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A scalable platform for highly-multiplexed analysis of antibody reactivity from <1uL of blood

Award Number: U24AI152172
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 Antibodies are highly-specific, diverse and widely-assayed biomarkers used to determine recent or historical pathogen exposures, measure the protection conferred by a vaccine, understand the basis of autoimmune diseases or evaluate a host's immunological function. Traditional assays for antibodies focus on one or a small number of reactivities at a time, and so are incommensurate with the scale and diversity of an individual's antibody response. A tool to more holistically interrogate this diversity of reactivities using a small sample volume would enable a new generation of studies in systems immunology, disease association, and epidemiological surveillance. Here, we propose to optimize and significantly extend an approach we have developed for highly- multiplexed, reproducible and inexpensive assays that enable sensitive and high-resolution analysis of antibody reactivity across 100,000s of antigens from <1µL of blood. Our approach takes advantage of a rapid, fully-in- vitro method for generating 100,000s of DNA-barcoded peptides (`PepSeq') as probes for the highly-multiplexed interrogation of serum antibodies using DNA sequencing. As a proof-of-concept, we will be focusing here on an assay targeting all viruses known to infect humans (i.e., the human virome). The virome is an ideal use case for this technology, as viruses represent an incredibly diverse and ubiquitous challenge to the immune system, and because of their small genome sizes, the complete virome can be covered within a single library with minimal loss of diversity. Our preliminary data with this virome assay establishes the feasibility of this approach. Here, we will optimize the assay procedures for multiple sample types in order to increase sensitivity and specificity, while decreasing cost. We will also establish standardized protocols for isotype-specific profiling, adapt the technology to enable antigen-specific, single-cell characterization, and build a suite of open access data analysis and visualization tools to facilitate the use of this technology by the broader research community. Throughout this process, we will generate a panel of anti-virome antibody profiles, including a cohort profiled longitudinally – this data will be made available to the community through the ImmPort portal. If successful, this project will deliver: (i) an optimized assay SOP and library for comprehensive evaluation of pan-viral immunity using a small sample volume, (ii) a large set of publicly-available anti-virome immunity datasets, and (iii) a framework for multiplexed serological assay development that can be directly extended to other targets.


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 = $454,859 )
2024	2024	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE	445 N 5TH ST	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	000	5	3/13/2024	NON-COMPETING CONTINUATION	$454,859
														Subtotal = $454,859

Issue Date FY: 2023 ( Subtotal = $505,400 )
2023	2023	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE	445 N 5TH ST	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	003	4	3/30/2023	NON-COMPETING CONTINUATION	$505,400
2023	2022	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	000	3	11/14/2022	NON-COMPETING CONTINUATION	$0
2023	2022	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE	445 N 5TH ST	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	004	3	9/14/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2021	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	001	2	11/15/2022	NON-COMPETING CONTINUATION	$0
2023	2020	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	002	1	11/16/2022	NEW	$0
														Subtotal = $505,400

Issue Date FY: 2022 ( Subtotal = $566,656 )
2022	2022	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	001	3	4/15/2022	SUPPLEMENT FOR EXPANSION	$61,256
2022	2022	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	000	3	4/1/2022	NON-COMPETING CONTINUATION	$505,400
2022	2022	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	002	3	4/21/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $566,656

Issue Date FY: 2021 ( Subtotal = $843,334 )
2021	2021	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	001	2	4/16/2021	SUPPLEMENT FOR EXPANSION	$337,934
2021	2021	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	000	2	4/9/2021	NON-COMPETING CONTINUATION	$505,400
														Subtotal = $843,334

Issue Date FY: 2020 ( Subtotal = $854,188 )
2020	2020	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	000	1	4/9/2020	NEW	$505,400
2020	2020	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE, THE	445 N 5TH ST STE 600	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	001	1	6/29/2020	SUPPLEMENT FOR EXPANSION	$348,788
														Subtotal = $854,188

Grand Total All Awards = $3,224,437

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A scalable platform for highly-multiplexed analysis of antibody reactivity from <1uL of blood

Award Number: U24AI152172

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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