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High Resolution Analysis of Env-directed B Cells to Accelerate Vaccine Design

Award Number: P01AI104722
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: 04/01/2014
PERIOD OF PERFORMANCE END DATE: 03/31/2021

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High Resolution Analysis of Env-directed B Cells to Accelerate Vaccine Design - DESCRIPTION (provided by applicant): The long term goal is to elicit broadly neutralizing antibodies, but to forward this objective by defining the Env-specific, vaccine-elicited B cell responses in primates primarily directed at the CD4 binding site. Using this information, through iterative design, we will improve responses directed at this and other conserved neutralizing determinants. Project 1, entitled Immunogen Design and Selection, will generate the HIV envelope glycoprotein-based candidate vaccine immunogens to be analyzed in the HIVRAD. The immunogens will be derived by structure-based design, as well as by selection, and responses to them will be analyzed in the other program components. Project 2, B cell Analysis and Ig Genetics, will examine the diversity of the memory B cell repertoire against selected regions of Env elicited by soluble trimers at both short and longer intervals, by newly designed trimeric imijnunogens, as well as long-lived plasma cells in the bone marrow to examine the impact of regimen on V gene usage and somatic hypermutation. Project 3, Memory B Cell Isolation and Antibody Characterization, will isolate B cells using Env-specific FACS and will characterize the isolated Env-specific antibodies for their epitope specificity to aid immunogen redesign and will also analyze the Env-specific memory IgM compartment following Env-trimer inoculation to look for defects in transition to the IgG compartment. Project 4, Bioinformatics and Structure, will use bioinformatics analysis of deep sequencing of B cell transcripts, obtained from the NHP immunogenicity experiments and to characterize antigen-specific antibody populations that arise in response to immunization. The second focus will be to use x-ray crystallography to determine atomic-level structures of high-interest antibodies in complex with gp120. These efforts will be supported by the Administrative Core A, which will institute a management plan to ensure clear communications within the HIVRAD and the NHP Core B which will house the animals, perform immunogenicity experiments with immunogens from Project 1 and provide samples for the analysis of B cell responses for Projects 2, 3 and 4. RELEVANCE: The overall goal of this HIVRAD, and this Overview, is to elicit broadly neutralizing antibodies to the human pathogen HIV-1. The successful elicitation of such antibodies would be a large step forward toward the goal of generating a broadly effective HIV-1 vaccine and would have a substantial impact on improving human public health.


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 = -$9,420 )
2023	2018	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	5	12/30/2022	NON-COMPETING CONTINUATION	-$9,420
2023	2018	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	11/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = -$9,420

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	9/9/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	2/6/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $2,676,775 )
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	3/30/2018	NON-COMPETING CONTINUATION	$2,676,775
														Subtotal = $2,676,775

Issue Date FY: 2017 ( Subtotal = $2,659,329 )
2017	2017	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	4	3/15/2017	NON-COMPETING CONTINUATION	$2,659,329
														Subtotal = $2,659,329

Issue Date FY: 2016 ( Subtotal = $3,841,632 )
2016	2016	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	3	7/29/2016	NON-COMPETING CONTINUATION	$1,191,343
2016	2016	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	3	3/2/2016	NON-COMPETING CONTINUATION	$2,650,289
														Subtotal = $3,841,632

Issue Date FY: 2015 ( Subtotal = $2,810,461 )
2015	2015	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	2	7/8/2015	NON-COMPETING CONTINUATION	$205,200
2015	2015	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	3/11/2015	NON-COMPETING CONTINUATION	$2,605,261
														Subtotal = $2,810,461

Issue Date FY: 2014 ( Subtotal = $2,659,788 )
2014	2014	SCRIPPS RESEARCH INSTITUTE	10666 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	3/31/2014	NEW	$2,659,788
														Subtotal = $2,659,788

Grand Total All Awards = $14,638,565

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High Resolution Analysis of Env-directed B Cells to Accelerate Vaccine Design

Award Number: P01AI104722

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: 04/01/2014

PERIOD OF PERFORMANCE END DATE: 03/31/2021

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