The intent of the Creative and Novel Ideas in HIV Research (CNIHR) program is to attract both international and U.S.-based early stage investigators from outside the field of HIV research to help address key scientific questions in HIV research, including emerging issues of long-term survival with HIV infection, prevention of HIV transmission and research towards a cure.
- Term: Up to 2 years
- Up to $150,000 direct cost per year, (the amount of the award will vary depending on the proposal)
11 Awards
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A Super-agonistic antibody to human IL-21 to boost immunity for HIV cure
A Super-agonistic antibody to human IL-21 to boost immunity for HIV cure
Abstract
We have identified a super-agonist monoclonal antibody (mAb) to human IL-21 (hIL-21) by screening homemade libraries. The mAb (clone 2P2) enhances the hIL-21 bioactivity at a level ~10 fold in vitro. The anti-hIL-21 super-agonist mAb represents a novel class of immunostimulating therapeutics to boost IL-21-mediated immune enhancement to eliminate activated latently infected cells for HIV cure. We hypothesize: 1. The super-agonist mAb 2P2 boosts hIL-21 bioactivity to enhance the cytotoxicity of CD8+ T cells and NK cells to eliminate activated latently infected CD4+ T cells. 2.
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Development of a diagnostic T cell assay to confirm disruption of latent HIV-1 infection
Development of a diagnostic T cell assay to confirm disruption of latent HIV-1 infection
Abstract
Current methodologies to quantify latent HIV-1 infection demand high cell numbers, require repeated leukapheresis of subjects and highly expert molecular biology techniques. For HIV cure regimens to reach the clinic, efficient and high-throughput diagnostic assays will be needed to confirm disruption of latent HIV-1 infection, preferably while patients continue antiretroviral therapy (ART).
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A Super-agonistic antibody to human IL-21 to boost immunity for HIV cure
A Super-agonistic antibody to human IL-21 to boost immunity for HIV cure
Abstract
We have identified a super-agonist monoclonal antibody (mAb) to human IL-21 (hIL-21) by screening homemade libraries. The mAb (clone 2P2) enhances the hIL-21 bioactivity at a level ~10 fold in vitro. The anti-hIL-21 super-agonist mAb represents a novel class of immunostimulating therapeutics to boost IL-21-mediated immune enhancement to eliminate activated latently infected cells for HIV cure. We hypothesize: 1. The super-agonist mAb 2P2 boosts hIL-21 bioactivity to enhance the cytotoxicity of CD8+ T cells and NK cells to eliminate activated latently infected CD4+ T cells. 2.
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Targeting Antiapoptotic Signaling for Eradication of HIV Latent Reservoir
Targeting Antiapoptotic Signaling for Eradication of HIV Latent Reservoir
Abstract
Human immunodeficiency virus (HIV) infection creates a long-lived latent reservoir that is maintained during antiretroviral therapy (ART). With a half-life of approximately ~44 months, these latently-infected CD4 T cells threaten recrudescence even after prolonged treatment and are a major impediment to the eradication of virus reservoirs. Our long-term goals are to discover the mechanisms responsible for conveying the very long half-life of latent CD4 T cells and develop strategies to shorten the half-life to allow their elimination during a relevant time interval.
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Targeting Antiapoptotic Signaling for Eradication of HIV Latent Reservoir
Targeting Antiapoptotic Signaling for Eradication of HIV Latent Reservoir
Abstract
Human immunodeficiency virus (HIV) infection creates a long-lived latent reservoir that is maintained during antiretroviral therapy (ART). With a half-life of approximately ~44 months, these latently-infected CD4 T cells threaten recrudescence even after prolonged treatment and are a major impediment to the eradication of virus reservoirs. Our long-term goals are to discover the mechanisms responsible for conveying the very long half-life of latent CD4 T cells and develop strategies to shorten the half-life to allow their elimination during a relevant time interval.
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Bridges Within the HIV-human Hosthogen Genome
Bridges Within the HIV-human Hosthogen Genome
Abstract
The human genome is not a linear sequence, but rather a contorted knot of chromosomes in the three-dimensional space of the nucleus. The transcription community is now starting to realize that chromosomes do not work in isolation. Interchromosomal associations regulate gene expression. This innovation, however, has not been applied to retroviral infections. We still talk of host and pathogen genomes as if they only interact locally.
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Bridges Within the HIV-human Hosthogen Genome
Bridges Within the HIV-human Hosthogen Genome
Abstract
The human genome is not a linear sequence, but rather a contorted knot of chromosomes in the three-dimensional space of the nucleus. The transcription community is now starting to realize that chromosomes do not work in isolation. Interchromosomal associations regulate gene expression. This innovation, however, has not been applied to retroviral infections. We still talk of host and pathogen genomes as if they only interact locally.
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Targeting Tim-3 for elimination of HIV reservoirs
Targeting Tim-3 for elimination of HIV reservoirs
Abstract
This study is aimed at determining whether targeting a novel immune-inhibitory pathway can deplete latently HIV infected CD4 memory T cells in HIV virally suppressed patients. Although antiretroviral therapy (ART) can suppress HIV replication and significantly improve the long-term health of the patient, it is unable to permanently remove latent reservoirs of virus. Therefore, novel strategies are needed to specifically target and destroy latently infected cells.
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Targeting Tim-3 for elimination of HIV reservoirs
Targeting Tim-3 for elimination of HIV reservoirs
Abstract
This study is aimed at determining whether targeting a novel immune-inhibitory pathway can deplete latently HIV infected CD4 memory T cells in HIV virally suppressed patients. Although antiretroviral therapy (ART) can suppress HIV replication and significantly improve the long-term health of the patient, it is unable to permanently remove latent reservoirs of virus. Therefore, novel strategies are needed to specifically target and destroy latently infected cells.
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Defining and Eliminating the Macrophage Reservoir
Defining and Eliminating the Macrophage Reservoir
Abstract
With 34 million people currently living with HIV, stopping the HIV epidemic remains imperative. Highly active antiretroviral therapy (HAART) limits viral replication, but is not curative. Thus, there is an urgent need to define and eliminate the viral reservoir. While the role of resting memory CD4+ T cells is well established, little is known about other cells as reservoirs. Macrophages are a major target of both HIV and SIV infection.