Type IIFN modulates the immune response induced by DNA vaccination to pseudorabies virus glycoprotein C

DNA vaccines have the capacity to induce strong Th1-biased immune responses that are of major importance to providing protection against intracellular pathogens. In the present study we have focused on the role played by type I IFN in immune responses induced after DNA vaccination. Mice lacking the IFNAR1 chain of the type I IFN receptor (IFNAR K/O mice) were immunized wit h a plasmid encoding glycoprotein C of pseudorabies Virus (PRV-gC). After D NA vaccination, wild-type (WT) mice showed features characteristic of Th1 i mmune responses, such as high IgG2a:IgG1 anti-PRV Ab ratio and antigen-spec ific IFN-gamma production by spleen cells. In contrast, IFNAR K/O mice show ed a significantly lower IgG2a:tgG1 Ab ratio and IFN-gamma production. In a ddition, the percentage of CD8(+) and B lymph-node cells expressing CD69 af ter PRV-gC DNA vaccination was lower in IFNAR K/O than in WT mice. These re sults support a major role played by type I IFN in shaping Th1 immune respo nses after DNA vaccination. Codelivery of plasmids encoding IL-12 and IL-18 along with the plasmid encoding PRV-gC restored Th1 responses in IFNAR K/O mice, (C) 2001 Academic Press.