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Issued by

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

This Request for Information (RFI) is intended to solicit input from the radiation biology and microbiome research communities regarding the state of the science of the interplay between radiation exposure and the microbiome, including, but not limited to, the impact of radiation on the known microbiome niches in the human body (e.g., skin, oral mucosa, gastrointestinal (GI) tract, lungs), microbiome signatures that may predict susceptibility or resilience to radiation injury, and/or microbiota-based or microbiota-targeted radiation medical countermeasures (MCMs). The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) will use the information obtained in response to this RFI to develop recommendations for future programs to support research and development of effective and safe radiation MCMs and/or identification of biomarkers and biodosimetry tools targeting/using the microbiome.

Background

The Department of Health and Human Services (HHS) is charged with protecting the civilian population by providing leadership in research, development, acquisition, deployment, and use of effective MCM for Weapons of Mass Destruction. The HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Implementation Plan for Chemical, Biological, Radiological and Nuclear (CBRN) Threats provides a blueprint for all of its MCM-related activities. Among the top priorities identified by the HHS PHEMCE Implementation Plan are MCMs to address injuries resulting from exposure to radiological and nuclear threats. NIAID has been charged to develop and manage a comprehensive research and early product development program focused on medical therapies and diagnostics, as initially set by NIH Strategic Plan and Research Agenda for Medical Countermeasures against Radiation and Nuclear Threats, and updated in 2012.

The Acute Radiation Syndrome (ARS) defines a spectrum of organ damage caused by exposure to high doses of penetrating radiation. The level of injury depends on the radiation dose, dose-rate, and whether the exposures are whole body or partial body. Radiation exposures exceeding 2 Gy in adults can result in the depletion of hematopoietic stem cells and cellular progenitors in the bone marrow, which may lead to severe neutropenia, thrombocytopenia, and death. As of early 2021, four products - Neupogen®, Neulasta®, Leukine®, and Nplate® - have been approved by the U.S. Food and Drug Administration (FDA) to treat these hematopoietic complications. Exposure to higher radiation doses can cause GI complications, including mucosal barrier breakdown, bacterial translocation, and loss of GI structural integrity, which can lead to rapid death. Furthermore, victims who survive ARS may suffer from late effects, which include pulmonary, renal, cardiac, and cutaneous complications occurring weeks to months after radiation exposure. No products are yet approved to treat these other injuries, and no radiation biodosimetry tests have yet been cleared by the FDA for triage or dose assessment.

Understanding the role of the microbiome in radiation pathogenesis, assessment of exposure, protection, mitigation, and/or exacerbation of injury following radiation exposure is of great interest. Such studies may help reveal new mechanisms of action, MCMs, and biomarkers for biodosimetry to be used in the event of a radiation public health emergency. Radiation exposures experienced during a radiological or nuclear incident will likely vary widely from low to high dose and could involve a variety of dose rates and radiation exposure scenarios, for example, from prompt gamma and/or neutron exposure, or from internalized radionuclides. Research to understand the complexities of the body’s resident microbiota and their pathogenesis in radiation injury is needed to help fill knowledge gaps in current understanding of these topics. This relatively new area of research could lead to exciting new drug targets, MCMs, and novel microbiome-based biomarkers of radiation injury. To establish the state of the science and facilitate research on radiation and the microbiome, the NIAID is looking for information on institutional expertise in:

• The microbiome in the various organ tissues of the body, and their involvement in radiation pathogenesis in those tissues and organs affected by total and/or partial body radiation exposure.
• Studies of radiation effects on the microbiome in animal models.
• Identification and demonstration of efficacy of MCM candidates targeting the microbiome or the immune system’s interaction with the microbiome, with regard to the following criteria

• • Must be effective when administered at least 24 hours post-irradiation;
  • Must be relevant to an attack or accidental exposure incident in terms of radiation exposure type, dose level, and dose rates proposed for the study;
  • Demonstrate ease-of-use in a mass casualty setting (i.e., route of administration is oral, subcutaneous, intramuscular, inhaled, topical, transdermal, etc.);
  • Have a favorable safety profile.

Information Requested

All stakeholders within the radiation biology and microbiome research communities are invited to respond. Areas of interest include, but are not limited to:

• Research on microbial changes following radiation exposure that could be used as biomarkers of injury/biodosimeters;
• Studies of differing microbiomes in strains and species linked to susceptibility or resistance to radiation injury;
• Model development to study effects of radiation exposure on the microbiota located across the body of interest for a public health emergency (e.g., GI tract, oral mucosa, lung, skin);
• Development of MCMs targeting the microbiome to prevent or mitigate radiation injury, when administered >24 hours post-irradiation, such as:

• • Probiotics or genetically modified bacteria, dietary modifications, prebiotics, vitamins, and minerals
  • Fecal microbiota transplant
  • Antibiotic approaches
  • Other products that exert an effect on the microbiome or the body’s immune response to changes in the microbiota

How to Submit a Response

RFI responses should be directed to Andrea DiCarlo, Ph.D., NIAID Division of Allergy, Immunology and Transplantation (DAIT), Radiation and Nuclear Countermeasures Program (RNCP) via e-mail at [email protected] by August 15, 2021.

Responses should be limited to 2 pages and emailed as an attachment (Microsoft Word or PDF). No proprietary, classified, confidential, or sensitive information should be included in your response. Submitted data and information will not be returned and will not be considered confidential.

Responses to this RFI are voluntary. This RFI is for planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Federal Government, NIH, or NIAID. NIH does not intend to make any awards in response to this RFI or to pay for either the preparation of information submitted or the Government’s use of such information.

Citations:

1. Parker, Gerald, DVM. HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Implementation Plan for Chemical, Biological, Radiological and Nuclear Threats. Federal Register / Vol. 72, No. 77 April 23, 2007.

2. National Institute of Allergy and Infectious Diseases, U.S. Department of Health and Human Services. NIH Strategic Plan and Research Agenda for Medical Countermeasures against Radiological and Nuclear Threats. 2005.

3. National Institute of Allergy and Infectious Diseases, U.S. Department of Health and Human Services. Strategic Plan and Research Agenda for Medical Countermeasures against Radiation and Nuclear Threats Progress Report: 2005–2011 and Future Research Directions: 2012–2016. 2012.

4. Hollingsworth BA, Cassatt DR, DiCarlo AL, Rios CI, Satyamitra MM, Winters TA, Taliaferro LP. Acute Radiation Syndrome and the Microbiome: Impact and Review. Frontiers in Pharmacology. ePub ahead of print 18 May 2021. doi: 10.3389/fphar.2021.643283.

Inquiries

Please direct all inquiries to:

Andrea DiCarlo, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3492
Email: [email protected]