Professor / The Scripps Research Institute
The Scripps Research Institute 10550 North Torrey Pines Road, TRY – 21 La Jolla, CA 92037
Professor Ward leads a diverse group of structural, biophysical, and computational biologists that ply their wares in the fields of virology, vaccinology and membrane protein biology.
Andrew Ward’s lab is interested in structure-based vaccine design for pathogens such as HIV, as well as other enveloped viruses. They use structural and biophysical techniques to characterize viral glycoprotein interactions with antibodies that create detailed pictures about productive adaptive immune responses.
From this data, they can design optimized immunogens for improved immune responses, and then structurally characterize the antibodies elicited by these designer immunogens in order to iteratively improve their designs. The lab’s primary tool for structural characterization is electron microscopy – negative stain single particle electron microscopy can rapidly identify antibody epitopes and understand polyclonal antibody responses at low resolution. CryoEM, on the other hand, enables resolution of atomic details – this data is particularly useful for molecular design. The Ward lab has generated a wide variety of structural views of HIV envelope glycoprotein trimers bound to broadly neutralizing antibodies.
These views include soluble SOSIP.664 vaccine candidates from many different subtypes all the way down to SIV, as well as the native, membrane derived Env. The extensive glycans on the surface of the Env are key determinants of neutralizing antibody epitopes, and are therefore of particular interest for molecular characterization.
Members of the Ward lab have begun to structurally characterize the co-evolution of Env and neutralizing antibodies within infected patients in a longitudinal manner, allowing them to identify key junctures in broadly neutralizing antibody evolution. The lab uses this data to continually improve trimer immunogen designs such that they mimic the native Env. Finally, members of the Ward lab have also generated several multivalent nanoparticles that display 4, 8 or 20 copies of the Env trimer to be used as vaccine candidates.