A Multifunctional Biologic to Regulate Transplant Rejection
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
Project Summary/Abstract Solid organ transplantation remains the definitive treatment for end-stage organ failure, but is limited by the adverse effects of lifelong immunosuppression and the risk of chronic rejection. Blockade of the CD154/CD40 costimulatory pathway has shown unparalleled efficacy in preclinical models, but clinical translation has been hampered by complications and the need for complex multi-component interventions to achieve maximal efficacy. Separately, regulatory T cell (Treg) therapies offer promise but face challenges including high costs, complexity, and concerns about durability in inflammatory environments. This exploratory proposal addresses these limitations through an innovative high-risk, high-reward approach that integrates these two therapeutic strategies into a single recombinant biologic: β-Tol, a multifunctional fusion protein combining anti-CD154 and one or more immunomodulatory moieties. The central HYPOTHESIS is that this novel fusion protein will synergistically inhibit pathogenic effector T cell differentiation, while promoting their conversion into protective Treg. Preliminary data demonstrate that CD154 blockade synergizes with the immunomodulatory moiety to dramatically enhance mouse Treg conversion, while suppressing effector differentiation, and that initial β-Tol constructs outperform conventional anti-CD154 treatment for Treg induction in vitro. The research design employs a multidisciplinary approach combining protein engineering, immunological characterization, and preclinical validation. Specific Aim 1 will define the regulatory identity of Treg induced by different β-Tol candidates using profiling and functional suppression assays to identify optimal construct architecture. Specific Aim 2 will assess therapeutic potential using stringent mouse skin transplant models combined with fate-tracking of alloreactive T cells. Pharmacokinetic studies will inform dosing strategies, while pathological examination will assess safety profiles. By leveraging modular protein engineering and interdisciplinary collaboration, this exploratory proposal seeks to develop a next-generation immunotherapeutic platform for transplantation. Success would provide foundational proof-of-concept for a clinically translatable strategy to induce immune regulation with precision, reduced toxicity, and in the form of a streamlined monotherapy – all aligned with NIH's mission to improve health through innovative biomedical research.
Grant Summary
A Multifunctional Biologic to Regulate Transplant Rejection is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $255K for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
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Focus Areas
Eligibility
How to Apply
Up to $255K
2028-04-30
- 1Confirm your organization is eligible for A Multifunctional Biologic to Regulate Transplant Rejection from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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A Multifunctional Biologic to Regulate Transplant Rejection: Frequently Asked Questions
Who is eligible for the A Multifunctional Biologic to Regulate Transplant Rejection?
A Multifunctional Biologic to Regulate Transplant Rejection is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the A Multifunctional Biologic to Regulate Transplant Rejection provide?
A Multifunctional Biologic to Regulate Transplant Rejection provides up to $255K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the A Multifunctional Biologic to Regulate Transplant Rejection deadline?
Applications for A Multifunctional Biologic to Regulate Transplant Rejection are due 2028-04-30 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the A Multifunctional Biologic to Regulate Transplant Rejection?
To apply for A Multifunctional Biologic to Regulate Transplant Rejection, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.