NIAID invites research applications to better understand the pathophysiology of long-term lung damage resulting from Mycobacterium tuberculosis (Mtb) and the role of the immune response during tuberculosis treatment through Notice of Special interest (NOSI): Establishing and Utilizing Preclinical Animal Models to Study Post-TB Lung Disease Development.
Mtb is a significant global health challenge that produces a spectrum of clinical states and disease in humans during both active disease and latent infection. Clinicians will base a treatment’s success or failure primarily on microbiological outcomes defined by sputum culture.
However, some cured patients are afflicted with irreversible lung damage and debilitating chronic lung function impairment that has come to be known as Post-TB Lung Disease (PTLD). While most of our understanding of PTLD comes from long-term human cohorts, using animal models for PTLD development could help address difficult mechanistic questions when relying solely on human studies. To prevent the long-term impact of active TB on patients’ lung health, a better understanding of the mechanisms involved in the development of PTLD at all stages of TB treatment is needed.
Research Objectives and Scope
The purpose of this NOSI is to invite applications for basic and translational research establishing and utilizing animals to model the development of PTLD. This NOSI supports the establishment and usage of preclinical animal models that strive to better understand the pathophysiology of long-term lung damage resulting from pulmonary TB. Validating results with animal models using clinical samples is allowed, but clinical trials and clinical research will not be supported under this NOSI.
Research Topics of Interest
NIAID is interested in research topics that establish preclinical animal models of PTLD development that could enhance studies such as:
- Lung repair mechanisms during and after TB treatment, including interactions among lung resident and circulating immune cells that contribute to tissue destruction and repair.
- Intrinsic host factors predisposing to the development of or protection against PTLD.
- Mechanisms of resolution of lung tissue damaging inflammatory response, including host immune effector and cell death processes.
- Potential effect of HIV including the impact of CD4+ T cell counts, antiretroviral therapy (ART) status and regimen, and viral suppression.
Extensive studies of the effect of HIV have not been conducted to determine whether ART, the level of viral suppression, or immune reconstitution have roles in PTLD development.
Nonresponsive Areas of Research
Review the list below for research areas that will be considered nonresponsive and will not be reviewed.
- Applications proposing clinical research, or the use of clinical samples outside of validating results from animal models.
- Applications exclusively focusing on modeling established PTLD.
- Applications involving TB reactivation in animal models.
- Applications on therapeutics focused on treatment shortening or improving Mtb killing unrelated to long-term lung health.
Application and Submission Information
This notice applies to due dates on or after February 5, 2025, and subsequent receipt dates through January 7, 2028. Apply for this initiative using one of the following notices of funding opportunities (NOFOs) or any subsequent reissueances of these NOFOs through the expiration date of this NOSI.
- NIH Research Project Grant (Parent R01, Clinical Trial Not Allowed)
- NIH Exploratory/Developmental Research Grant Program (Parent R21, Clinical Research Not Allowed)
You should follow all instructions in the SF 424 (R&R) Application Guide and the NOFO through which you submit. Additionally, you must include “NOT-AI-24-082” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF 424 R&R form to be considered for funding in response to this initiative. NIAID will not consider applications that do not have this information in box 4B.
Contact Information
Direct any inquiries to NIAID’s scientific/research contact, Dr. Robert Mahon at robert.mahon@nih.gov or 240-669-5427.