Use of intranasal IL-12 to target predominantly Th1 responses to nasal andTh2 responses to oral vaccines given with cholera toxin

We have investigated the effects of IL-12 and cholera toxin (CT) on the imm une response to tetanus toroid (TT) given by intranasal or oral routes. CT inhibited IL-12-induced IFN-gamma secretion both in vivo and in vitro. Intr anasal administration of IL-12 to mice nasally immunized with the combined vaccine of TT and CT resulted in increased TT-specific IgG2a and IgG3 Abs, while IgG1 and IgE Ab responses were markedly reduced. This shift of the CT -induced immune response toward Th1 type was associated with TT-specific CD 4(+) T cells secreting IFN-gamma and reduced levels of Th2-type cytokines ( i.e., IL-4, IL-5, IL-6, and IL-10). In contrast, intranasal IL-12 enhanced the CT-induced serum IgG1 and IgE Ab responses in mice given the combined v accine orally. IFN-gamma secretion by TT-specific CD4(+) T cells was also e nhanced; however, Th2-type cytokine responses were predominant. Mucosal sec retory IgA responses to oral or nasal vaccines were not affected by intrana sal IL-12, Thus, intranasal IL-12 delivery influences Th cell subset develo pment in mucosal inductive sites that are dependent on the route of vaccine delivery.