Immune signatures of vaccine responses in children with sickle cell disease

PROJECT SUMMARY/ABSTRACT Our focus is identifying molecular signatures defining sickle cell disease and reduced vaccine response by investigating multiple components of innate immunity and the quality and quantity of long-term adaptive immunity among children with sickle cell disease. We propose a deep interrogation and a systems biology approach to characterize changes in innate and adaptive immunity and whole-genome transcriptional response induced by vaccination in a dysregulated inflammatory milieu linked to poor vaccine response. We have assembled an interdisciplinary investigative group who have an existing successful collaboration infrastructure and has expertise in human immunology, pediatric vaccine response, sickle cell disease, pneumococcal antibody response, proteomics, and computational biology to carry out the proposed studies by 1) examining the innate immune status of children with sickle cell disease; 2) elucidating innate and adaptive signatures of vaccination; 3) defining transcriptomic and proteomic signatures of vaccine response. We will leverage the recent advances in single-cell and spatial immune profiling methods and shared immunologic and proteomic platforms to create a novel resource for sickle cell disease patients and other vulnerable populations. We aim to provide comprehensive mechanistic insights into sickle cell disease-related chronic inflammation and impaired vaccine response that will lead to new interventions to improve clinical outcomes in this understudied pediatric population that have increased morbidity and mortality from infectious diseases and impaired responses to vaccination.