The Yeast Display Technologies Unit contributes to the effort of the VRC in repertoire analysis, the discovery and the engineering of antibodies/immunogens. The identification of therapeutic antibodies candidates for infectious diseases involves screening and sequences hundreds to thousands of B-cells and subsequence the expression, purification and testing of hundreds of antibodies using labor intensive methods. The yeast display platform allows high-throughput testing large libraries of antibodies (103-105 mAbs) prior to identify high-affinity antibodies that bind an antibody of interest. These immortalized libraries can then use to identify antibodies targeting different epitopes and thus are designed to allow the program to make the most uses of samples that are often limited. Similarly, repertoire analysis using immune libraries immortalized in yeast allows the rapid identification of antigen specific responses that can be tested (and retested) using multiple antigens. Importantly, the Yeast Display Unit approach allows libraries to be generated from B-cell types that cannot easily be tested using traditional approaches. Immunogens and antibody candidates shown to be promising in animal experiments are often in need of improvements to properties such as binding affinity or to reduce off-target binding. Traditional structure-based design approaches are limited in the number of candidate mutation designs (i.e., hundreds of candidates) that can be tested due to the labor involved in expressing, purifying and testing candidates. The coupling of structure-based design with yeast display technologies, allows millions of designs to be tested simultaneously in a high-throughput manner. The Yeast Display Unit currently has projects ongoing in all of these areas, and has established collaborations across the VRC and with outside collaborators for HIV, SIV, Filoviruses, RSV, yellow fever and Zika.
