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Exploiting Natural Killer cells in HIV/HBV co-infection to achieve eradication

Award Number: R01AI155182
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: 07/09/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Exploiting Natural Killer cells in HIV/HBV co-infection to achieve eradication - Exploiting adaptive NK cells in HIV/HBV co-infection towards eradication Project Summary/Abstract Despite the benefits of combined antiretroviral treatment (ART) with dual activity against HIV and HBV, the differences in outcome between HIV/HBV co-infected and HBV mono-infected populations still persist. Our current understanding of the degree of immunological recovery with therapy in these two groups, in particular in terms of hepatic immune responses is scarce, identifying a significant knowledge gap and a barrier to the development of effective functional cures. Recent technical advances, including the use of single-cell RNA sequencing (scRNA- seq) and high-throughput single cell analysis along with fine needle aspirates (FNAs) of the liver from appropriately matched clinical cohorts provide new exciting opportunities to probe hepatic versus peripheral immune signatures. These innovative approaches will be applied to ascertain the transcriptional landscape, proteomic and functional features of immune cell populations in the liver and peripheral blood between HIV/HBV co-infected versus HBV mono- infected patients at an entirely new level of resolution. Particular emphasis will be placed on Natural Killer (NK) cells with adaptive properties and unique subpopulations of NK cells with ‘memory’ features enriched in the liver. These specialised subpopulations that arise in response to chronic viral infections and following vaccination with HIV-encoded envelope protein and endowed with enhanced functionality hold tremendous potential for effective control of virus replication. Therefore, clinical exploitation of adaptive NK cells represents a transformative approach to augment therapy of chronic viral infection. We aim to develop a robust and scalable platform for the expansion of adaptive NK cells with enhanced functionality and predictable selectivity that could circumvent many of the limitations inherent to the various immunotherapeutic approaches tested so far, representing a novel avenue for new or complementary curative strategies.


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: 2024 ( Subtotal = $327,448 )
2024	2024	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Allergy and Infectious Diseases Research	000	5	6/13/2024	NON-COMPETING CONTINUATION	$327,448
														Subtotal = $327,448

Issue Date FY: 2023 ( Subtotal = $335,613 )
2023	2023	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Allergy and Infectious Diseases Research	000	4	6/16/2023	NON-COMPETING CONTINUATION	$335,613
														Subtotal = $335,613

Issue Date FY: 2022 ( Subtotal = $342,227 )
2022	2022	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Allergy and Infectious Diseases Research	002	3	6/17/2022	NON-COMPETING CONTINUATION	$342,227
2022	2021	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Allergy and Infectious Diseases Research	001	2	3/11/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$145,467
2022	2020	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE			GBR	Allergy and Infectious Diseases Research	000	1	3/11/2022	NEW	-$145,467
														Subtotal = $342,227

Issue Date FY: 2021 ( Subtotal = $450,259 )
2021	2021	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Allergy and Infectious Diseases Research	001	2	7/7/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$450,259
2021	2020	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE			GBR	Allergy and Infectious Diseases Research	000	1	7/6/2021	NEW	$0
														Subtotal = $450,259

Issue Date FY: 2020 ( Subtotal = $476,070 )
2020	2020	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD	OXFORDSHIRE	OX1 2JD		GBR	Allergy and Infectious Diseases Research	000	1	7/9/2020	NEW	$476,070
														Subtotal = $476,070

Grand Total All Awards = $1,931,617

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Exploiting Natural Killer cells in HIV/HBV co-infection to achieve eradication

Award Number: R01AI155182

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: 07/09/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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