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Trained immunity in the prevention of viral myocarditis and pancreatitis

Award Number: R21AI166773
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/01/2021
PERIOD OF PERFORMANCE END DATE: 10/31/2025

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Trained immunity in the prevention of viral myocarditis and pancreatitis - PROJECT SUMMARY/ABSTRACT Enteroviruses, such as group B Coxsackieviruses, are common suspects in myocarditis and pancreatitis. However, no vaccines are currently available for these viruses, in part because multiple serotypes of Coxsackieviruses can induce similar diseases. Thus, exploration of alternative strategies to protect against them may have merit. The research team has made an unexpected observation that animals immunized with complete Freund’s adjuvant (CFA) were completely protected from both myocarditis and pancreatitis induced with Coxsackievirus B3 (CVB) pointed to a possibility that trained immunity may be an underlying mechanism of CFA-mediated effects, as demonstrated with the Bacillus Calmette-Guérin (BCG). The long-term goal of this research is to identify adjuvants that induce trained immunity to enhance anti-viral vaccine responses in the prevention of enteroviral infections. The objective of this application is to determine if macrophages primed with CFA mediate trained immunity. The central hypothesis is that the CFA contributes to the induction of anti-viral responses by trained immunity. This hypothesis will be tested by two specific aims: 1) characterize anti-viral responses in animals immunized with CFA and 2) determine the mechanisms of CFA- mediated protection in CVB infection. Methods and tools to be used include multiplex cytokine bead array, virus neutralization test, and major histocompatibility complex class II dextramers to assess antigen-specific immune responses and chromatin immunoprecipitation and metabolite assays to investigate the mechanisms of CFA-induced trained immunity. The project is innovative because it aims to determine whether trained immunity offers protection against CVB infections. The proposed studies are significant because they will: 1) mechanistically investigate whether trained immunity is sufficient to prevent enterovirus infections and 2) identify pathways that contribute to CFA-induced trained immunity. These outcomes may have a significant impact on strategies for preventing and/or treating viral infections using mycobacterial components that are known to possess immune-stimulating properties.


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: 2026 ( Subtotal = $0 )
2026	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST # 830861	LINCOLN	NE	68503	LANCASTER	USA	Allergy and Infectious Diseases Research	000	2	4/24/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST # 830861	LINCOLN	NE	68503	LANCASTER	USA	Allergy and Infectious Diseases Research	000	2	12/2/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $180,736 )
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Allergy and Infectious Diseases Research	000	2	10/20/2022	NON-COMPETING CONTINUATION	$180,736
														Subtotal = $180,736

Issue Date FY: 2022 ( Subtotal = $217,570 )
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Allergy and Infectious Diseases Research	000	1	10/27/2021	NEW	$217,570
														Subtotal = $217,570

Grand Total All Awards = $398,306

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Trained immunity in the prevention of viral myocarditis and pancreatitis

Award Number: R21AI166773

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 11/01/2021

PERIOD OF PERFORMANCE END DATE: 10/31/2025

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