Understanding Mechanisms and Outcomes of Trained Immunity (R01 Clinical Trial Not Allowed) | PAR 24 112

Opportunity Information: Apply for PAR 24 112

This funding opportunity, titled "Understanding Mechanisms and Outcomes of Trained Immunity (R01 Clinical Trial Not Allowed)" (PAR-24-112), is a discretionary National Institutes of Health (NIH) research project grant (R01) focused on advancing the science of trained immunity, also described as innate immune memory. The core goal is to support studies that explain the basic biological mechanisms that drive trained immunity, identify measurable biomarkers that indicate when and how trained immunity is occurring, and clarify what trained immunity actually does in real immune contexts. A key boundary of this announcement is that it does not allow clinical trials, so the emphasis is on mechanistic, translational, and discovery-oriented research rather than interventional clinical testing.

The NOFO highlights three broad areas where trained immunity is especially relevant and where NIH is seeking deeper understanding. First, it encourages research on how trained immunity shapes immune system development and overall immune function, which can include how early-life exposures, infections, microbiome-related signals, or environmental stimuli influence innate immune programming over time. Second, it supports work examining how trained immunity affects protection against vaccines or natural infections, including why certain exposures might enhance or blunt later immune responses, how innate training interacts with adaptive immunity, and what immune signatures predict better or worse protective outcomes. Third, it welcomes research exploring trained immunity in conditions where immune responses become harmful or misdirected, such as allergic diseases, autoimmune disorders, and rejection of organ, tissue, or cell transplants. In this last category, the focus is on understanding how innate immune memory could contribute to inflammation, tissue damage, graft rejection risk, or disease flares, and how biomarkers might help anticipate these outcomes.

Because the opportunity explicitly calls out mechanisms and biomarkers, strong applications will typically be built around clearly testable hypotheses about underlying biology, such as cellular and molecular pathways, metabolic and epigenetic reprogramming, persistence and durability of trained states, and the identity and behavior of innate immune cells involved (for example, monocytes/macrophages, NK cells, and progenitor or stem-cell-associated contributions). Biomarker-oriented aims could include developing or validating assays and signatures that reflect trained immunity status, magnitude, or functional consequences, with an eye toward reproducibility and usefulness across models or populations. Even though clinical trials are not allowed, studies can still be relevant to human health through observational human immunology, use of human samples, ex vivo functional assays, computational analyses, or preclinical and mechanistic model systems designed to illuminate human disease and vaccine biology.

Eligibility is broad and includes many types of organizations and institutions. Eligible applicants listed include state, county, city or township governments; 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; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories); for-profit organizations other than small businesses; small businesses; and other organizations as permitted. The NOFO also specifically notes additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), 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, U.S. territories or possessions, and even non-U.S. entities (foreign organizations). This breadth suggests NIH is encouraging wide participation across different research settings, including institutions serving underrepresented populations and organizations outside the United States when scientifically justified.

Administratively, the opportunity is in the health funding activity category and is associated with CFDA number 93.855. It was created on January 25, 2024, and lists an original closing date of January 7, 2027, indicating a multi-year window during which applications may be accepted according to the NOFO schedule. The award ceiling is not specified in the provided source data, and the expected number of awards is also not listed, which typically means applicants should refer to the full NIH announcement and standard R01 budget guidance and institute-specific policies to understand realistic budget expectations and paylines.

In practical terms, this NOFO is aimed at researchers who can connect the emerging concept of trained immunity to clear biological mechanisms and measurable indicators, and then link those findings to meaningful immune outcomes in development, vaccination and infection, and immune-mediated diseases like allergy, autoimmunity, and transplant rejection. It is a good fit for teams combining immunology, systems biology, genomics/epigenomics, metabolism, bioinformatics, and model-based experimentation, especially when the work can produce broadly useful mechanistic insights and biomarker tools that clarify when trained immunity helps and when it harms.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Understanding Mechanisms and Outcomes of Trained Immunity (R01 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.
• 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 24 112

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