Core B: Clinical Core

Project Summary Translational research is critically dependent on availability of adequate specimens from well-defined clinical cohorts of patients. This Clinical Core builds and maintains such cohorts and facilitates a broad array of studies in human immunology. During the past three cycles of our consortium, we successfully recruited and enrolled over two thousand subjects, leveraging two paradigm-shifting therapeutic advances of this century: effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and immune checkpoint inhibitors (ICIs), particularly targeting the PD-1 axis, for cancer. These developments allowed unique opportunities to study the scars left by human chronic viral infection and to explore the reversal of T-cell exhaustion and resetting of immunity. We can further capitalize on “the human experiment” by dissecting immune mechanisms in humans where a single immune pathway involved in the germinal center response can be interrogated by capturing standard of care vaccination in patients receiving αPD-1. Finally, during the last cycle a global immunological challenge in the COVID-19 pandemic spurred a third major advance of this century: the introduction of SARS- CoV-2 mRNA vaccines. While their biology and clinical courses differ, SARS-CoV-2 and HCV are each RNA viruses where immune responses and outcomes can be compared. Moreover, we can dissect differences between immune responses to vaccination for Flu and SARS-CoV-2. Samples collected by the Clinical Core will allow examination of three areas of immunobiology: 1) investigation of persisting virus and immune dysfunction in post-acute sequelae of PASC; 2) interrogation of immune scarring after cure of a persisting infection, and 3) dissection of an immunoregulatory pathway associated with persisting infections for its role in vaccine-induced adaptive immune memory. Integration of findings across these areas is a distinct advantage of this Immune Perturbation Study Group (IPSG), empowered by this Clinical Core and its relevant cohorts and large numbers of well-annotated samples. By supporting the studies described in the Projects and the Immune Health Core, this Core will facilitate a novel and integrated examination of human immune responses to viral pathogens and to their vaccines in the context of three key perturbations: PASC, HCV infection and specific immune manipulation via αPD-1.