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A novel approach for deep phenotyping the CD4 T cell response to Mycobacterium Tuberculosis

Award Number: R21AI149311
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/18/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2022

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A novel approach for deep phenotyping the CD4 T cell response to Mycobacterium Tuberculosis - PROJECT SUMMARY Mycobacterium tuberculosis (Mtb) caused 1.3 million global deaths in 2017, yet an effective vaccine remains elusive. A major challenge in the field has been selecting which Mtb antigens (from among >4000 proteins) to include in a vaccine, and what T cell functions it should aim to elicit. Previous attempts to define protective immunity against Mtb have shown mixed success and have focused on diversity in one dimension at a time – eg using proteins / lyates to identify diverse CD4 T cell states (eg cytokine polyfunctionality), or defining cytokine production in response to diverse peptides predicted to bind human leukocyte antigens (HLAs). We hypothesize that deep, simultaneous analysis of both T cell specificity and phenotype will: (i) reveal an interdependence between these 2 dimensions of the anti-Mtb response that is not currently well-understood, and (ii) enable, in future studies, improved correlates of protection against disease that can empower vaccine studies and inform treatment strategies. To achieve this new `deep-2D' view of the response, we propose to integrate 2 novel technologies: (i) a platform we recently developed for experimentally screening the Mtb proteome for peptides that bind diverse HLA class II proteins (`PepSeq'), and (ii) single cell sequencing, enabling linked analysis of transcriptome and peptide:HLA binding within thousands of T cells. If successful, this project would establish a rationale and toolkit for `deep-2D' analysis of the T cell response to Mtb that we could subsequently apply to larger cohorts designed to reveal correlates of disease protection in both natural history and vaccine settings. The approach would also be directly applicable to other complex pathogens.


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: 2023 ( Subtotal = $0 )
2023	2021	TRANSLATIONAL GENOMICS RESEARCH INSTITUTE	445 N 5TH ST	PHOENIX	AZ	85004	MARICOPA	USA	Allergy and Infectious Diseases Research	000	2	9/12/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $280,275 )
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	1/13/2021	NON-COMPETING CONTINUATION	$280,275
														Subtotal = $280,275

Issue Date FY: 2020 ( Subtotal = $255,206 )
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	2/18/2020	NEW	$255,206
														Subtotal = $255,206

Grand Total All Awards = $535,481

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A novel approach for deep phenotyping the CD4 T cell response to Mycobacterium Tuberculosis

Award Number: R21AI149311

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/18/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2022

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