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Novel Mucosal Adjuvant for an HIV DNA Vaccine

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
95788
Program Year/Program:
2010 / SBIR
Agency Tracking Number:
AI089290
Solicitation Year:
N/A
Solicitation Topic Code:
NIAID
Solicitation Number:
N/A
Small Business Information
PROFECTUS BIOSCIENCES, INC.
6411 Beckley St BALTIMORE, MD 21224-
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2010
Title: Novel Mucosal Adjuvant for an HIV DNA Vaccine
Agency: HHS
Contract: 1R43AI089290-01
Award Amount: $212,099.00
 

Abstract:

DESCRIPTION (provided by applicant): This document contains proprietary information that Profectus BioSciences requests not be released to persons outside the Government, except for purposes of review and evaluation. Abstract DNA vaccination is an appealin g approach for developing prophylactic and therapeutic vaccines for mucosa tropic pathogens such as HIV. Unfortunately, DNA immunization in the muscle or skin does not induce mucosal immunity. DNA vaccination does, however, offer a unique opportunity to co -express adjuvants that could induce mucosal immunity. Retinoic acid (RA) instructs naove lymphocytes to home to mucosal tissues and Retinaldehyde dehydrogenases (RALDHs) are the key enzymes that convert retinal to RA. The RA receptor (RAR) binds RA and in structs cells to up-regulate mucosal homing molecules and to become RA producers themselves. We propose to use a dominant-positive mutant of the RAR (DP-RAR) 1 RALDH isoform 2 (RALDH2) as a mucosal homing adjuvant(s) for an HIV DNA vaccine. We postulate th at intramuscular administration of plasmids expressing the antigens and the RA-producing adjuvants will trigger mucosal immune responses. We will demonstrate the potential of the RA adjuvant(s) with the following specific aims: (1) demonstrate that coadmin istration of plasmids expressing HIV antigens and DP-RAR 1 RALDH2 will induce mucosal antigen-specific immune responses in mice; and (2) demonstrate that adjuvanting a HIV pDNA vaccine with a RA inducing construct will improve protection against a mucosal challenge in the Vaccinia-HIV virus mouse model. If the DP-RAR 1 RALDH2 adjuvant significantly enhances mucosal immune responses and/or significantly enhances protection from virus challenge, it will be further evaluated in primate studies as components of an advanced HIV DNA vaccine/adjuvant combination in a Phase II SBIR application. 2 PUBLIC HEALTH RELEVANCE: The objective of this project is to develop novel mucosal adjuvants that will improve the efficacy of HIV DNA vaccines. These adjuvants will be based on a constructs such as a dominant-positive retinoic acid receptor and the enzyme RALDH2 that initiate retinoic acid production.

Principal Investigator:

Kenneth C. Bagley
BAGLEY@PROFECTUSBIOSCIENCES.COM

Business Contact:

Jeffrey N. Meshulam
meshulam@profectusbiosciences.com
Small Business Information at Submission:

PROFECTUS BIOSCIENCES, INC.
TECHCENTER@UMBC 1450 SOUTH ROLLING RD. BALTIMORE, MD 21227

EIN/Tax ID: 102057941
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No