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Respiratory pathogen-specific T cell signatures following vaccination, natural infection, and treatment

Award Number: U19AI118626
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary – Overall The La Jolla HIPC team will focus on pathogens causing infectious diseases of the upper and lower respiratory tract that lead to substantial mortality and morbidity. Our approach is unique and innovative, as it focuses on defining immune signatures (IMS) of antigen-specific CD4 and CD8 T cells generated in response to natural infection with important respiratory pathogens such as SARS-CoV-2, Common Cold Coronaviruses (CCC), influenza, Respiratory Syncytial Virus (RSV) and Mycobacterium tuberculosis (Mtb). Likewise, our Program will investigate IMS of antigen-specific T cells generated following vaccination against a diverse array of pathogens in different platforms like attenuated pathogens (BCG, yellow fever (YF)), purified proteins (acellular Bordetella pertussis (PT) vaccines), viral vectors (J&J, SARS-CoV-2) and mRNA (Moderna and Pfizer). In Project 1, we will perform longitudinal analysis to determine persistence and plasticity of antigen-specific T cell responses following natural SARS-CoV-2 infection and vaccination. We will study T cell responses specific to SARS-CoV-2 following vaccination with different vaccine platforms in previously-unvaccinated donors, and in a longitudinal cohort of vaccinated individuals previously naturally-infected with SARS-CoV-2. In parallel studies, we will analyze T cell responses to SARS-CoV-2 in naturally-infected unvaccinated donors. We will also analyze T cell responses in two previously-enrolled cohorts who received YF and PT vaccinations; in both cohorts the natural evolution and persistence of T cell responses to CCC viruses will be investigated. In Project 2, we will perform longitudinal analysis of the IMS of Mtb-specific T cells. Here, we will build on our progress made during the previous HIPC funding period to characterize the IMS associated with latent and active TB disease as well as BCG vaccination. Specifically, we will characterize the longitudinal IMS of both active and latent TB during treatment. In parallel, we will characterize the longitudinal IMS of adults (re)vaccinated with BCG, and characterize the IMS of Mtb-specific T cells in the lung. In Project 3, we will determine the molecular properties of pathogen-specific lung tissue-resident memory T cells (TRM). Our goal is to establish a single-cell atlas of the transcriptome, epigenome, and T cell receptor (TCR) of antigen-specific lung TRM targeting common pathogens that infects the lungs such as: viral (influenza, RSV, para influenza, meta pneumovirus, SARS-CoV-2, CCC), bacterial (pneumococcus, PT, Mtb) and fungal pathogens. The longitudinal study design will enable assessment of plasticity and persistence of lung TRM cells following natural infection and vaccination. The synergy between Projects will allow the generation of cross- comparable large-scale single-cell T cell signatures for respiratory pathogens/vaccines.


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 = $0 )
2024	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	9	4/3/2024	NON-COMPETING CONTINUATION	$0
2024	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	8	11/21/2023	COMPETING CONTINUATION	$87,183
2024	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	7	11/21/2023	NON-COMPETING CONTINUATION	-$87,183
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $2,391,540 )
2023	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	9	6/1/2023	NON-COMPETING CONTINUATION	$2,391,540
2023	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	8	10/21/2022	COMPETING CONTINUATION	$0
2023	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	8	5/31/2023	COMPETING CONTINUATION	$0
2023	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	003	7	9/15/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $2,391,540

Issue Date FY: 2022 ( Subtotal = $2,391,540 )
2022	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	8	5/9/2022	COMPETING CONTINUATION	$2,391,540
2022	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	7	3/18/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,391,540

Issue Date FY: 2021 ( Subtotal = $3,014,062 )
2021	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	7	6/3/2021	NON-COMPETING CONTINUATION	$2,721,262
2021	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	7	6/9/2021	SUPPLEMENT FOR EXPANSION	$292,800
2021	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	003	6	6/24/2021	EXTENSION WITH OR WITHOUT FUNDS	$94,184
2021	2019	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	5	6/24/2021	NON-COMPETING CONTINUATION	-$94,184
														Subtotal = $3,014,062

Issue Date FY: 2020 ( Subtotal = $3,014,280 )
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	6	5/19/2020	EXTENSION WITH OR WITHOUT FUNDS	$2,721,480
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	6	9/2/2020	SUPPLEMENT FOR EXPANSION	$292,800
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	6	8/20/2020	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $3,014,280

Issue Date FY: 2019 ( Subtotal = $2,720,994 )
2019	2019	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	5/31/2019	NON-COMPETING CONTINUATION	$2,720,994
														Subtotal = $2,720,994

Issue Date FY: 2018 ( Subtotal = $4,556,424 )
2018	2018	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	4	8/22/2018	NON-COMPETING CONTINUATION	$1,562,730
2018	2018	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	4	5/11/2018	NON-COMPETING CONTINUATION	$2,720,922
2018	2018	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	4	9/1/2018	NON-COMPETING CONTINUATION	$272,772
														Subtotal = $4,556,424

Issue Date FY: 2017 ( Subtotal = $3,238,555 )
2017	2017	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	3	5/19/2017	NON-COMPETING CONTINUATION	$2,646,747
2017	2017	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	3	6/27/2017	NON-COMPETING CONTINUATION	$0
2017	2017	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	3	8/16/2017	NON-COMPETING CONTINUATION	$591,808
														Subtotal = $3,238,555

Issue Date FY: 2016 ( Subtotal = $3,015,851 )
2016	2016	LA JOLLA INSTITUTE FOR ALLERGY & IMMUNOLOGY	10355 SCIENCE CENTER DRIVE	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	2	8/11/2016	NON-COMPETING CONTINUATION	$249,821
2016	2016	LA JOLLA INSTITUTE FOR ALLERGY & IMMUNOLOGY	10355 SCIENCE CENTER DRIVE	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	6/2/2016	NON-COMPETING CONTINUATION	$2,766,030
														Subtotal = $3,015,851

Issue Date FY: 2015 ( Subtotal = $2,878,656 )
2015	2015	LA JOLLA INSTITUTE FOR ALLERGY & IMMUNOLOGY	10355 SCIENCE CENTER DRIVE	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	1	8/19/2015	NEW	$41,210
2015	2015	LA JOLLA INSTITUTE FOR ALLERGY & IMMUNOLOGY	10355 SCIENCE CENTER DRIVE	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	003	1	9/3/2015	NEW	$0
2015	2015	LA JOLLA INSTITUTE FOR ALLERGY & IMMUNOLOGY	10355 SCIENCE CENTER DRIVE	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	6/9/2015	NEW	$2,837,446
2015	2015	LA JOLLA INSTITUTE FOR ALLERGY & IMMUNOLOGY	10355 SCIENCE CENTER DRIVE	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	1	8/27/2015	NEW	$0
														Subtotal = $2,878,656

Grand Total All Awards = $27,221,902

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Respiratory pathogen-specific T cell signatures following vaccination, natural infection, and treatment

Award Number: U19AI118626

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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