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Multi-Omics Analysis of Broadly Neutralizing Antibodies and Therapeutic Vaccination

Award Number: P01AI177687
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: 07/11/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Multi-Omics Analysis of Broadly Neutralizing Antibodies and Therapeutic Vaccination - SUMMARY The goal of this P01 program is to define mechanisms of efficacy of broadly neutralizing antibodies (bNAbs) and therapeutic vaccines for HIV-1 in a highly collaborative and multifaceted research program. Our overall hypothesis is that immunologic strategies for HIV-1 cure delay viral rebound both by targeting the viral reservoir and by increasing host antiviral immunity. We will evaluate mechanisms of therapeutic efficacy in both humans and nonhuman primates (NHPs) using coordinated virologic, immunologic, and multi-omic approaches with the goal of developing improved next generation HIV-1 cure strategies. We will apply cutting- edge, high-throughput, multi-omic profiling platforms and integrate these data sets to generate a comprehensive tissue landscape and regulatory network of the viral reservoir and host immune responses. This program builds on our existing studies over the past several years in both humans and NHPs evaluating the ability of bNAbs and therapeutic vaccines to delay viral rebound following discontinuation of antiretroviral therapy (ART). We will first utilize existing samples from these studies to generate hypotheses regarding correlates of delayed viral rebound. We will then perform new interventional studies in NHPs with spatial multi- omic analyses in lymph nodes and gastrointestinal mucosal tissues to test hypotheses in order to define mechanisms of reservoir targeting by bNAbs and therapeutic vaccines. The significance of this program is the potential to define the biologic pathways that lead to delayed viral rebound following ART discontinuation. An improved understanding of partially effective bNAbs and therapeutic vaccines in humans and NHPs will lead to basic research advances that will allow the development of improved next generation HIV-1 cure approaches. To accomplish the goals of this P01 program, we propose the following Projects and Cores: Project 1. Multi-Omics Correlates of Broadly Neutralizing Antibody Efficacy Project 2. Multi-Omics Correlates of Therapeutic Vaccine Efficacy Core A. Administrative Core Core B. Multi-Omics Core Core C. Computational Analysis Core Core D. NHP Core


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: 2026 ( Subtotal = $1,500,997 )
2026	2026	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	4/27/2026	NON-COMPETING CONTINUATION	$1,500,997
														Subtotal = $1,500,997

Issue Date FY: 2025 ( Subtotal = $1,505,858 )
2025	2025	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	5/6/2025	NON-COMPETING CONTINUATION	$1,505,858
														Subtotal = $1,505,858

Issue Date FY: 2024 ( Subtotal = $1,510,625 )
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	5/6/2024	NON-COMPETING CONTINUATION	$1,510,625
														Subtotal = $1,510,625

Issue Date FY: 2023 ( Subtotal = $1,412,696 )
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	7/11/2023	NEW	$1,412,696
														Subtotal = $1,412,696

Grand Total All Awards = $5,930,176

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Multi-Omics Analysis of Broadly Neutralizing Antibodies and Therapeutic Vaccination

Award Number: P01AI177687

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: 07/11/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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