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Antigen-specific ‘kick and kill’ of the latent HIV reservoir using dendritic cells

Award Number: R01AI152655
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/05/2021
PERIOD OF PERFORMANCE END DATE: 10/31/2026

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Antigen-specific ‘kick and kill’ of the latent HIV reservoir using dendritic cells - ABSTRACT The persistence of the latent viral reservoir remains a hurdle for the cure of chronic HIV infection. Finding an effective and non-toxic means to purge and expose the viral reservoir has been elusive and is considered a major barrier to the cure. Because of their pivotal role in the initiation and regulation of adaptive T cell immunity, dendritic cells (DC) have been a therapeutic target for both cancer and HIV. Our most recent findings show that with optimal programming, DC have the provocative potential to both drive expansion of HIV-specific cytotoxic T cell lymphocytes (CTL), and to effectively induce HIV latency reversal (LR) to expose the infected cells for CTL targeting and elimination. We have determined that our specialized IL-12p70-producing type-1 polarized monocyte derived DC therapeutic platform (MDC1) can facilitate HIV LR when loaded with either CMV or HIV immunogenic peptides, suggesting that a considerable component of the HIV cellular reservoir is contained among CMV- and HIV specific CD4+ T cells. Here we propose the optimization of MDC1-based immunotherapy strategy that utilizes MHC class II associated CMV epitopes along with highly conserved MHC class I restricted HIV peptides as combined antigenic components designed to facilitate both the exposure of CD4+ T cells harboring latent HIV (the ‘kick’) and their elimination by HIV specific CTL (the ‘kill’). In our proposed studies we will dig deeper into the mechanisms involved, and we will translate our in vitro findings to test this approach in vivo using a humanized mouse model of HIV infection and MDC1 immunotherapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $637,792 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	5	12/10/2025	NON-COMPETING CONTINUATION	$637,792
														Subtotal = $637,792

Issue Date FY: 2025 ( Subtotal = $618,659 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	4	1/6/2025	NON-COMPETING CONTINUATION	$618,659
														Subtotal = $618,659

Issue Date FY: 2024 ( Subtotal = $652,156 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	3	10/23/2023	NON-COMPETING CONTINUATION	$586,941
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	001	3	5/15/2024	NON-COMPETING CONTINUATION	$65,215
														Subtotal = $652,156

Issue Date FY: 2023 ( Subtotal = $634,631 )
2023	2023	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	2	10/25/2022	NON-COMPETING CONTINUATION	$634,631
														Subtotal = $634,631

Issue Date FY: 2022 ( Subtotal = $624,970 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Allergy and Infectious Diseases Research	000	1	11/5/2021	NEW	$624,970
														Subtotal = $624,970

Grand Total All Awards = $3,168,208

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Antigen-specific ‘kick and kill’ of the latent HIV reservoir using dendritic cells

Award Number: R01AI152655

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 11/05/2021

PERIOD OF PERFORMANCE END DATE: 10/31/2026

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