Clinical Core

CLINICAL CORE: PROJECT SUMMARY The main goal of this research program is to obtain in-depth profiles human innate and adaptive immune cells responses to viruses in different tissues relative to circulating immune processes in blood. We will specifically investigate how site impacts the function, distribution and compartmentalization of innate and adaptive immune responses to multiple types of acute and persistent viruses. We will focus on assessing immune responses to viruses which are ubiquitous among the human population, including CMV, influenza, SARS-CoV-2, and also compare infection- and vaccine-generated responses to similar viruses. The program will use the tissues and cells obtained in the Clinical Core to profile T lymphocyte and dendritic cell (DC) responses in multiple lymphoid and mucosal tissue sites obtained from organ donors to assess the nature of the tissue immune response and its inherent differences from blood. In addition, we will assess immune response to vaccines in cohorts of individuals receiving immunomodulatory therapies which exhibit biased inhibition of circulating immune responses, including B cell depletion therapy and inhibitors of lymphocyte egress from lymphoid sites. In service aim 1, we will obtain and process multiple lymphoid and mucosal tissues from human organ donors, through our longstanding collaboration with LiveOnNY, the organ procurement organization for the New York metropolitan area, enabling tissues to be obtained form diverse populations. The core director will work with the fulltime procurement surgeon and co-investigator for the core to monitor the availability of organ donors, coordinate all of the protocols and MTAs necessary for maintaining the resource, acquire tissues from organ donors, and distribute samples to Project and core investigators. For service aim 2, we will obtain and process samples from healthy individuals and those on immune perturbation therapies cross sectionally and longitudinally following vaccination. We will assemble cohorts of healthy controls as well as persons with multiple sclerosis (MS) requiring immunomodulatory therapies and specifically via two mechanisms of action 1) peripheral B-cell depletion via anti CD20 monoclonal antibodies and 2) peripheral lymphocyte sequestration via sphingosine phosphate agonists. For each of these cohorts, cross sectional samples for in depth profiling of anti-viral immunity will be obtained, and longitudinal samples including samples pre and post vaccination with SARS-CoV-2 vaccines and seasonal influenza vaccines will be collected. In service aim 3, we will determine genotypes for all donors and cohorts in this study for ancestry determination to correlate potential functional variants in anti-viral immunity to genetic variations. Together, this Clinical core will be responsible for coordinating all of the personnel, institutional assurance, protocols and MTAs necessary to acquire and process human tissues, enroll and obtain samples from cohorts for longitudinal studies, and distribute samples to projects and cores.