Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R21) | PA 16 373

Opportunity Information: Apply for PA 16 373

The National Institutes of Health (NIH) grant opportunity "Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R21)" (Funding Opportunity Number PA-16-373) is designed to fund early-stage, high-impact research projects that push new ideas forward in the field of primary immunodeficiency diseases (PIDs). Using the NIH R21 mechanism, the program emphasizes exploratory and developmental work, meaning it is geared toward innovative concepts, proof-of-principle studies, and the generation of preliminary data that could later support larger, more definitive projects. The overall focus is on improving how PIDs are detected and understood at the molecular level, and on advancing novel therapeutic approaches.

A central theme of the announcement is support for studies that use human biological materials in ex vivo settings, such as experiments conducted on patient-derived blood cells, tissues, or other clinical specimens outside the body. This includes research aimed at understanding immune dysfunction in real patient samples, identifying disease mechanisms, and evaluating potential interventions using patient material in a controlled laboratory context. Alongside human specimen work, the FOA also strongly supports studies using animal models, whether established models already used in PID research or newly developed models that better reflect human disease. The intention is to stimulate work that refines or creates models that can reveal disease pathways, validate candidate genes or variants, and serve as platforms for testing emerging therapeutic strategies.

The FOA also explicitly welcomes projects that propose novel clinical strategies connected to PIDs. These strategies can include improved approaches for detecting and diagnosing immunodeficiencies, methods to identify the underlying molecular basis of disease (for example, linking genetic changes to immune phenotypes), and innovative therapy development. While the announcement is not limited to any single methodology, it is clearly oriented toward creativity and translational potential, encouraging projects that can move the field toward better clinical recognition of PIDs and more targeted, mechanism-informed treatments.

Another major emphasis is the use of existing clinical resources, particularly data and biospecimens housed in PID registries, consortium databases, and repositories. The FOA aims to increase the value extracted from these established infrastructure investments by encouraging investigators to analyze clinical datasets and associated samples to answer important research questions in PID biology and patient care. In practice, this can include genotype-phenotype analyses, outcome studies, biomarker discovery, identification of disease subtypes, and other integrative analyses that are difficult to accomplish without access to large, well-curated patient cohorts and shared repositories.

In terms of administrative details, this is a discretionary NIH grant opportunity within the health funding category, associated with CFDA numbers 93.855 and 93.856. The listed award ceiling is $200,000, reflecting the smaller, exploratory nature typical of the R21 mechanism. The opportunity was created on July 19, 2016, and the original closing date shown is July 16, 2017, indicating it was posted for a defined application window at that time.

Eligibility is broad and includes many types of domestic organizations and governmental entities. Eligible applicants include state, county, city or 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; and tribal organizations that are not federally recognized. It also includes public housing authorities/Indian housing authorities, nonprofits with and without 501(c)(3) status (excluding higher education institutions in those nonprofit categories), for-profit organizations other than small businesses, and small businesses. The announcement also calls out additional eligible applicant categories such as 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, regional organizations, eligible federal government agencies, and U.S. territories or possessions.

At the same time, the FOA draws clear boundaries around foreign participation. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply as applicant organizations, and non-domestic components of U.S. organizations are also not eligible to apply. However, foreign components are allowed under NIH policy as defined in the NIH Grants Policy Statement, meaning a U.S.-based applicant may include certain foreign collaborations or activities if they meet NIH requirements and are appropriately justified. This structure preserves U.S. applicant eligibility while still allowing limited international elements when they add scientific value.

Overall, this FOA is aimed at sparking fresh, testable ideas in primary immunodeficiency research by funding projects that rely on patient specimens, animal model development or use, innovative diagnostic and mechanistic strategies, and strong use of existing registry and repository resources. The intent is to accelerate discovery and early translational steps in a field where understanding disease mechanisms and improving clinical management can directly change outcomes for patients with inherited immune system disorders.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R21)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855, 93.856.
• This funding opportunity was created on 2016-07-19.
• Applicants must submit their applications by 2017-07-16. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $200,000.00 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.

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