Neonatal administration of IL-12 enhances the protective efficacy of antiviral vaccines

Neonates are highly susceptible to infectious agents and are known to displ ay polarized expression of Th2-like cytokines and Abs. This neonatal immune bias has important implications for the development of vaccine strategies, particularly against viral in fections, We now report that coadministratio n of IL-12 and an influenza subunit vaccine at birth enhances the protectiv e efficacy of antiviral vaccination. Immunization and treatment with IL-12 within 24 h of birth resulted in elevated expression of IFN-gamma IL-10, an d IL-15 mRNA in the spleens of newborn mice compared with animals exposed t o vaccine only. In addition, these animals showed dramatic increases in IFN -gamma-, IL-2-, and IL-4-secreting cells, and in IgG2a Ab levels upon adult challenge compared with mice primed with vaccine alone, Most importantly, animals vaccinated and simultaneously treated with IL-12 at birth displayed enhanced survival after lethal challenge with infectious influenza virus a s adults compared with infected animals that had been primed with vaccine a lone. This augmented protection required B cells and could be transferred t o naive mice by immune serum. Collectively, these results provide evidence that administration of IL-12 to neonates Induces a Th1-like response in new borns and elicits protective antiviral immune memory.