Tuberculosis Research Units (P01 Clinical Trial Optional)

The Department of Health and Human Services, through the National Institutes of Health and its National Institute of Allergy and Infectious Diseases (NIAID), has released a Notice of Funding Opportunity (NOFO) titled Tuberculosis Research Units (P01 Clinical Trial Optional), under Funding Opportunity Number RFA-AI-25-027. This is a reissue of RFA-AI-20-020. The program aims to establish multidisciplinary Tuberculosis Research Units (TBRUs) as a collaborative network to advance understanding of Mycobacterium tuberculosis (Mtb) and host interactions, specifically focusing on bacterial and host heterogeneity and its role in infection outcomes and disease progression. The NOFO responds to the urgent global and domestic challenges of tuberculosis (TB), which remains the leading cause of death from an infectious disease worldwide, accounting for 1.25 million deaths in 2023. In the United States, TB incidence rose to its highest level in a decade, with approximately 9,600 reported cases in 2023, including pediatric cases. An estimated 13 million Americans live with latent TB, posing a significant risk of disease activation due to comorbidities, malnutrition, and immunosuppression. The persistence of multidrug-resistant strains and the synergistic effect of HIV on TB progression underscore the need for sustained investments in TB research. The TBRU program supports integrated research approaches that combine basic, preclinical, and clinical studies. Each funded TBRU must include at least two interdependent research projects, with one involving animal studies and another involving clinical studies, to ensure translation between laboratory and clinical findings. Administrative and Scientific Cores must provide coordination, management, and technical support. The scope of supported research includes the pathophysiology of subclinical TB, host-pathogen interactions, Mtb persistence and resistance, animal models that replicate human pathogenesis, the role of comorbidities and coinfections, and development of tools for TB research. Applications focusing on vaccine immune correlates, substance abuse, epidemiologic studies, or behavioral research will not be considered responsive. NIAID intends to commit $10 million in FY 2026 to fund 4–5 awards, with individual awards not expected to exceed $1.5 million in direct costs annually. The maximum project period is five years. Applications may propose clinical trials, but these are optional. All applicants must comply with NIH Grants Policy Statement requirements, including Data Management and Sharing Plans, and follow the multi-project application structure as outlined in the Application Guide. Pre-award costs are allowable as described in NIH policy. Eligibility is broad and includes higher education institutions (public, state-controlled, and private), nonprofits, for-profit organizations, local governments, state and tribal governments, federal agencies, independent school districts, public housing authorities, regional organizations, faith-based and community-based organizations, and foreign organizations. However, effective May 1, 2025, NIH will not issue awards involving foreign subawards or subcontracts. Foreign entities may still apply directly or participate as unfunded collaborators, but monetary foreign subawards are prohibited. Required registrations include SAM.gov, NCAGE (for foreign entities), UEI, eRA Commons, and Grants.gov. The earliest submission date is October 7, 2025, with full applications due November 7, 2025, by 5:00 PM local time. Letters of Intent are requested 30 days prior to the application due date. Peer review is scheduled for March 2026, advisory council review in May 2026, and the earliest possible award start date is July 2026. The NOFO will expire on November 8, 2025. Applications must be submitted electronically through NIH ASSIST or institutional system-to-system solutions. Applications that are incomplete, noncompliant, or nonresponsive will not be reviewed. Applicants will be evaluated on significance, investigators, innovation, approach, and environment, with special emphasis on synergy across projects and cores. Applications are reviewed through the NIH peer review process and must adhere strictly to NIH guidance for multi-component applications. Additional review considerations include protections for human subjects, inclusion policies, vertebrate animal use, data management, and compliance with biosafety and biosecurity requirements. Contacts for program-specific inquiries include Richard T. Robinson, Ph.D., at NIAID for scientific questions, and Yescenia Mendoza at NIAID for financial and grants management inquiries.