High throughput multiplexed characterization and modeling of antibody antigen binding with application to HSV

Abstract All therapeutic antibodies and most vaccines critically depend on the ability of antibodies to specifically recognize particular antigens consequently detailed characterization of antibody antigen binding can provide invaluable information to understand and guide development Unfortunately due to the time and expense required atomic resolution structure determination is typically used sparingly late in a development process or for a small number of different antibodies or antigen variants We seek to enable earlier and larger scale but still detailed characterization and modeling of antibody antigen binding applicable to panels of antibodies that could result from screening polyclonal samples or engineered libraries along with panels of antigens that could result from attempts to understand and account for diversity across populations While not at atomic resolution our approach will still allow residue level localization of specific epitopes for specific antibodies as well as group level identification of functionally similar antibodies and their associated binding regions on the antigen The approach will be enabled by a unique integration of a powerful experimental platform the high throughput multiplexed Wasatch Surface Plasmon Resonance SPR with powerful computational methods to design and analyze binding experiments Studies of glycoprotein D gD of herpes simplex virus HSV will provide a solid foundation for developing testing and applying the technology to better understand critical differences across antibodies and antigenic variation Ultimately the approaches developed here will allow researchers to leverage extensive epitope characterization data generated with Wasatchandapos s SPR instrument in order to broadly and deeply characterize the basis for antibody antigen recognition in wide ranging vaccine and therapeutic antibody discovery and development programs Project Narrative Detailed characterization of antibody antigen binding is fundamental to understanding and potentially improving mechanisms of action of biotherapeutics and vaccines Here in order to support such characterization for large panels of related antibodies and antigen variants computational design and analysis methods will be integrated with a high throughput multiplexed experimental platform enabling the overall grouping of antibodies by binding preferences as well as the detailed localization of particular antibody epitopes By enabling a rich analysis at much higher throughput than traditional structural studies this approach promises to better drive discovery and development of vaccines and therapeutic antibodies