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Polyclonal Bi-Specific Vectored ImmunoTherapy to Functionally Cure HIV Infection

Award Number: DP1DA060607
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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Polyclonal Bi-Specific Vectored ImmunoTherapy to Functionally Cure HIV Infection - Project Summary / Abstract This proposal describes the framework of a DP1 grant for Alejandro B. Balazs, PhD. Dr. Balazs is currently an assistant professor at Harvard Medical School and a principal investigator at the Ragon Institute of MGH, MIT & Harvard. Dr. Balazs' research is focused on engineering the immune system via gene transfer as a novel means of creating protection against infectious disease. This proposal represents an entirely new research direction for his laboratory and is focused on the creation of vectors capable of producing multi-specific polyclonal antibodies in vivo which can neutralize both the highly-mutable HIV-1 virus as well as addictive substances. These will test the hypothesis that engineered polyclonal immune responses can permanently suppress HIV-1 infection more effectively than separate antibodies. The proposal aims to test this concept by first comparing multiple designs of vectors engineered to produce multi-specific antibodies that can both neutralize HIV in a series of cell-based assays. Designs with optimal activity will advance to testing in both mouse and non-human primate models to identify those with maximal expression potential in vivo. Optimal designs will be tested in animal models of HIV- infection. These experiments aim to determine whether polyclonal engineered immune responses can more effectively control HIV replication than multiple individual antibodies while resisting the emergence of escape mutants to achieve a functional cure of HIV infection in people with substance use disorders. Such a finding would have profound implications for treatment of HIV in the context of substance use disorder offering an improved therapeutic intervention against HIV, particularly for people who are unable to comply with existing antiretroviral drug regimens. Moreover, this technology will also test the development of a single therapeutic intervention targeting both HIV and addictive substances, to improve health outcomes for people living with HIV with underlying substance use disorders, consistent with the mission of NIDA and the NIH.


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: 2025 ( Subtotal = $1,052,100 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Drug Use and Addiction Research Programs	001	2	4/14/2025	NON-COMPETING CONTINUATION	$105,210
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	2	3/13/2025	NON-COMPETING CONTINUATION	$946,890
														Subtotal = $1,052,100

Issue Date FY: 2024 ( Subtotal = $1,052,100 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	1	5/13/2024	NEW	$1,009,890
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Drug Use and Addiction Research Programs	001	1	5/22/2024	NEW	$0
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Drug Use and Addiction Research Programs	002	1	7/26/2024	NEW	$42,210
														Subtotal = $1,052,100

Grand Total All Awards = $2,104,200

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Polyclonal Bi-Specific Vectored ImmunoTherapy to Functionally Cure HIV Infection

Award Number: DP1DA060607

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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