Development of an anti‐IL‐17A auto‐vaccine that prevents experimental auto‐immune encephalomyelitis

Abstract

IL-17 has been associated with multiple inflammatory disorders such as rheumatoid arthritis, asthma and multiple sclerosis. As these diseases require long-term treatment we turned to an auto-vaccine strategy for IL-17 neutralization in vivo. Mouse IL-17A was covalently linked to ovalbumin and used to immunize C57BL/6 mice. This vaccine induced the production of antibodies that blocked IL-17A bioactivity in vitro but did not react with the other IL-17 isoforms, including IL-17F. As the half-life of the Ab titers after the last immunogen administration was approximately 4 months, the vaccine provides for long lasting and selective inhibition of IL-17A activity in vivo. A monoclonal Ab (mAb) derived from these mice showed the same specificity for IL-17A. To test the ability of the vaccine to confer protection against an IL-17-dependent disorder, SJL mice were vaccinated with IL-17-OVA and encephalomyelitis (EAE) was induced by proteolipid protein (PLP) peptide 139-151. Vaccinated mice were completely protected against the disease. The above-mentioned anti-IL-17A mAb also prevented EAE development. The absence of clinical symptoms contrasted with unaltered PLP-induced cytokine production in vitro and unmodified anti-PLP IgG titers and isotypes. These results suggest that an anti-IL-17A auto-vaccine offers new perspectives for therapy of autoimmune diseases.

Absence of IL-23p19 in donor allogeneic cells reduces mortality from acute GVHD

“…One of these is the seminal role that IL-23 dimer, termed p19, may have in the pathogenesis of aGVHD. The results presented herein and in the literature suggest two new approaches to therapy, that is, preventive antibody therapy directed at IL-17 57 and IL-23p19. 13,58 …”

Auto-vaccins

“…Nous avons également amélioré nos vaccins en déve-loppant une forme polymérique d'ovalbumine couverte de glutaraldéhyde (OVAglu) capable de se coupler aux groupements aminés présents sur les protéines cibles. Grâce à ce polymère OVAglu, nous avons développé des auto-vaccins contre l'IL-17 [19], le GM-CSF (granulocyte macrophage colony stimulating factor), l'IL-25, le TGF-β1 (transforming growth factor b1), l'IL-27 p28 (IL-30), la chimiokine CXCL6/GCP-2 (granulocyte chemotactic protein-2) et la métalloprotéase MMP9 [20]. Une autre forme de transporteur très efficace pour obtenir une auto-vaccination est constituée par les VLP (viral like particles).…”

Les kinoïdes

“…Notons que le KLH est actuellement utilisé à des doses élevées comme immunostimulant dans des essais cliniques en cancérologie (cancer de la vessie) [17]. D'autres agents de couplage, comme le carbodiimide, ou d'autres protéines porteuses, comme l'ovalbumine, ont été utilisés pour produire avec succès des kinoïdes dirigés contre l'IL-9 et l'IL-17 [18,19]. D'autres vaccins kinoïdes ont été préparés à partir d'immunogènes constitués d'un pool de protéines mutées analogues de la cytokine IL-6 native [20], ou encore à partir de vecteurs auxiliaires lipidiques tels que les VLP (virus like particles) anti-TNF (tumor necrosis factor) [21].…”