Engineering Stable, Soluble, and Trimeric HIV gp140 by Paired Cys Scanning

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$546,301.00
Award Year:
2012
Program:
SBIR
Phase:
Phase I
Contract:
1R43AI102626-01
Award Id:
n/a
Agency Tracking Number:
R43AI102626
Solicitation Year:
2012
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-123
Small Business Information
3711 MARKET ST, Suite 900, PHILADELPHIA, PA, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
34055645
Principal Investigator:
BENJAMIN DORANZ
(215) 966-6018
bdoranz@integralmolecular.com
Business Contact:
BENJAMIN DORANX
(215) 966-6061
bdoranz@integralmolecular.com
Research Institute:
Stub




Abstract
DESCRIPTION (provided by applicant): When presented with a suitable antigenic Envelope (Env) structure, the human immune system can produce protective antibodies that HIV is unable to evade. Many of the most potently neutralizing HIV antibodies identifiedto date preferentially bind the trimeric structure of Env. Thus, recapitulating the native trimeric structure of Env as it exists on the virus and cell surface is a primary objective in developing an immunogen capable of generating broadly protective humoral immunity. The development of a soluble, trimeric Env structure that recapitulates the native, pre-fusion structure of Env has become a major goal for HIV vaccine advancement. However, the inherent instability of the gp120 and gp41subunit complex has posed a major obstacle in designing a soluble Env trimer (gp140) capable of presenting an effective antigenic structure to the immune system. The goal of this project is to engineer a gp140 variant with disulfide bonds that stabilize the trimer to yield conformationally intact, trimeric gp140. To accomplish the Aims of this project, we will engineer and test up to 10,000 gp140 variants that have been systematically mutated to contain paired disulfide bonds designed to covalently stabilize the protein. Each mutant will be individually expressed in human cells to maintain native post-translational processing, and each mutant will be tested for retention of its pre-fusion conformation, antigenic integrity, and trimeric structure. PUBLIC HEALTH RELEVANCE:This project will contribute to human health by identifying improved gp140 immunogens as vaccine candidates. An improved gp140 immunogen that is stable as a pure, covalently associated trimer and that represents the native gp160 structure as it exists onvirions and cells in its pre-receptor binding, pre-fusion conformation is likely to elcit a potent and broadly neutralizing antibody response against HIV.

* 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

Enviromental Protection Agency logo

National Aeronautics and Space Administration logo

National Science Foundation logo
US Flag An Official Website of the United States Government