# Immune control of chronic viral infection in solid organ transplantation

> **NIH VA I01** · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · 2024 · —

## Abstract

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.

## Key facts

- **NIH application ID:** 10928049
- **Project number:** 2I01CX001971-05
- **Recipient organization:** VETERANS ADMIN PALO ALTO HEALTH CARE SYS
- **Principal Investigator:** JONATHAN S MALTZMAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2019-10-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928049

## Citation

> US National Institutes of Health, RePORTER application 10928049, Immune control of chronic viral infection in solid organ transplantation (2I01CX001971-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10928049. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*