Snick
Jacques
J
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D007167:Immunotherapy; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination
D016207:Cytokines; D020381:Interleukin-17