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High Precision System Analysis of Infant Immune Responses

Award Number: U01AI131386
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/18/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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High Precision System Analysis of Infant Immune Responses - PROJECT SUMMARY This project seeks to surmount current limitations in our understanding of early infant immunity through longitudinal genomic and cellular studies of immune development and primary responses to routine two-month vaccines. Infants and young children are more susceptible to invasive infections than adults owing to overall reduced competency of protective immune responses, including to vaccines, which require administration of multiple doses over several months for adequate long-term protection. While immunization programs have dramatically decreased the global morbidity and mortality caused by infections, it remains that infectious diseases are the most frequent cause of death in infants and young children. The cellular, molecular and genomic mechanisms that contribute to this vulnerability are largely unknown. Ever more powerful tools in genomics and systems biology offer exciting opportunities to resolve these knowledge gaps through detailed analysis of the transcriptomic, epigenomic and functional signatures of infant immune cell populations. However, such studies have been limited by the difficulty in accessing clinical samples from infants, the incompatibility of many genomic technologies for use in small-volume samples, and the lack of bioinformatic tools for integrating and interpreting complimentary yet complex datasets. This proposal will capitalize on our experience studying the infant immune response, our access to infant populations, and our expertise in developing immunogenomic assays for use in human blood-derived immune cells (PBMCs). Specifically, we propose a longitudinal analysis of PBMCs from infants i) at 2, 6 and 12 months, to establish the baseline cellular, phenotypic and genomic signatures of immune development (Aim 1), and ii) at key time points over the course of routine two-month vaccinations, to identify the cellular, phenotypic and genomic signatures associated with primary immune responses to vaccines (Aim 2). We will use an innovative immunogenomic Profiling and Analysis Pipeline (iPAP) we developed that allows us to extract maximal transcriptomic (RNA-seq), epigenomic (ATAC-seq), isoformic (SMRT-seq), cytometric (50-parameter flow cytometry) and immunophenotypic (CyTOF) information from a single infant blood sample, and to integrate these distinct datasets for unparalleled depth of insight into the correlated cellular and genomic signatures of immune development and vaccine responsiveness. Our approach is unbiased, multifaceted and highly technology-driven, combining many of the most cutting-edge genomic and quantitative cell-based technologies with our deep experience in applying these technologies for use in human infant immune cells. In line with the goals of this RFA, this project will yield a comprehensive dataset from infants that can be used to identify fundamental mechanisms and pathways associated with immune development and primary responses to vaccines, and will set the stage for future studies aimed at designing new interventions that induce more potent and protective immune responses for young infants.


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: 2025 ( Subtotal = -$68,839 )
2025	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	5	1/22/2025	SUPPLEMENT FOR EXPANSION	-$65,058
2025	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	5	1/8/2025	NON-COMPETING CONTINUATION	-$3,781
														Subtotal = -$68,839

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	5	11/2/2023	NON-COMPETING CONTINUATION	$0
2024	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	5	1/10/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	5	10/14/2022	NON-COMPETING CONTINUATION	$0
2023	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	004	5	12/28/2022	NON-COMPETING CONTINUATION	$0
2023	2020	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	4	10/14/2022	NON-COMPETING CONTINUATION	$0
2023	2019	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	003	3	11/14/2022	NON-COMPETING CONTINUATION	$0
2023	2018	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	002	2	11/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	5	2/28/2022	NON-COMPETING CONTINUATION	$0
2022	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	002	5	5/25/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	5	3/11/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $1,782,037 )
2021	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	002	5	8/26/2021	SUPPLEMENT FOR EXPANSION	$1,258,393
2021	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	5	8/25/2021	NON-COMPETING CONTINUATION	$0
2021	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	5	8/19/2021	NON-COMPETING CONTINUATION	$523,644
														Subtotal = $1,782,037

Issue Date FY: 2020 ( Subtotal = $2,555,875 )
2020	2020	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	002	4	8/11/2020	SUPPLEMENT FOR EXPANSION	$1,668,904
2020	2020	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	3	6/18/2020	SUPPLEMENT FOR EXPANSION	$360,758
2020	2020	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	4	7/27/2020	NON-COMPETING CONTINUATION	$526,213
														Subtotal = $2,555,875

Issue Date FY: 2019 ( Subtotal = $522,868 )
2019	2019	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	3	7/30/2019	NON-COMPETING CONTINUATION	$522,868
2019	2019	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	002	3	8/21/2019	NON-COMPETING CONTINUATION	$0
2019	2018	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	2	5/2/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $522,868

Issue Date FY: 2018 ( Subtotal = $882,108 )
2018	2018	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	2	7/26/2018	NON-COMPETING CONTINUATION	$518,859
2018	2018	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	2	8/9/2018	NON-COMPETING CONTINUATION	$363,249
														Subtotal = $882,108

Issue Date FY: 2017 ( Subtotal = $527,677 )
2017	2017	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	1	8/8/2017	NEW	$527,677
														Subtotal = $527,677

Grand Total All Awards = $6,201,726

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High Precision System Analysis of Infant Immune Responses

Award Number: U01AI131386

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 06/18/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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