Immunobiology of Xenotransplantation (U01 Clinical Trial Not Allowed) | RFA AI 19 042

Opportunity Information: Apply for RFA AI 19 042

The Immunobiology of Xenotransplantation (U01 Clinical Trial Not Allowed) funding opportunity (RFA-AI-19-042) is a National Institutes of Health (NIH) cooperative agreement solicitation designed to build and strengthen a coordinated research effort in xenotransplantation immunobiology. The program it supports, the Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP), focuses on creating and refining rigorous preclinical models in which organs or tissues from pigs are transplanted into nonhuman primates (NHPs). The emphasis is on generating mechanistic, clinically relevant knowledge that can help move xenotransplantation closer to safe and effective use in humans.

Scientifically, the FOA is centered on porcine-to-NHP models for several high-impact transplant targets: pancreatic islets, kidney, heart, lung, and liver. These models are intended to mimic, as closely as possible, the immune and physiological challenges expected in human xenotransplantation. Projects are expected to probe why xenografts fail, how rejection unfolds over time, and what conditions might allow long-term acceptance. That includes studying both classic rejection pathways and broader inflammatory and innate immune responses that are particularly important in cross-species transplantation.

The goals of the program are laid out in three connected themes. First, applicants are expected to delineate the cellular and molecular mechanisms that drive xenograft rejection and/or enable immune tolerance. In practice, that means identifying which immune cells and pathways are responsible for damage, how antibodies and complement contribute, what role innate immune recognition plays, and what signatures correlate with graft survival versus failure. Second, the FOA seeks development of strategies that improve xenograft survival. This can involve testing immunomodulatory approaches, tolerance-induction concepts, or other interventions that are still preclinical in nature, with outcomes measured in robust NHP xenotransplant models. Third, the FOA highlights physiological compatibility and limitations, recognizing that success is not only about controlling immunity but also about whether the pig graft can meet the recipient's physiological needs over time. Applicants are therefore encouraged to characterize functional performance, species-specific incompatibilities (for example, in coagulation or inflammatory cascades), and practical barriers that could prevent translation.

From a program structure standpoint, this is a U01 cooperative agreement rather than a standard research grant, which means NIH anticipates substantial involvement and collaboration between awardees and the funding institute during the conduct of the work. The cooperative research framing signals an organized, team-science approach where projects are expected to contribute to shared program goals, adopt strong preclinical rigor, and generate findings that collectively accelerate progress toward clinical strategies. Even though the long-term objective is clinical application, this particular FOA explicitly does not allow clinical trials, keeping the research firmly in the preclinical and mechanistic domain.

Eligibility is broad across U.S.-based organizations and includes many types of domestic institutions and entities: state, county, and local 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 and Indian housing authorities; nonprofits with and without 501(c)(3) status (outside of higher education); for-profit organizations other than small businesses; and small businesses. The FOA also calls out a range of additional eligible applicant categories that NIH often encourages, including Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), as well as faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

At the same time, the opportunity draws a clear boundary around foreign participation. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components as defined by the NIH Grants Policy Statement are not allowed. In other words, applications must be fully domestic in both the applicant organization and the performing components covered by the award.

Administratively, the opportunity is listed under the health activity category and references CFDA number 93.855. The original closing date provided for submission was 2019-09-16, and the opportunity record indicates an award ceiling was not specified in the provided summary data. Overall, the FOA is best understood as a targeted NIH effort to fund coordinated, high-quality preclinical xenotransplantation research that explains mechanisms of rejection and tolerance, tests survival-improving strategies, and addresses cross-species functional compatibility, with the explicit intention of laying a credible scientific foundation for eventual clinical translation.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Immunobiology of Xenotransplantation (U01 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 2019-05-30.
• Applicants must submit their applications by 2019-09-16. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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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