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NK cell responses to JC polyomavirus

Award Number: R01NS116278
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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NK cell responses to JC polyomavirus - Most healthy individuals are persistently infected with the human polyomavirus JC (JCPyV) without significant consequences, yet in immunocompromised hosts, JCPyV can cause an often fatal disease -- progressive multifocal leukoencephalopathy (PML). There is currently no effective treatment to prevent or treat PML and novel immune-based therapies are urgently needed to decrease the morbidity and mortality associated with PML. Classically, natural killer (NK) cells are viewed as nonspecific effector cells of the innate immune system that play critical roles in defense against viral infections. Unexpectedly, it was recently demonstrated that besides their ability to rapidly eliminate virus-infected cells without the need for prior antigen sensitization, NK cells also exhibit adaptive immune functions. Different forms of adaptive capabilities have been identified among human NK cell subpopulations, including reports of true antigen-specific memory NK cells as well as adaptive NK cells with enhanced antibody-dependent functions. Adaptive NK cell subsets are endowed with potent anti-viral properties and protection mediated by virus-specific memory NK cells has been demonstrated in mouse models. Importantly, increasing evidence suggest that NK cell can mediate anti-viral responses to JCPyV. In particular, our preliminary data now show potent responses to JCPyV peptides by NK cells, isolation and cloning of single JCPyV-specific NK cells, and reduced JCPyV-specific antibody-dependent cellular cytotoxicity in PML patients. Based on these data, we hypothesize that NK cells and antibodies eliciting NK cell responses play a role in JCPyV pathogenesis. Specifically, we propose to build on our preliminary data to investigate the overarching hypothesis that specific subsets of NK cells can mediate potent anti-viral responses against JCPyV and protect immunocompromised patients against PML, through two focused independent Aims: (i) Define mechanisms crucial to control of JCPyV by NK cells; and (ii) Evaluate the role played by JCPyV-specific antibodies in modulating NK cell activity against JCPyV. If successful, the results of these innovative studies will contribute new knowledge of human immune response against JCPyV and provide the rationale to develop novel immunotherapeutic approaches to harness NK cell function against JCPyV.


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 = $282,538 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	5	8/16/2024	NON-COMPETING CONTINUATION	$282,538
2024	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	6/14/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	11/1/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$326,924
2024	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/1/2023	NON-COMPETING CONTINUATION	-$326,924
														Subtotal = $282,538

Issue Date FY: 2023 ( Subtotal = $305,151 )
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	4	9/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$305,151
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	7/14/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$305,151
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	9/21/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$305,151
2023	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $305,151

Issue Date FY: 2022 ( Subtotal = $411,250 )
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	8/11/2022	NON-COMPETING CONTINUATION	$411,250
2022	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/2/2022	NON-COMPETING CONTINUATION	$0
2022	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	2/11/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $411,250

Issue Date FY: 2021 ( Subtotal = $411,250 )
2021	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/14/2021	NON-COMPETING CONTINUATION	$411,250
														Subtotal = $411,250

Issue Date FY: 2020 ( Subtotal = $411,250 )
2020	2020	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/13/2020	NEW	$411,250
														Subtotal = $411,250

Grand Total All Awards = $1,821,439

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NK cell responses to JC polyomavirus

Award Number: R01NS116278

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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