Rational adjuvant selection for the neonatal period shapes unique and lasting immune polarization in mice

A major knowledge gap exists in understanding immune effects of adjuvants in early life. As environmental stimuli shape the infant immune system, adjuvants may also influence this process. Using a neonatal mouse model, we investigated the differential effects of adjuvants in neonates vs. adults. Mice were immunized with an adjuvanted hepatitis B vaccine followed by exposure to ovalbumin to determine whether prior immunization alters subsequent heterologous immune responses. Neonatal immunization with a Th2-biased alum-adjuvanted vaccine predisposed mice to develop Th2-biased immunity to subsequent ovalbumin exposures. Conversely, neonatal immunization with a Th1-polarizing CpG-adjuvanted vaccine resulted in preferential priming of Th1-biased heterologous responses. Immunization in adulthood did not alter heterologous immune responses. Early-life immunization modified the ability of bone marrow DCs to prime Th1/Th2 immune responses, suggesting a role for immune training in these antigen agnostic effects. These data suggest that rational adjuvant selection for early-life vaccines may beneficially shape immune development.