IL-12 is a potent neonatal vaccine adjuvant

Neonatal animals show generally poor responsiveness to foreign antigens and are known to display polarized expression of Th2-like cytokines and antibo dy responses. We now report that newborn mice display a reduction in periph eral expression of the Th1-inducing cytokine, IL-12. Attempts to overcome t his decrease by immunization and treatment with IL-12 within 24 h of birth resulted in elevated levels of IFN-gamma and IL-10 mRNA in the spleens of m ice compared to animals exposed to antigen only. Moreover, such animals sho wed dramatic enhancement of IgG2a and IgG2b antibody levels upon adult chal lenge compared to mice primed with antigen alone. These effects appeared to be due to induction of neonatal B cell memory. IgG1 antibody levers, a mea sure of Th2 activity, were unaffected or even somewhat enhanced by neonatal IL-12 treatment. Taken together, these results provide evidence that IL-12 administration induces a Th1-like cytokine response in newborns and causes priming for heightened memory antibody responses in vivo. Our findings sug gest the use of IL-12 as a vaccine adjuvant in neonates for inducing protec tion against common childhood pathogens.