Abstract Objective of this proposal is to engineer a Powder-Laden, Dissolvable MicroNeedle Array (PLD-MNA) to improve newborn Hib vaccination. Due to the immature immune system, most of the newborn vaccines induce suboptimal immune responses and require multiple boosters to induce a protective immunity. The lengthened vaccination schedule, in conjunction with a rapid decline of maternal antibodies after birth, leaves a few months of a vulnerability period to various infections for every newborn, which is the single major factor for a high rate of vaccine- preventable diseases occurring in newborns. To eliminate or greatly shorten the vulnerable period, we identified a potent adjuvant cGAMP, an agonist of the stimulator of IFN genes (STING) that could robustly bolster adaptive immune responses in neonatal mice. We will combine this potent adjuvant and powder-based epidermic vaccination to vigorously augment Hib vaccine and reduce Hib vaccine dosage from the current 4 to 2 doses in this proposal. We will first fabricate PLD-MNA encapsulated with Hib conjugated PRP-T vaccine and cGAMP and characterize its loading capacity and delivery efficiency in both newborn mice and piglets. We will also minimize skin irritation, if there is any, in a piglet model and optimize the dosage of immunization in newborn mice. Aim 2 will validate whether prime at birth and boost 10 days later with PLD-MNA packaged with PRP-T/cGAMP can induce a comparable or superior immune response than four alum/intramuscular immunizations of PRP-T vaccine in the presence of maternal antibodies. This needle-free, potentially home-use vaccination, if successful, would represent a paradigm-shifting technology to augment many vaccines for newborns and infants, because most of current infant vaccines are made in a form of powder and can be directly loaded into the PLD-MNAs and applied to newborns.