Address Research Gaps in Radiation-Induced Immune Dysfunction

Can you help NIAID’s Radiation and Nuclear Countermeasures Program (RNCP) address knowledge gaps in understanding mechanisms of injury and repair resulting from radiation-induced immune system dysfunction? If so, apply for support through the new funding opportunity announcement (FOA) Radiation-Induced Immune Dysfunction (U01, Clinical Trial Not Allowed) to help develop new radiation medical countermeasures (MCMs) and identify novel biomarkers of injury.

Research Objectives and Scope

The RNCP supports research and development of MCMs to mitigate and treat acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE), and to identify biomarkers of injury for triage and patient management following a radiological or nuclear incident.

Through this initiative, the RNCP will support development of animal models for immune-targeted radiation injuries, studies to better understand radiation impacts on the immune system (including immune system-mediated multi-organ injury), identifying immune-specific pathways targeted by radiation, as well as biomarkers of exposure and mitigators/treatments that target immune-related response pathways.

The research should be consistent with FDA’s Product Development Under the Animal Rule Guidance Document, issued in October 2015. In most cases, licensure or approval of radiation MCMs will occur in accordance with the FDA Animal Rule codes 21 CFR 314.600 Subpart I for drug products and 21 CFR 601.90 Subpart H for biologic products; CFR—Code of Federal Regulations Title 21. 

Research Areas of Interest

Below are examples of NIAID’s research areas of interest. Refer to the FOA linked above for the complete list.

• Examine early and late hematological complications of radiation injury related to bone marrow-residing immune cells and the niche environment
• Evaluate local and systemic, immediate, and delayed inflammatory responses involving immune cells
• Examine the effects of radiation on innate or adaptive immunity, and recovery or residual damage to the immune system, including persistence or loss of memory cell functions
• Evaluate candidate therapies that target immune dysfunction, such as enhancing post-irradiation innate and adaptive immunity recovery or managing the inflammatory response to radiation injury. Candidate therapies are to be tested in appropriate in vivo models that demonstrate desired endpoints for humans when administered 24 hours or more post-irradiation.

Research approaches within those topic areas may include:

• Animal model development and mechanism of action studies
• Routes of MCM administration with an emphasis on oral, subcutaneous, intramuscular, or topical delivery
• Early- to mid-stage research in preclinical development of immune-system-targeted therapies to treat radiation-induced injuries to different organ systems
• Establishing endpoints applicable to human studies (e.g., prevention of major morbidities or increased survival) for the appropriate model system selected as well as use of standard medical management approaches connected to any potential therapy

Nonresponsive Research Areas

If your application includes the following research areas, NIAID will consider your application nonresponsive and not review it. Read the FOA linked above for the complete list of nonresponsive research areas.

• Radiation dose ranges or exposure parameters that are not relevant to a radiation accident (e.g., studies using fractionated radiation exposures or very low-dose/low-dose rate exposures that do not elicit ARS)
• Biodosimetric studies designed solely to determine endpoints of exposed radiation dose or dose exposure range
• Administering candidate products at times earlier than 24 hours post-irradiation, including pre-irradiation exposure
• Radiation-induced carcinogenesis
• Studies focused on HIV/AIDS-related research

Milestones

Applicants should note that a milestone-based approach is required as part of the research project. NIAID program staff will use these explicit, detailed, quantitative, annual milestones to assess annual progress and recommend continued funding. 

Cooperative Agreements and Research Project Grants

For more information on how cooperative agreements differ from research project grants, read Cooperative Agreements (U).

Deadline and Contact Information

Application budgets are not limited but must reflect the actual needs of the proposed project. The scope of the proposed project determines the project period, which cannot exceed five years. 

All applications are due on August 24, 2021, by 5 p.m. local time of the applicant organization.

Direct any research questions to Dr. Thomas Winters, NIAID’s research contact for this initiative, and any review questions to Dr. Kelly Hudspeth, the initiative's peer review contact.