# Cytomegalovirus-specific Immune Reconstitution after Hematopoietic Cell Transplantation in the Era of Modern Antiviral Prophylaxis

> **NIH NIH K23** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2022 · $31,571

## Abstract

Project Summary/Abstract
Cytomegalovirus (CMV) is one of the most important causes of infectious complications following hematopoietic
cell transplantation (HCT). Letermovir is an effective antiviral and was recently approved for prophylaxis to
prevent CMV reactivation after HCT. Graft-versus-host disease (GVHD) prophylaxis has advanced alongside
CMV prophylaxis, but the effects of novel GVHD therapies on infectious complications and immune reconstitution
patterns are unclear. Current data suggest that modern GVHD prophylaxis with post-transplantation
cyclophosphamide and sirolimus may offer an immunologic advantage over traditional prophylaxis with
calcineurin inhibitors. In this proposal, Dr. Zamora will prospectively examine how these GVHD prophylaxis
strategies influence CMV-specific T-cell and humoral immunity after HCT, and how these immunological
changes can affect overall clinical outcomes.
In the first aim of this proposal, Dr. Zamora will examine the effects of viral, host, and transplantation factors,
including GVHD prophylaxis, on polyfunctional CMV-specific cellular immune reconstitution. He will use
advanced analytical methods to compute polyfunctional T-cell responses and compare differences in immune
responses between GVHD prophylaxis regimens. Dr. Zamora will also compare the accuracy of these analytical
methods, versus traditional methods of measuring polyfunctionality, in predicting late clinically significant CMV
infection after HCT. Furthermore, he will study the immunologic influence of regulatory T cells on the
development of polyfunctional T-cell immune reconstitution after HCT and investigate whether this may be
affected by the presence or absence of CMV reactivation.
Historically, humoral immunity was not felt to be important in CMV prevention after HCT; however, recent animal
studies have challenged this notion. Therefore, in the second aim Dr. Zamora will characterize factors influencing
functional CMV-specific humoral immune reconstitution after HCT, using state-of-the-art neutralizing antibody
and cell-to-cell spread inhibition assays. He will also evaluate the kinetics of CMV-specific antibody responses
at the epitope level, using a novel serological profiling technology that can detect antibody responses to
thousands of pathogen epitopes (VirScan). Dr. Zamora will investigate the associations of CMV-specific humoral
immunity, as measured by these novel immune platforms, with the prevention of late clinically significant CMV
reactivation after HCT.
Dr. Zamora aims to define CMV-specific T-cell and humoral immune reconstitution kinetics in the current era of
advanced GVHD prophylaxis regimens and effective antiviral prophylaxis. This study has the potential to define
immunologic parameters to optimize CMV prophylaxis strategies and provide the basis for novel immunotherapy
and immune monitoring approaches.

## Key facts

- **NIH application ID:** 10449907
- **Project number:** 1K23AI163343-01A1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Danniel Zamora
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,571
- **Award type:** 1
- **Project period:** 2022-02-07 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449907

## Citation

> US National Institutes of Health, RePORTER application 10449907, Cytomegalovirus-specific Immune Reconstitution after Hematopoietic Cell Transplantation in the Era of Modern Antiviral Prophylaxis (1K23AI163343-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10449907. Licensed CC0.

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