Understanding Mechanisms and Outcomes of Trained Immunity (R21 Clinical Trial Not Allowed)

The funding opportunity titled “Understanding Mechanisms and Outcomes of Trained Immunity (R21 Clinical Trial Not Allowed)” is offered through the Department of Health and Human Services, administered by the National Institutes of Health (NIH), with the National Institute of Allergy and Infectious Diseases (NIAID) as the primary component. This Notice of Funding Opportunity (NOFO) aims to advance basic research on the mechanisms, biomarkers, and outcomes associated with trained immunity—an emerging concept in immunology that involves a form of innate immune memory not traditionally attributed to adaptive immunity. The term trained immunity refers to the epigenetic and metabolic reprogramming of innate immune cells following exposure to microbial agents or vaccines, which leads to altered immune responses upon subsequent challenges. The NOFO supports exploratory and developmental research to elucidate how trained immunity operates, how it impacts immune system development and function, and its implications for infectious diseases, vaccine responses, and immune-mediated conditions such as allergy, autoimmunity, and transplant rejection. High-priority topics include identifying novel biomarkers, characterizing molecular and cellular mechanisms, assessing functional impacts, and exploring the duration and adaptability of trained immunity responses. Applications should clearly demonstrate how the proposed research will fill critical gaps in knowledge and offer innovative approaches or perspectives. Eligible applicants include a wide range of entities such as higher education institutions (public and private), nonprofits (with or without 501(c)(3) status), for-profit organizations (small and large), and various governmental bodies (local, state, and tribal), as well as foreign institutions and organizations. Individuals with appropriate expertise are encouraged to apply as Program Directors/Principal Investigators (PDs/PIs), and institutions may submit multiple distinct applications. Applicants are required to comply with all necessary registrations including SAM, eRA Commons, Grants.gov, and where applicable, NCAGE codes for foreign entities. Applications must be submitted electronically and comply with all instructions provided in the SF424 (R&R) Application Guide and the NOFO-specific instructions. The earliest application submission date is May 16, 2024, and applications are due on the standard NIH due dates of June 16 and October 16 in 2024, 2025, and 2026, by 5:00 PM local time of the applicant organization. Letters of Intent are due 30 days prior to the application due date. The program does not support clinical trials and explicitly excludes studies that focus solely on adaptive immunity, HIV/AIDS, or non-mammalian models without translational plans. Applications are reviewed using NIH’s rigorous peer review process, with key evaluation criteria including significance, investigator qualifications, innovation, approach, and the environment. Projects are assessed for their potential to contribute significantly to the field of immunology, particularly in advancing the understanding of trained immunity. Successful applicants will receive a Notice of Award and must comply with all NIH grant policies and reporting requirements. The maximum total direct cost is $275,000 for a two-year period, with no more than $200,000 allowed in any single year. Matching is not required. For questions, applicants can contact Dr. Ari Joffe for scientific inquiries and Tamia Powell for grants management.