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Harnessing Trained Immunity as a Radiation Medical Countermeasure

Award Number: U01AI186972
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/24/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2030

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Harnessing Trained Immunity as a Radiation Medical Countermeasure - Radiation exposure causes acute and chronic injuries to cells, tissues, and organs that induce inflammatory and immune complications. Among the most serious complications is predisposition to life-threatening opportunistic infections due to hematopoietic and immune system damage. Long term effects referred to as delayed effects of acute radiation exposure (DEARE) can also occur leading to progressive organ system failure and increased risk of developing cancer or other chronic diseases. Our radiation MCM development research program centers on the concept of targeting innate immune pathways to induce protective anti-microbial immunity and restore immune system homeostasis. We discovered that treating mice with CpG-DNA, a Toll-like receptor 9 (TLR9) agonist found in bacteria and mitochondria, can restore anti-microbial immune function in mice exposed to immune-compromising total body irradiation (TBI) radiation doses. CpG-DNA induces trained immunity in mice via a mechanism involving mesenchymal stromal cells (MSC) effects on hematopoietic stem cells (HSC). The immune regenerative activity of CpG-DNA enhances anti-microbial immunity and reduces DEARE. As such, this project will address the next phases of developing CpG-DNA as a MCM strategy for radiation as well as radiation with traumatic injury. Given the complexity of radiation and traumatic injuries, we will use systems biology research methods to explore detailed changes in the hematopoietic and immune system. To implement translational potential, male and female mice, and natural immune “dirty” mice will be included in the experimental design of these pre-clinical studies. We hypothesize that CpG-DNA treatment will help regenerate hematopoietic system recovery by acting on bone marrow hematopoietic and progenitor cells to promote early and late recovery responses in people that may be exposed to radiation with or without trauma. Project aims will (1) systematically test, develop, and optimize CpG-DNA MCM treatment approaches for radiation injuries, (2) identify functional effects of CpG-DNA MCM treatments on infection and immune system recovery after radiation with and without trauma, (3) discover molecular and cellular mechanisms involved in the immune regenerating activity of CpGDNA. We hypothesize that targeting innate pathways will signaling “upstream” networks to regenerate “downstream” injurious complications of radiation exposure by promoting homeostasis and recovery responses. We expect that the findings from this project will support future translation for CpG-DNA for use in immune compromised people exposed to radiation or other insults that suppress normal immune function and homeostasis.


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 = $610,700 )
2026	2026	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	2	8/10/2026	NON-COMPETING CONTINUATION	$610,700
2026	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	11/26/2025	NEW	$0
														Subtotal = $610,700

Issue Date FY: 2025 ( Subtotal = $586,619 )
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	9/24/2025	NEW	$586,619
														Subtotal = $586,619

Grand Total All Awards = $1,197,319

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Harnessing Trained Immunity as a Radiation Medical Countermeasure

Award Number: U01AI186972

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/24/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2030

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