Understanding Mechanisms and Outcomes of Trained Immunity (R21 Clinical Trial Not Allowed) | PAR 24 111

Opportunity Information: Apply for PAR 24 111

The NIH funding opportunity PAR-24-111, titled "Understanding Mechanisms and Outcomes of Trained Immunity (R21 Clinical Trial Not Allowed)," supports exploratory, early-stage research aimed at clarifying how trained immunity (also called innate immune memory) is established, maintained, and expressed, and how it ultimately affects health and disease. The main emphasis is on basic biological mechanisms and measurable biomarkers that can reliably indicate trained immune states, along with the real-world functional consequences of those changes. Because this is an R21 mechanism, it is geared toward innovative, high-impact ideas that may be at an earlier stage of development, including projects that generate strong proof-of-concept data, develop new approaches, or open up new lines of investigation rather than large, definitive programs of work. As noted in the title, clinical trials are not allowed under this announcement, so projects need to stay on the mechanistic and preclinical or non-trial human research side (for example, laboratory studies, model systems, or clinical samples used for mechanistic analyses rather than interventional trials).

Scientifically, the NOFO is interested in trained immunity as a form of adaptive behavior within the innate immune system, where prior exposures can leave lasting imprints that shape later responses. The solicitation seeks studies that improve understanding of (1) immune system development and overall immune function, meaning how trained immunity influences maturation and baseline responsiveness of innate immune cells and broader immune networks; (2) immunity to vaccines or natural infections, meaning how trained immune programming might strengthen, weaken, or otherwise alter protection and immune response quality after vaccination or infection; and (3) immune-mediated conditions, including allergic diseases, autoimmunity, and rejection of organ, tissue, or cell transplants, where trained immunity may contribute to inflammation, immune dysregulation, or graft outcomes. Across these themes, the opportunity highlights both mechanisms (the "how" at molecular, cellular, and systems levels) and biomarkers (the "how to measure it" in a way that could be used consistently across studies).

Key administrative features include that it is a discretionary grant program under NIH, categorized in the health funding activity area and associated with CFDA number 93.855. The award ceiling is listed as $275,000. The original closing date provided is January 7, 2027. While the expected number of awards is not specified in the provided source data, applicants should treat this as a competitive research solicitation in which funding levels depend on NIH priorities, available funds, and peer review outcomes.

Eligibility is broad and includes many types of U.S.-based organizations as well as certain international entities. Eligible applicants include state, county, city, township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations that are not federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories); for-profit organizations other than small businesses; and small businesses. The announcement also explicitly calls out additional eligible applicant types and community-anchored institutions, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, tribal governments that are not federally recognized, non-domestic (non-U.S.) entities (foreign organizations), and U.S. territories or possessions. This broad eligibility signals an interest in drawing from diverse research environments and communities, including institutions that serve populations historically underrepresented in biomedical research.

In practical terms, a strong application under this NOFO would typically propose a clear, testable set of mechanistic questions about how innate immune cells (and related tissue environments) acquire memory-like features after specific exposures, identify or validate biomarkers that reflect those trained states, and connect those biomarkers to meaningful functional outcomes tied to immune development, vaccine/infection responses, or immune-mediated diseases such as allergy, autoimmunity, and transplant rejection. The "clinical trial not allowed" restriction is an important boundary condition: applicants can often use human specimens, observational cohorts, and ex vivo or in vitro functional testing, but should avoid proposing interventional studies that meet the NIH definition of a clinical trial.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Understanding Mechanisms and Outcomes of Trained Immunity (R21 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2024-01-25.
• Applicants must submit their applications by 2027-01-07.
• Each selected applicant is eligible to receive up to $275,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 24 111

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