Immune trajectories across the first year of life

PROJECT 2 - PROJECT SUMMARY Defining unique features of immune cells and their responses in infants is critically important to provide tailored approaches to vaccination and immunomodulation that takes into account the fact that early-life immune responsiveness differs significantly from adults in nuanced but important ways. Pediatric immunology has traditionally been hampered by challenges surrounding in-depth analyses of small-volume blood samples; however, cutting-edge approaches now enable unparalleled depth of biological information to be gleaned from a limited number of single-cells or serum volume. Here, we have strategically crafted a longitudinal analysis of homeostatic baseline and how these are altered by prematurity and natural infection-induced immune profiles across the first year of life. We will leverage multi-omic single-cell studies with antigen receptor repertoire analyses, serum proteomics, antibody target profiling, and functional studies to characterize immune states in early life and test the hypothesis that environmental cues coupled with developmentally tuned cellular metabolism drive unique biology of immune cells in early life that is dynamically altered by natural infections and prematurity. We will test this hypothesis in two aims: (Aim 1) will systematically define adaptive immune cell development while (Aim 2) will illuminate innate immune remodeling across the first year of life and how these processes are altered by prematurity and infections. Together, these data will not only provide a critical resource of multi-dimensional data for the field to leverage broadly but also enable testing of our hypotheses about molecular drivers of immune maturation and immunological memory.