An Ovalbumin-IL-12 Fusion Protein Is More Effective than Ovalbumin Plus Free Recombinant IL-12 in Inducing a T Helper Cell Type 1-Dominated Immune Response and Inhibiting Antigen-Specific IgE Production

Optimal treatment of allergic diseases requires that the cytokine profile of allergen-specific T cells be redirected, with the conversion of Th2 profiles into Th1 cytokine profiles. This conversion, however, is difficult, since Th2 effector cells have relatively fixed cytokine profiles. To more effectively redirect the cytokine profiles of T cells, we constructed a cytokine fusion protein that contained the Ag OVA, fused to IL-12. Immunization with the OVA-IL-12 fusion protein induced anti-OVA IgG2a Ab and large quantities of OVA-specific IFN-γ production. The Ag specificity of this response was dependent upon covalent linkage of Ag and IL-12, since immunization of mice with OVA alone induced little or no IFN-γ, while immunization with OVA and free rIL-12 enhanced T cell production of IFN-γ, but the IFN-γ production was not OVA specific. To examine the effects of OVA-IL-12 in reversing ongoing Th2-dominated immune responses, BALB/c mice previously primed with OVA in alum to induce a Th2-dominated response, were vaccinated with the OVA-IL-12 protein. In such mice, OVA-IL-12 was much more effective than OVA plus free rIL-12 in significantly increasing Ag-specific IFN-γ production and significantly decreasing Ag-specific IL-4 production. Moreover, OVA-IL-12 increased serum anti-OVA IgG2a and decreased anti-OVA IgE. These studies indicate that OVA-IL-12 can convert immune responses characterized by high IL-4 and high IgE synthesis into Th1-dominated responses in an Ag-specific manner.