Development of an anti-IL-12 p40 auto-vaccine: Protection in experimental autoimmune encephalomyelitis at the expense of increased sensitivity to infection

IL-12 and IL-23, which share the IL-12 p40 subunit, have been ascribed central roles in many autoimmune disorders. We describe here an anti-IL-12 (αIL-12) auto-vaccine that potentially blocks both factors in vivo. Immunization of mice with mouse IL-12 coupled to OVA or Pan DR epitope (PADRE) peptide induced Ab directed against the IL-12 p40 subunit, which prevented IFN-γ production in response to IL-12 administration in vivo. Experimental autoimmune encephalomyelitis, an IL-23-dependent disease model, induced in SJL mice with a proteolipid protein (PLP) peptide was almost undetectable after αIL-12 vaccination. Myelin oligodendrocyte glycoprotein (MOG)-induced disease in C57BL/6 mice was also significantly inhibited. This protection correlated with inhibited Th1 cytokine responses in vitro and with an increase in the IgG1/IgG2a anti-PLP Ab balance. Detrimental consequences of αIL-12 vaccination were evaluated in C57BL/6 mice infected with Leishmania major (L.m.). While delayed-type hypersensitivity (DTH) suppression and immunoglobulin as well as interleukin production patterns reflected a major shift toward a Th2-type response, L.m. growth was still significantly retarded as compared to that seen in susceptible BALB/c mice. However, vaccinated animals ultimately failed to control parasite expansion. These results suggest that some chronic autoimmune diseases may benefit from αIL-12 vaccination at the expense of reduced, but not completely abrogated, cell-mediated immunity. © 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.