Efficient induction of antigen-specific, T helper type 1-mediated immune responses by intramuscular injection with ovalbumin/interleukin-18 fusion DNA.

The balance of two types of T helper (Th) cells, Th1 and Th2 subsets, is important with respect to susceptibility or resistance to particular infections, or to autoimmune diseases and allergic diseases. To effectively induce Th1 immune responses in an antigen-specific manner, we constructed a mammalian expression plasmid (pOVA/IL-18) carrying a fusion gene in which the ovalbumin (OVA; a model antigen) cDNA was covalently linked to mature interleukin-18 (IL-18) cDNA. Intramuscular injection of C57BL/6 mice with the pOVA/IL-18 DNA efficiently increased the production of both OVA-specific IFN-gamma and anti-OVA IgG2a isotype, compared with the injection with the pOVA DNA. In addition, the pOVA/IL-18 was more efficient than a simple mixture of pOVA and pIL-18 in inducing antigen-specific, Th1 immune responses and in inhibiting OVA-specific, IL-4 production. These studies indicate that vaccination with the OVA/IL-18 fusion DNA efficiently induces Th1 immune response in an antigen-specific manner.