The National Institute of Allergy and Infectious Diseases (NIAID) is soliciting applications under the R21 Exploratory/Developmental Research Grant mechanism for research aimed at improving the understanding of trained immunity, also known as innate immune memory. This funding opportunity focuses on uncovering the basic mechanisms, biomarkers, and functional implications of trained immunity in contexts such as immune system development and function, immunity to vaccines or natural infections, and immune-mediated diseases like allergies, autoimmunity, and organ/tissue transplant rejection. The grant supports shorter-term exploratory studies that contribute to foundational knowledge in this emerging field, particularly in identifying molecular and cellular mechanisms, characterizing immune responses, and exploring the duration and plasticity of trained immunity effects.

Research priorities include identifying novel biomarkers associated with trained immunity, studying its role in immune-mediated diseases, elucidating the mechanisms underlying innate immune memory, and determining how trained immunity influences adaptive immune responses and disease outcomes. Descriptive studies aiming to define immune signatures and phenotypes associated with trained immunity are allowed. However, applications focusing solely on antigen-specific adaptive immunity, studies without mechanistic or biomarker exploration, research conducted exclusively in non-mammalian systems without translational relevance, HIV/AIDS-related studies, or proposals involving clinical trials will not be considered responsive.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, local and state governments, tribal entities, independent school districts, public housing authorities, regional organizations, and foreign entities. Institutions serving underrepresented communities, such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, and Tribal Colleges and Universities (TCCUs), are encouraged to apply. Applicant organizations must complete registrations with SAM, NATO Commercial and Government Entity (NCAGE) Code (for foreign applicants), Grants.gov, and eRA Commons before submission. Principal Investigators must have an active eRA Commons account.

The grant provides a total budget of up to $275,000 in direct costs over two years, with no more than $200,000 requested in any single year. The maximum project period is two years. Applications must follow NIH's standard submission procedures, including the preparation of a Data Management and Sharing Plan, adherence to page limits, and compliance with NIH human subjects and animal research policies. Proposals must emphasize the knowledge gaps they aim to address, outline innovative approaches, and include strategies for addressing potential challenges.

Applications will be evaluated based on their scientific merit, including significance, investigator expertise, innovation, approach, and the research environment. The review process will assess the likelihood of the proposed studies to advance the understanding of trained immunity, the robustness of experimental designs, and the feasibility of achieving the project aims within the given timeframe. Additional considerations include human subjects' protections, inclusion of diverse populations, and compliance with NIH data-sharing policies.

The earliest submission date is May 16, 2024, with application deadlines set for June 16 and October 16 annually through October 16, 2026. Applications must be submitted electronically via NIH ASSIST, Grants.gov Workspace, or institutional system-to-system platforms. Prospective applicants are encouraged to submit a letter of intent at least 30 days before the due date and consult with NIAID program officials for guidance. Successful applications are expected to contribute significantly to the foundational understanding of trained immunity, enabling future advances in immunological research and clinical applications.