The Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP) supports research in preclinical nonhuman primate (NHP) and human decedent models of porcine pancreatic islet, kidney, heart, lung, or liver xenotransplantation. IXCRP’s overarching goal is to develop safe and effective strategies to enable clinical xenotransplantation.
Through two reissued notices of funding opportunities (NOFOs), you can apply to join the IXCRP consortium:
- Immunobiology of Xenotransplantation (U01, Clinical Trial Not Allowed)
- Immunobiology of Xenotransplantation (U19, Clinical Trial Not Allowed)
The two NOFOs share overlapping research objectives and priority topics, although the U01 NOFO is meant to invite single research project applications while the U19 NOFO is appropriate for applications proposing complex research programs involving two or more research projects.
Research Objectives
The NOFOs identify several major immunologic and physiologic barriers to achieving safe and efficacious xenotransplantation, and specify that research projects should focus on:
- Developing or optimizing models, including genetic modifications of the pig-donor to address FDA concerns and refinement of surgical xenotransplantation techniques.
- Developing or optimizing immunosuppression regimen to prevent rejection and minimize toxicity.
- Characterizing and resolving physiological and immunological barriers to long-term xenograft survival.
- Developing or optimizing strategies to screen for and prevent pathogen transmission to recipients.
Examples of fitting research topics include:
- Elucidating the cellular and molecular mechanisms of and development of strategies to prevent hyperacute, acute, and chronic xenograft rejection.
- Developing approaches to eliminate or minimize the use of immunosuppressive drugs through genetic modifications of donor organs, tissues, or cells, utilizing encapsulation techniques, or other tolerogenic approaches.
- Characterizing approaches to address differences in the anatomical, physiological, or endocrinological features of donor pig organs, tissues, or cells that limit a xenograft’s survival and function in NHP or human decedent recipients.
The NOFOs offer a much longer list of possible research topics that meet the goals of this initiative.
They also stipulate types of applications that NIAID will consider nonresponsive and not review, such as:
- Pig-to-NHP xenotransplantation studies of any organs, tissues, or cells other than pancreatic islets, kidney, heart, lung, or liver.
- Small animal models of xenotransplantation, such as rodent models, unless the model is proposed only as an in vivo bioassay of large animal immune function.
- Studies of zoonotic agents or infections, except for those studies designed to prevent transmission of, or improve diagnosis, monitoring, or treatment of zoonotic infections in xenograft recipients.
Again, refer to NOFOs for complete details.
Both U01 and U19 applications must propose explicit, detailed, and quantitative annual milestones. NIAID program staff will use the milestones to assess annual progress and support funding decisions.
Further, U19 applications must propose an administrative core, optional scientific cores, and at least two synergistic research projects.
Recipient principal investigators (PIs) funded through this initiative will form a Steering Committee after awards are made. The Steering Committee will serve as the main governing body of IXCRP.
Application Requirements
Through this initiative, NIAID aims to fund three to five awards.
For both NOFOs, the project period is capped at 5 years and must reflect the scope of the proposed project.
U01 application budgets are not limited but, as a rough guideline, should total between $700,000 to $800,000 in annual direct costs. Likewise, U19 application budgets are not limited but should amount to about $1.3 million annual direct costs. In either case, your budget must reflect the actual needs of the proposed project.
Act quickly! The NOFOs have a single application due date on August 9, 2024, at 5 p.m. local time of the applicant organization.
Direct questions about the initiative to Dr. Nasrin Nabavi at nnabavi@niaid.nih.gov or 240-627-3538. For matters specific to peer review, reach out to Dr. James Snyder at james.snyder@nih.gov or 240-669-5060.