Harnessing lysosome trafficking for enhanced antigen presentation
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
Project Summary Robust antigen-specific CD4⁺ T cell responses are critical for effective immunity against cancer and infection. Despite advances in adjuvant development and cytokine modulation, strategies to optimize antigen delivery for MHC-II presentation remain underdeveloped. This proposal introduces a modular platform for antigen engineering—termed LyGens (lysosome-targeting antigens)—that leverages natural and de novo designed ligands for lysosomal trafficking receptors (LTRs), with the goal of enhancing lysosomal delivery and antigen presentation. Aim 1 prototypes LyGens that fuse microbial antigens to ligands of two well-characterized LTRs: insulin-like growth factor 2 (IGF2) for the mannose-6-phosphate receptor (M6PR) and transferrin receptor binding peptide (TfRBP) for the transferrin receptor (TfR). Using antigens from Listeria monocytogenes and Mycobacterium tuberculosis, we will test if fusion constructs enhance co- localization with lysosomes and increase peptide-MHC-II complex formation, as measured by immunofluorescence, T cell reporter assays, and targeted immunopeptidomics (SureQuant). Aim 2 addresses the potential signaling concerns of natural ligand use by engineering LyGens fused to EndoTags—de novo designed LTR binders that target M6PR and TfR at sites orthogonal to native ligand binding domains. These EndoTag-LyGens are evaluated for their trafficking efficiency, MHC-II presentation, and signaling bioorthogonality using phospho-protein profiling and IGF2 competition assays. Together, these studies establish the design rules for a new class of engineered antigens that efficiently harness natural intracellular trafficking pathways to potentiate CD4⁺ T cell responses. The platform's modularity, translational potential, and compatibility with existing vaccine technologies suggest broad applicability to cancer, infectious disease, and autoimmunity. Ultimately, this work lays the foundation for programmable antigen delivery systems that can be tailored to elicit precise immunologic outcomes.
Grant Summary
Harnessing lysosome trafficking for enhanced antigen presentation is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $228K for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $228K
2028-04-30
- 1Confirm your organization is eligible for Harnessing lysosome trafficking for enhanced antigen presentation 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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Harnessing lysosome trafficking for enhanced antigen presentation: Frequently Asked Questions
Who is eligible for the Harnessing lysosome trafficking for enhanced antigen presentation?
Harnessing lysosome trafficking for enhanced antigen presentation 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 Harnessing lysosome trafficking for enhanced antigen presentation provide?
Harnessing lysosome trafficking for enhanced antigen presentation provides up to $228K 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 Harnessing lysosome trafficking for enhanced antigen presentation deadline?
Applications for Harnessing lysosome trafficking for enhanced antigen presentation 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 Harnessing lysosome trafficking for enhanced antigen presentation?
To apply for Harnessing lysosome trafficking for enhanced antigen presentation, 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.