Abstract
Global implementation of messenger RNA (mRNA) vaccines represents an enormous advance with far-reaching implications for respiratory disease treatment. mRNA vaccines offer exceptional efficacy and versatile capacity to be adapted to new viruses and variants; however, critical questions remain regarding immune persistence and formulation stability. This represents a significant opportunity for developing next-generation, inhaled mRNA vaccines with the ability to drive long-lasting, tissue-specific memory responses needed for rapid recall and immediate local protection. Advances in pulmonary delivery technologies offer potential to overcome translational challenges including design of aerosol-stable and lung-stable formulations, navigation of pulmonary biological barriers, and a lack of predictive models and measurement techniques. We highlight recent advances in each of these challenge areas to illuminate the path to translation.