Immune control of chronic viral infection in solid organ transplantation

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Principal Investigator: JONATHAN S MALTZMAN
Organization: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
Fiscal Year: 2024
Funding agency: Veterans Affairs

ABSTRACT
Immunosuppression required for lifesaving solid organ transplantation is complicated by significant
morbidity including increased recurrence of latent viral infection in transplant recipients. Approximately
60-70 percent of adults in the United States are latently infected with Cytomegalovirus (CMV). Control of
latent CMV depends on a continuously active immune response. In both healthy individuals and
immunocompromised transplant recipients, latent CMV has a profound effect of shaping the T
lymphocyte repertoire. We previously showed that the combination of immunosuppression and latent
CMV is sufficient to induce “accelerated” aging in the T cell compartment during the first year after kidney
transplantation. Immune aging or immunosenescence diminishes the capacity to respond to infection
and vaccination. However, whether the acceleration of aging continues to occur after the first year and
whether it is confined to the T cell compartment has not been studied. Our preliminary data suggests a
rapid aging of the B cell compartment over the first 2 years post-transplant as well as poor antibody
responses to vaccination in those with latent CMV. In this renewal, we hypothesize that latent CMV
continually shapes and ages the immune system in an accelerated manner after transplantation resulting
in diminished heterologous immune responses. Using a network of VA transplant centers and an
experienced team of transplant physicians and scientists, we will test this hypothesis with the following
specific aims: 1) determine the effect of latent CMV on immune aging in the B cell compartment, 2)
determine if accelerated inflation and aging continues after the first-year post- transplantation
and 3) determine whether immune changes induced by latent CMV can be used as predictors of
successful responses to SARS-CoV-2 booster vaccination responses. Results from these studies
will substantially expand our understanding of fundamental changes to the immune system induced by
CMV in the setting of solid organ transplantation thus providing critical knowledge that will aid in the care
of this at-risk Veteran population.

Terms: <21+ years old><Acceleration><Adult><Adult Human><Age><Aging><Antibody Response><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Booster Immunization><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CMV><COVID-19 booster><COVID-19 vaccination><COVID-19 vaccine booster><Cardiac Diseases><Cardiac Disorders><Caring><Cell Compartmentation><Cell Compartmentations><Cessation of life><Chronic><Cytomegalovirus><Data><Death><Drugs><ESRD><End stage renal failure><End-Stage Kidney Disease><End-Stage Renal Disease><Goals><Grafting Procedure><HCMV><Heart Diseases><Hepatic Disorder><Immune><Immune response><Immune system><Immunes><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunological response><Immunosuppressed Host><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Individual><Infection><Inflammation><Kidney Grafting><Kidney Transplantation><Kidney Transplants><Knowledge><Latent virus infection phase><Life><Liver diseases><Lung Diseases><Medication><Morbidity><Morbidity - disease rate><Older Population><Opportunistic Infections><Organ><Organ Transplantation><Organ Transplants><Patients><Pharmaceutical Preparations><Phenotype><Physicians><Population><Productivity><Pulmonary Diseases><Pulmonary Disorder><Recurrence><Recurrent><Regimen><Renal Grafting><Renal Transplantation><Renal Transplants><Risk><SARS-CoV-2 booster><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine booster><Salivary Gland Viruses><Scientist><Secondary Immunization><Severe acute respiratory syndrome coronavirus 2 vaccination><Shapes><Solid><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Testing><Transplant Recipients><Transplantation><United States><Vaccination><Vaccines><Veterans><Viral Diseases><Virus><Virus Diseases><Work><accelerated aging><accelerated biological age><accelerated biological aging><adulthood><age acceleration><age associated><age correlated><age dependent><age linked><age related><age specific><ages><booster against COVID-19><booster against SARS-CoV-2><booster vaccination><coronavirus disease 2019 vaccination><cytomegalovirus group><design><designing><disease of the lung><disorder of the lung><drug/agent><experience><experiment><experimental research><experimental study><experiments><heart disorder><hepatic disease><hepatopathy><host response><immune senescence><immune suppression><immune suppressive activity><immune suppressive function><immune system response><immunoresponse><immunosenescence><immunosuppressed patient><immunosuppressive activity><immunosuppressive function><immunosuppressive response><improved><kidney tx><latent viral infection><latent virus infection><liver disorder><lung disorder><military veteran><older groups><older individuals><older person><organ allograft><organ graft><organ xenograft><post-transplant><post-transplantation><posttransplant><posttransplantation><response><seropositive><thymus derived lymphocyte><transplant><transplant centers><transplant patient><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><veteran population><viral infection><virus infection><virus-induced disease>