Synergizing therapeutic vaccination and EZH2 inhibition to enhance CD8 T cell-mediated HIV reservoir clearance
Active Project Grant Awarded Last action
- Award ID
- F31AI203603
- Recipient
-
Weill Medical College Of Cornell University UEI YNT8TCJH8FQ8
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $50,114
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 0% complete
- Place of performance
- New York, NY 10065, USA
Award details come from USAspending.gov.
Description
- Abstract
- HIV infection remains a major global health burden, with nearly 40 million people affected worldwide. Although antiretroviral therapy (art) effectively suppresses viral replication, IT does not eliminate the long-lived reservoir of infected cells capable of reigniting infection. Achieving durable art-free remission will require strategies that both reduce reservoir persistence and enhance HIV-specific CD8 T cell immunity. In chronic infection, HIV- specific CD8 T cells exhibit reduced proliferative capacity, impaired cytotoxicity, and limited efficacy following therapeutic vaccination. My prior work identified enhancer of zeste homolog 2 (EZH2) as a key epigenetic barrier that supports reservoir persistence. Clinically validated EZH2 inhibitors increase the immunogenicity of infected cells and promote stem-like states in CD8 T cells, positioning them as promising immune-enhancing agents. However, the CD8 T cell-intrinsic effects of EZH2 inhibition remain incompletely defined, and IT is unknown whether these changes improve the efficacy of therapeutic vaccination. I hypothesize that EZH2 inhibition intrinsically reprograms HIV-specific CD8 T cells toward TCF-1+ tscm phenotypes and that therapeutic vaccination can leverage this reprogramming to promote durable viral control. This proposal will mechanistically define the phenotypic, functional and epigenetic effects of EZH2 inhibition on HIV-specific CD8 T cell responses following antigenic stimulation and therapeutic vaccination. IT will also determine whether EZH2- mediated immune modulation enhances antiviral activity and delays viral rebound. By identifying epigenetic mechanisms that potentiate vaccine-driven CD8 T cell responses, this work aims to establish a rational strategy for integrating EZH2 inhibition in HIV cure approaches capable of achieving durable reservoir control.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $0 | |
| Original award | $50,114 |
Quick answers
Who received award F31AI203603?
F31AI203603 was awarded to Weill Medical College Of Cornell University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on February 21, 2027.
How much is award F31AI203603 worth?
$50,114 has been obligated on F31AI203603.
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