Friday, May 9, 2025 5/9/2025

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

Award Number: K23AI163343
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

Group Awards By:

View Award Description

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $189,432 )
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	5	1/22/2025	NON-COMPETING CONTINUATION	$189,432
														Subtotal = $189,432

Issue Date FY: 2024 ( Subtotal = $189,432 )
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	1/4/2024	NON-COMPETING CONTINUATION	$189,432
														Subtotal = $189,432

Issue Date FY: 2023 ( Subtotal = $189,432 )
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	3	1/25/2023	NON-COMPETING CONTINUATION	$189,432
														Subtotal = $189,432

Issue Date FY: 2022 ( Subtotal = $189,431 )
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	2/7/2022	NEW	$189,432
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	1	5/27/2022	NEW	-$157,861
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	002	2	5/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$157,860
2022	2022	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	003	1	8/29/2022	NEW	-$8,699
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	004	2	8/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$8,699
														Subtotal = $189,431

Grand Total All Awards = $757,727

Top

All Categories

About

Search

Reports

Data Submission

Award Information

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

Award Number: K23AI163343

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer