Preclinical Development of Full Length Single Chain

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$299,258.00
Award Year:
2010
Program:
SBIR
Phase:
Phase I
Contract:
1R44AI091567-01
Award Id:
95822
Agency Tracking Number:
AI091567
Solicitation Year:
n/a
Solicitation Topic Code:
NIAID
Solicitation Number:
n/a
Small Business Information
TECHCENTER@UMBC, 1450 SOUTH ROLLING RD., BALTIMORE, MD, 21227
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
185576639
Principal Investigator:
TIMOTHY FOUTS
(443) 743-1110
FOUTS@PROFECTUSBIOSCIENCES.COM
Business Contact:
JEFFREY MESHULAM
() -
meshulam@profectusbiosciences.com
Research Institution:
n/a
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.

* information listed above is at the time of submission.

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