The Ward lab is interested in structure-based vaccine design for pathogens such as HIV, as well as other enveloped viruses.We use structural and biophysical techniques to characterize viral glycoprotein interactions with antibodies that create detailed pictures about productive adaptive immune responses. From these data we can design optimized immunogens for improved immune responses. We then structurally characterize the antibodies elicited by these designer immunogens and iteratively improve our designs. Our 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 and these data are 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 Env are key determinants of neutralizing antibody epitopes and are therefore of particular interest for molecular characterization. We have begun to structurally characterize the co-evolution of Env and neutralizing antibodies within infected patients in a longitudinal manner, allowing us to identify key junctures in broadly neutralizing antibody evolution. We use these data to continually improve trimer immunogen designs such that they mimic the native Env. Finally, we have also generated several multivalent nanoparticles that display 4, 8, or 20 copies of the Env trimer to be used as vaccine candidates.