Immune signatures of vaccine responses in vulnerable populations

ABSTRACT OF PARENT AWARD: We molecular with These responsiveness. longstanding understudied responsiveness. different deeply mathematical determine effectiveness. shared characterizes development therapeutic propose a deep interrogation and a systems approach that will identify signatures to vaccination across three cohorts of vulnerable patient populations: autoimmune patients B cell depletion, aged and frail individuals, and patients with sickle cell disease who are f unctionally asplenic. distinct populations share a dysregulated inflammatory milieu that is linked to poor vaccination We have assembled an interdisciplinary team of investigators with a track record of and productive ollaborations. We use a systems approach t hat combines well-defined and cohorts with unbiased large-scale profiling to elucidate signatures defining vaccine This goal wil l be accomplished by 1) examining three vulnerable patient cohorts challenged with vaccines, i ncluding novel mRNA vaccines nd ne shared vaccine; 2) using shared platforms that interrogate immune responses f rom blood and limited-access compartments, and 3) refining new tools for multidimensional analysis of data to identify active pathways and modules and to specific connections among components in the immune network that contribute to differential vaccine This effort capitalizes on recent advances in single-cell and spatial immune profiling methods and immunologic and proteomic platforms to create a novel public resource for vulnerable populations that diverse states of the human immune system. Integration across our cohorts will support the of molecular signatures of vaccination responses and identify critical pathways relevant to potential strategies.