Enhancing susceptibility of HIV reservoirs to CTL through a discovery to translational approach

Active Project Grant Awarded Last action

Award ID
R01AI176601
Recipient
Awarding agency
Obligated
$6,584,438

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 73% complete
Place of performance
New York, NY 10065, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Although modern antiretroviral (ARV) therapies have dramatically improved the outlooks for people living with HIV, they are unable to cure infection. For people with HIV a cure would represent freedom from many burdens, including stigma, expensive medications, and inflammation-associated CO-morbidities. A cure would also have public health benefits, comprising a powerful tool to help end the HIV epidemic. Developing a cure for HIV requires developing an understanding of how the virus persists for years and decades in people, even when new rounds of cellular infection (replication) are blocked by arvs, and despite the ongoing presence of antiviral immune responses. The dominant paradigm has been that the virus hides in a latent state in infected cells and is thus invisible to immune responses. Efforts to cure infection have therefore focused on therapeutically reversing HIV latency to expose these cells to elimination but have thus far yielded disappointing results. This, along with several converging lines of evidence, have led to more recent hypothesis that hiding from the immune system may not be the only mechanism by which HIV persists - but rather that these rare populations of infected cells may have been selected for those that possess cell-intrinsic resistance to killing by cytotoxic t-lymphocytes, even when they express antigen and are seen. This parallels recent findings from immunooncology where IT has now been well established that some immunogenic tumors undergo selection for cell-intrinsic resistance to CTL. For this project, we have assembled a team comprising a pioneer in establishing mechanisms of CTL resistance in tumors, and two HIV experts who have advanced the idea of CTL resistance in this setting through a series of EX vivo studies. By merging these areas of expertise, we aim to comprehensively describe mechanisms of CTL resistance in HIV-infected primary CD4+ t-cells and to discern which of these are at play in real HIV reservoir cells from people with HIV. We will build from these results to select therapeutic targets and identify combination approaches that integrate these with HIV-specific CTL and latency reversal strategies to achieve specific elimination of HIV reservoir-harboring cells EX vivo. We will also leverage an innovative mouse model to test whether engaging these therapeutic targets limits the seeding of HIV reservoirs in vivo. The results of this project are thus expected to be: i) laying a broad foundation for understanding CTL resistance in the HIV reservoir and II) pre-clinical validation of multiple therapeutic targets with the potential to contribute to a cure for HIV.

Transactions

Action Obligated Date
Amendment $827,957
Amendment $770,236
Amendment $82,747
Amendment $82,747
Amendment $744,710
Amendment $744,710
Amendment $744,710
Amendment $862,207
Amendment $862,207
Original award $862,207

Subawards

Subrecipient Amount Awarded
New York Genome Center, Inc. Dr. Sanjana and his lab will lead the CRISPR screens proposed in Aim 1a – working closely with the Jones lab. Specifically, the Sanjana lab will… $1,339,470
Yale Univ In this R01 proposal “Enhancing Susceptibility of HIV Reservoirs to CTL Through a Discovery to Translational Approach� led by Dr. Brad Jones and… $286,975

Quick answers

Who received award R01AI176601?

R01AI176601 was awarded to Weill Medical College Of Cornell University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on March 24, 2023.

How much is award R01AI176601 worth?

$6,584,438 has been obligated on R01AI176601.

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