Enterprise for research and advocacy to stop and eradicate HIV (ERASE-HIV)
Active Cooperative Agreement Awarded Last action
- Award ID
- UM1AI164562
- Recipient
-
Emory University UEI S352L5PJLMP8
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $36,141,119
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 78% complete
- Originally
- Funding
-
- $35,240,203.00 Federal
- $900,916.00 Non-federal
- Funding agency
- National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health, Department of Health and Human Services
- Place of performance
- Atlanta, GA 30329, USA
Award details come from USAspending.gov.
Description
- Abstract
- The presence of a reservoir of cells harbouring integrated, replication-competent virus that persists under long- term, fully suppressive antiretroviral therapy (art) and the inability of the host immune responses to control the initial events of viral replication that follow art interruption are critical barriers to curing HIV infection. Thus, novel therapeutic strategies to remove these barriers are critically needed. The overarching hypotheses of erase HIV are: (I) decreased and/or dysfunctional CD8+ T and NK cell antiviral functions, combined with the recently-described CD8+ T-cell-mediated transcriptional silencing of HIV, favour HIV persistence under art and prevent the control of viremia if art is stopped; and (II) novel approaches to elicit effective CD8+ T-cell, NK cell, and antibody-dependent cellular cytotoxicity (ADCC) functions while inhibiting the CD8+ T-cell-mediated virus silencing will promote remission and/or eradication of HIV. The overarching goal of erase HIV is to identify novel mechanisms of HIV persistence and to test them in the most relevant pre-clinical animal models through mechanistically-oriented, community-supported therapeutic strategies that can be ultimately translated to cure HIV infection in humans. Erase HIV includes three highly integrated research foci (RFS). RF1 is aimed at identifying the molecular and cellular mechanisms underlying the two distinct antiviral activities of CD8+ T-cells: the MHC-restricted, AG-specific response that directly eliminates virus-infected cells, and the non-MHC restricted, non-cytolytic silencing of HIV transcription. As such, RF1 will provide the conceptual basis for the interventions tested in RF2 and RF3. RF2 will use animal models of art-treated HIV infection to (I) restore CD8+ T and NK cell function with a combined a-IL-10 and IL-15 superagonist (N-803) strategy; (II) target rebounding virus by using a CD4-mimetic compound (CD4MC) to enhance antibody recognition of cells expressing HIV ENV and their elimination via ADCC; and (III) determine if improving CD8 T and NK cell function via a-IL-10 and N- 803 synergizes with CD4MC to clear infected cells. RF3 will determine if suppression of the latency-promoting activity of CD8+ T-cells, coupled with N-803 and interventions to promote apoptosis (BCL-2 inhibitors) or immune- mediated removal (CD4MC) of cells that have reactivated virus, will reduce the reservoir size. In all, we will exploit the synergy between the mechanistic data generated in RF1 and the in vivo interventions in RF2 and RF3 to validate a strategy that targets both HIV persistence during art and HIV recrudescence after art interruption. Erase HIV is supported by experts in HIV advocacy (SISTERLOVE); recognition and killing of HIV ENV-expressing cells (FINZI/SODROSKI); T and NK cell biology (SEKALY/RIBEIRO/DELEAGE/PARSONS); reservoir assays and latency models (KULPA/JONES/LITCHTERFELD/HOWELL); pre-clinical animal studies (paiardini/silvestri/garcia/saez- cirion/keele/kumar); mathematical modelling (DAVENPORT); and therapeutics development (merck and immunitybio) for HIV cure. We believe that the proposed mechanistically-oriented pre-clinical work will inform strategies that can be translated in clinical trials to achieve prolonged viral remission in PWH.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | $4,078,260 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $208,333 | $0 | |
| Amendment | $3,997,064 | $0 | |
| Amendment | $166,666 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $125,000 | $0 | |
| Amendment | $125,000 | $0 | |
| Amendment | $910,000 | $0 | |
| Amendment | $910,000 | $0 | |
| Amendment | $910,000 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $4,060,223 | $0 | |
| Amendment | $125,000 | $0 | |
| Amendment | $125,000 | $0 | |
| Amendment | $4,060,223 | $0 | |
| Amendment | $125,000 | $0 | |
| Amendment | $125,000 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $609,250 | $0 | |
| Amendment | $609,250 | $0 | |
| Amendment | $609,250 | $0 | |
| Amendment | $609,250 | $0 | |
| Amendment | $609,250 | $0 | |
| Amendment | $609,250 | $609,250 | |
| Amendment | $609,250 | $0 | |
| Amendment | $166,666 | $0 | |
| Amendment | $4,136,426 | $0 | |
| Amendment | $208,333 | $0 |
Show 40 more
Latest 50 listed here. See the rest on GovTribe.
Subawards
Show all 30
Quick answers
Who received award UM1AI164562?
UM1AI164562 was awarded to Emory University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 16, 2021.
How much is award UM1AI164562 worth?
$36,141,119 has been obligated on UM1AI164562: $35,240,203 in federal funding and $900,916 in non-federal funding.
Which agency awarded UM1AI164562?
National Institute of Allergy and Infectious Diseases (National Institutes of Health) awarded UM1AI164562, with funding from National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health).
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award