Conformational Stabilization of the HIV-1 Env Trimer

DESCRIPTION (provided by applicant): The goal of this project is to generate an improved HIV-1 vaccine immunogen geared toward antibody responses by engineering an HIV-1 Envelope glycoprotein (Env) trimeric complex that is stabilized in its functionally relevant conformation by application of Avatar's proprietary dityrosine protein stabilization technology. The project breaks into two Specific Aims: (i) identification of constructs in which dityrosine crosslinks form to stabilize Env complexes, and (ii) antigenic and physiochemical analyses of DT stabilized Env trimers identified in (i) above, specifically by antigenic and Biacore analyses, and amino acid, mass spectrometric, and size exclusion chromatographic analyses, respectively. The project will be executed in collaboration between Avatar Medical, LLC and the International AIDS Vaccine Initiative. IAVI will design the constructs for evaluation, and Avatar will generate the DNA constructs required for protein construct expression and evaluation. Avatar and IAVI will jointly generate and purify the protein. IAVI will conduct the antigenic analyses, and Avatar will conduct biophysical characterization, including conducting amino acid and size exclusion chromatographic analysis, and overseeing the mass spectrometric analysis outsourced to Creative Proteomics, Inc. PUBLIC HEALTH RELEVANCE: The goal of this project is to generate an injectable vaccine product that will trigger immune responses that protect against infection by the Human Immunodeficiency Virus by taking a novel approach to protein engineering. The product will specifically trigger production of antibodies in vaccinated individuals that will bind to, and neutralize the virus when it enters the body. The goal is to develop a product that triggers production of antibodies that will bind to any HIV particle, and therefore protect vaccinated individuals, regardless of the strain of virus they are exposed to.