Synthetic Antibodies for HIV-1 Vaccines and Diagnostics Development
Antibody phage display has emerged as powerful alternative to hydriboma technology for the identification of monoclonal antibodies and analysis of their interactions with antigens. It is now possible to select high-affinity antibodies against virtually any antigen from phage libraries that bear tailored diversity elements encoded by synthetic DNA ('synthetic antibodies'). This approach obviates the requirements for animal immunization, and greatly reduces the labor and cost of antibody production. Our goal is to harness this technology to advance HIV-1 vaccines and diagnostics development. We will analyze biophysical properties of HIV-1 neutralizing antibodies in a high-throughput manner using synthetic antibody libraries. Most successful prophylactic vaccines elicit neutralizing antiboies, but such protective responses have been difficult to induce for HIV-1. Our studies will provide basic insight into molecular determinants responsible for antigen binding and virus neutralization that will guide subsequent immunogen design. In a second objective, we will create a series of naive antibody libraries for rapid assessment of HIV-1 vaccine development process by bypassing bottlenecks for preliminary testing. Finally, we will develop a low-cost toolkit of affinity reagants to facilitate HIV-1 antigen detection. Current diagnostic immunoassays require expensive antibody-enzyme conjugates that limit their practical use in resource-poor settings. Our goal is to develop phage-based reagants that are simple to use, store, and manufacture.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.