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Development of multi-modal single-cell technology to dissect epitope specificity to HIV

Award Number: U24AI120134
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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ABSTRACT/SUMMARY: Single-cell genomic technology is transforming modern immunology. Single-cell transcriptomic profiling combined with DNA bar-coding technology is capable of acquiring information on multiple modalities simultaneously; surface receptor quantitation, paired clonotype identity, and genotype can now be measured alongside the transcriptome in relatively routine technology. Extending this rapid technological development in single-cell genomics, it is now possible to probe epitope- specificity of individual antigen-specific cells in a high-throughput fashion. The goal of this proposal is to apply DNA bar-coding technology to build reagents capable of assessing B and T cell specificity to HIV epitopes alongside other single-cell cell readouts, and in a high throughput manner. The development of technology capable of rapid resolution of epitope specific responses would address several needs in HIV research: (i) it would greatly accelerate the discovery of novel broadly neutralizing antibodies against HIV; (ii) it would allow comprehensively profiling of T cell HIV epitopes, allowing more rapid identification of epitopes associated with protective immunity; (iii) it would characterize transcriptional states of HIV-infected cells and accurately assess differences between productively-infected, latently-infected and uninfected bystander cells. In the incumbent grant (i.e. prior funding period), we developed novel methodology to obtain paired clonotype identity and transcriptome data in antigen-specific B cells, including development, validation and benchmarking of a novel bioinformatics algorithm capable of accurately reconstructing paired immunoglobulin gene sequences in vaccine-elicited B cells. Here, we extend our prior work to incorporate additional information: antigen specificity for HIV epitopes. We will use DNA bar-coding technology to develop reagents capable of resolving epitope- specificity of HIV-specific B and T cells in a high throughput fashion. Specifically, we will apply DNA-bar codes to native HIV trimers and gp120 monomers to accelerate identification of B cells producing neutralizing antibodies. We will also develop DNA bar-coded tetramer-based technology to massively profile HIV-specific T cell responses epitope resolution. Lastly, we will build on our ability to simultaneous quantify viral genomes and host cell transcriptome data in single cells and develop methodology to differentiate the transcriptomes from latently-infected, productively-infected, and uninfected bystander cells in HIV infection. These technologies would be broadly applicable to HIV research and would provide high throughput means to identify correlates of protection in several advanced HIV vaccine platforms.


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 = $1,275,335 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	9	7/25/2023	NON-COMPETING CONTINUATION	$615,626
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	9	5/19/2023	NON-COMPETING CONTINUATION	$659,709
														Subtotal = $1,275,335

Issue Date FY: 2022 ( Subtotal = $660,361 )
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	8	6/1/2022	NON-COMPETING CONTINUATION	$660,361
2022	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	7	5/4/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $660,361

Issue Date FY: 2021 ( Subtotal = $660,984 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	002	7	6/1/2021	NON-COMPETING CONTINUATION	$660,984
2021	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	6	4/30/2021	COMPETING CONTINUATION	$87,712
2021	2019	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	4/30/2021	NON-COMPETING CONTINUATION	-$87,712
														Subtotal = $660,984

Issue Date FY: 2020 ( Subtotal = $681,214 )
2020	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	6	4/27/2020	COMPETING CONTINUATION	$681,214
2020	2019	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	1/31/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $681,214

Issue Date FY: 2019 ( Subtotal = $379,584 )
2019	2019	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	4/19/2019	NON-COMPETING CONTINUATION	$379,584
														Subtotal = $379,584

Issue Date FY: 2018 ( Subtotal = $387,616 )
2018	2018	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	4	4/26/2018	NON-COMPETING CONTINUATION	$387,616
														Subtotal = $387,616

Issue Date FY: 2017 ( Subtotal = $395,649 )
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	3	4/12/2017	NON-COMPETING CONTINUATION	$395,649
														Subtotal = $395,649

Issue Date FY: 2016 ( Subtotal = $392,441 )
2016	2016	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	2	7/25/2016	NON-COMPETING CONTINUATION	$392,441
														Subtotal = $392,441

Issue Date FY: 2015 ( Subtotal = $399,581 )
2015	2015	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	6/17/2015	NEW	$399,581
														Subtotal = $399,581

Grand Total All Awards = $5,232,765

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Development of multi-modal single-cell technology to dissect epitope specificity to HIV

Award Number: U24AI120134

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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