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Immunoprotective Properties of Tissue-resident Memory T Cells in Mice and Humans within Mucosal Sites

Award Number: R01AI121129
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY This is an emergency competitive revision to our existing R01 AI121129. As part of this parent R01 entitled, “Immunoprotective properties of tissue-resident memory T cells in mice and humans within mucosal sites”, we perform longitudinal sampling of the genital skin and HSV-2 lesions for both viral load as well as cytokine levels. This approach was highlighted in our recent paper in the Journal of Clinical Investigation (Roychoudhury et al, 2020, PMID 32125285), in which we show that T cell-derived proteins including interferon gamma and granzyme B surge concurrently with local viral load. We now propose to use this successful approach to a second infectious disease, SARS-CoV-2. The COVID-19 pandemic is an unprecedented event in modern human history, with morbidity and mortality rates dangerously high in the elderly and those with medical comorbidities. Given the current pandemic status, the most urgent goal is to lower case fatality and hospitalization rates. Front line providers need reliable tests to rapidly triage infected patients according to severity and effective therapies to treat them. There is reason for hope; the mean time between presentation and need for hospitalization is a week for SARS-CoV-2 infected patients, which allows a much longer window to intervene than for influenza infection; clinical trials are already assessing various small molecular agents and neutralizing antibodies. Thus, the goals of this application are to use an existing prospective cohort to assess multiple potential biomarkers of progression to severe disease at initial clinical presentation, identify immunologic variables associated with viral elimination over ensuing weeks, and model the optimal timing, dose and duration of therapeutic interventions to prevent respiratory failure. We will leverage the currently surging local epidemic in Seattle; an IRB-approved protocol which is already enrolling infected outpatient participants; a wide network of referring providers; and our multi-disciplinary team of clinicians, T-cell immunologists, and mathematical modelers, who have existing, complementary tools and existing collaborations, to rapidly produce and analyze critical data. We will share our results openly and in real time with the international scientific community to assist in managing this global emergency.


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 = -$932 )
2024	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	6	10/16/2023	SUPPLEMENT FOR EXPANSION	-$932
														Subtotal = -$932

Issue Date FY: 2023 ( Subtotal = -$7,187 )
2023	2020	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	6	10/21/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$2,600
2023	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	5	10/21/2022	NON-COMPETING CONTINUATION	-$2,600
2023	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	003	5	11/9/2022	SUPPLEMENT FOR EXPANSION	-$1
2023	2020	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	002	6	11/1/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$7,187
														Subtotal = -$7,187

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	004	6	6/29/2022	SUPPLEMENT FOR EXPANSION	$31,293
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	5	6/13/2022	NON-COMPETING CONTINUATION	-$146,402
2022	2020	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	002	6	6/13/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$146,402
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	5	10/14/2021	SUPPLEMENT FOR EXPANSION	$0
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	003	5	6/29/2022	SUPPLEMENT FOR EXPANSION	-$31,293
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $1,626,218 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	5	6/24/2020	NON-COMPETING CONTINUATION	$808,980
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	5	7/15/2020	SUPPLEMENT FOR EXPANSION	$817,238
														Subtotal = $1,626,218

Issue Date FY: 2019 ( Subtotal = $819,943 )
2019	2019	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	4	6/18/2019	NON-COMPETING CONTINUATION	$819,943
														Subtotal = $819,943

Issue Date FY: 2018 ( Subtotal = $820,522 )
2018	2018	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	3	6/20/2018	NON-COMPETING CONTINUATION	$820,522
														Subtotal = $820,522

Issue Date FY: 2017 ( Subtotal = $830,347 )
2017	2017	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	2	6/28/2017	NON-COMPETING CONTINUATION	$830,347
														Subtotal = $830,347

Issue Date FY: 2016 ( Subtotal = $856,521 )
2016	2016	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	6/29/2016	NEW	$856,521
2016	2016	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	1	7/7/2016	NEW	$0
														Subtotal = $856,521

Grand Total All Awards = $4,945,431

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Immunoprotective Properties of Tissue-resident Memory T Cells in Mice and Humans within Mucosal Sites

Award Number: R01AI121129

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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