Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
ABSTRACT Tuberculosis (TB) remains a leading cause of mortality in people living with HIV (PLHIV), with 161,000 deaths in 2023 despite widespread use of combinatorial antiretroviral therapy (cART). Although cART effectively suppresses HIV replication, it does not eliminate the markedly elevated risk of Mycobacterium tuberculosis (Mtb) reactivation in co-infected individuals. This persistent susceptibility is thought to stem from incomplete immune reconstitution, including impaired TH1/TH17 balance, reduced CD4⁺ effector memory T (TEM) cells, and ongoing immune activation in the lung. Our preliminary studies in an established Mtb/SIV rhesus macaque model demonstrate that cART alone fails to restore IL-21 and STAT1 signaling, both critical for immune control of TB and HIV. IL-21, a pleiotropic cytokine produced by CD4⁺ T cells, regulates TH1 and TH17 responses and supports macrophage function. Prior work shows that IL-21-IgFc therapy in SIV-infected macaques is safe and preserves mucosal immunity. We propose that IL-21-IgFc, when administered during early cART, can enhance immune reconstitution, reduce viral persistence, and improve TB control. The central hypothesis of this study is that adjunctive IL-21-IgFc therapy will restore key immune pathways in the lung, limit viral reservoirs, and improve macrophage function—thereby preventing Mtb reactivation in SIV- infected macaques. To test this, we will pursue two specific aims: • Aim 1 will determine how IL-21-IgFc therapy during early cART impacts pulmonary immune reconstitution and Mtb-specific responses. We will assess T cell subsets, STAT1/STAT3 signaling, granuloma integrity, and transcriptional signatures using flow cytometry, scRNAseq, and spatial transcriptomics. Additionally, we will perform cross-species transcriptomic comparisons between NHP and human PBMCs from cART-treated and untreated cohorts to identify conserved immune signatures and pathways associated with protection or disease progression. • Aim 2 will evaluate the effect of IL-21-IgFc therapy on viral persistence and macrophage function. We will measure SIV reservoirs in lung tissue, quantify macrophage proliferation, and assess tissue pathology to determine the impact of IL-21 on HIV-associated innate immune dysfunction. Impact: These studies will elucidate mechanisms by which IL-21 enhances lung immunity and limits pathogen persistence in TB/HIV co-infection. Findings will guide development of IL-21-based immunotherapies, a promising host-directed strategy to improve outcomes in high-burden populations where TB and HIV remain syndemic.
Grant Summary
Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $927K for university, nonprofit, healthcare org. Applications are due 2031-04-30 (open). Check eligibility and apply with FindGrants.
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Up to $927K
2031-04-30
- 1Confirm your organization is eligible for Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection 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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Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection: Frequently Asked Questions
Who is eligible for the Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection?
Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection 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 Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection provide?
Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection provides up to $927K 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 Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection deadline?
Applications for Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection are due 2031-04-30 (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 Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection?
To apply for Enhancing pulmonary immune reconstitution and limiting viral persistence with IL-21 therapy in Mtb/SIV co-infection, 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.