Novel Mucosal Adjuvant for an HIV DNA Vaccine

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43AI089290-01
Agency Tracking Number: AI089290
Amount: $212,099.00
Phase: Phase I
Program: SBIR
Awards Year: 2010
Solicitation Year: 2010
Solicitation Topic Code: NIAID
Solicitation Number: PHS2010-2
Small Business Information
DUNS: 185576639
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 () -
Business Contact
Phone: (443) 543-5010
Research Institution
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 appealing 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 instructs 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 that 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 coadministration 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.

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government