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Preclinical Development of Full Length Single Chain

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
95822
Program Year/Program:
2010 / SBIR
Agency Tracking Number:
AI091567
Solicitation Year:
N/A
Solicitation Topic Code:
NIAID
Solicitation Number:
N/A
Small Business Information
PROFECTUS BIOSCIENCES, INC.
6411 Beckley St BALTIMORE, MD 21224-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2010
Title: Preclinical Development of Full Length Single Chain
Agency: HHS
Contract: 1R44AI091567-01
Award Amount: $299,258.00
 

Abstract:

DESCRIPTION (provided by applicant): The positive outcome of the RV144 Phase III vaccine trial (the Thai trial ) that tested an ALVAC-HIV/AIDSVAX B/E prime/boost protocol has prompted the field to refocus on humoral immunity as a means of achieving steril izing immunity. This has also renewed interest in positioned other envelope-based subunit immunogens that may provide a better booster to achieve protection. One such immunogen is the Full Length Single Chain (FLSC) a gp120 human CD4 fusion that replicates the conserved envelope-CD4 complex, a key transition state that all HIV isolates must realize during infection. In 2 rhesus macaque studies, rhFLSC, a surrogate version of FLSC that contains CD4 derived from rhesus macaques, provided statistically signifi cant protection (rapid clearance of post-acute plasma viremia, as well as potent and sustained suppression of tissue viremia) against rectal challenge with R5 tropic, and heterologus SHIV162P3. This observation indicates that FLSC could provide similar eff ects in humans and may provide the foundation for an effective vaccine against HIV. The goal of this project, therefore, is to initiate the preclinical development of FLSC in preparation for its evaluation in Phase I clinical trial as the next step in disc erning whether FLSC can be an effective HIV vaccine. To reach this goal, this Fast Track Phase 1 and 2 project has the following aims. Phase 1 Segment Aim 1. Develop pedigreed HEK293 cell lines suitable for the production of FLSC. Aim 2. Identify and optim ize release assays. Phase 2 Segment Aim 3. Manufacture lots of material suitable for potency studies (Aim 4) and preclinical toxicology (Aim 5). Aim 4. Confirm that FLSC/adjuvant formulation induces CD4i responses in rabbits. Aim 5. Evaluate FLSC in precli nical safety studies. Overall, the single chain complex has emerged as one of the rare envelope-based subunit immunogen that by itself affords protection against mucosal infection with a completely heterologous SHIV. These findings suggest that single chai n complexes should be considered as viable candidates for a vaccine against HIV-1. PUBLIC HEALTH RELEVANCE: The positive outcome of the RV144 Phase III vaccine trial has prompted the field to refocus on defining immunogens that can generate humoral immunity as a means of achieving sterilizing immunity. One such immunogen is the Full Length Single Chain (FLSC) a gp120 human CD4 fusion that replicates the conserved envelope-CD4 complex, a key transition state that all HIV isolates must realize during i nfection. The goal of this project, therefore, is to initiate the preclinical development of FLSC in preparation for its evaluation in Phase I clinical trial as the next step in discerning whether FLSC can be an effective HIV vaccine.

Principal Investigator:

Timothy R. Fouts
4437431110
FOUTS@PROFECTUSBIOSCIENCES.COM

Business Contact:

Jeffrey 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