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Development of a synthetic antibody based on the HIV receptor and co-receptor that is optimized for highly efficient killing of HIV-infected cells by ADCC

Award Number: R43AI120809
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: 06/15/2015
PERIOD OF PERFORMANCE END DATE: 05/31/2016

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Development of a synthetic antibody based on the HIV receptor and co-receptor that is optimized for highly efficient killing of HIV-infected cells by ADCC - ¿ DESCRIPTION (provided by applicant): Eliciting antibodies that neutralize human immunodeficiency virus type-1 (HIV-1) by vaccination is a daunting challenge, due to features of the HIV-1 envelope glycoprotein (Env) that render it inherently resistant to antibody responses, and the extraordinary antigenic diversity that has accrued since the beginning of the HIV-1 pandemic. To circumvent these formidable obstacles, we are pursuing durable in vivo expression of a synthetic neutralizing antibody by gene therapy as an alternative to conventional vaccine approaches. This synthetic antibody (eCD4-Ig) is based on the Env-binding determinants of the viral receptor (CD4) and the viral coreceptor (CCR5). Consequently, eCD4-Ig neutralizes 100% of strains of HIV-1 and simian immunodeficiency virus (SIV) tested thus far, protects rhesus macaques from infection with simian-human immunodeficiency virus (SHIV), and is itself a poor target for host immune responses. Antibody functions in addition to virus neutralization, including antibody-dependent cell-mediated cytotoxicity (ADCC), may substantially augment the ability of eCD4-Ig to prevent systemic infection following exposure to HIV-1. The goal of this project is to maximize the capacity of eCD4-Ig to direct the elimination of virus-infected cells by ADCC. The resulting ADCC-optimized version of eCD4-Ig may confer greater protection against HIV-1 infection, reduce the concentration of eCD4-Ig that must be sustained in plasma and the mucosa to reliably prevent HIV-1 infection, and may increase its effectiveness as a therapeutic in people already infected with HIV-1.


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: 2017 ( Subtotal = $0 )
2017	2015	EMMUNE, INC.	130 SCRIPPS WAY BLDG B ROOM 112	JUPITER	FL	33458	PALM BEACH	USA	Allergy and Infectious Diseases Research	001	1	3/3/2017	NEW	$223,934
2017	2015	EMMUNE, INC.	130 SCRIPPS WAY BLDG B ROOM 112	JUPITER	FL	33458	PALM BEACH	USA	Allergy and Infectious Diseases Research	000	1	11/15/2016	NEW	-$223,934
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $223,934 )
2015	2015	IMMUNATHON, INC.	1 LEIGHTON ST UNIT 1815	CAMBRIDGE	MA	02141	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	1	6/14/2015	NEW	$223,934
														Subtotal = $223,934

Grand Total All Awards = $223,934

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Development of a synthetic antibody based on the HIV receptor and co-receptor that is optimized for highly efficient killing of HIV-infected cells by ADCC

Award Number: R43AI120809

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: 06/15/2015

PERIOD OF PERFORMANCE END DATE: 05/31/2016

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