Project 2: Viral entry, antibodies, and structural biology

PROJECT SUMMARY – PROJECT 2: VIRAL ENTRY, ANTIBODIES, AND STRUCTURAL BIOLOGY Studies of viral glycoproteins and their interactions with receptors and antibodies are paramount to vaccine design. Project 2 aims to unveil the architecture and entry requirements of the surface glycoproteins of henipaviruses, mammarenaviruses, and phenuiviruses and provide a deep understanding of antibody

responses against them. We will decipher the principles of humoral immunity against the target viral genera and obtain monoclonal antibodies isolated from vaccine-elicited memory B cells and computationally designed to inform immunogen design and support the development of inhibitors of viral entry. We will structurally

characterize the glycoproteins mediating entry of target viruses, in isolation and in complex with neutralizing antibodies and identified receptors to delineate antigenic maps of viral glycoprotein targets and guide the design of vaccines eliciting potent and protective immunity in Projects 3, 4 and 5. Finally, we will discover and

functionally validate the entry receptor and protease requirements of divergent pathogens present in each viral genus selected to inform cell and tissue tropism and support the development of entry/neutralization assays along with animal challenge models in collaboration with Core D. This highly integrated project will benefit from

the Veesler lab’s world-leading expertise in structural and functional characterization of viral glycoproteins, immunological and serological evaluation of infection- and vaccine-elicited antibody responses and structure-based vaccine design and will involve close interactions with Core C (Baker), Core D (Geisbert), Core

E (Bloom), and will generate foundational knowledge that informs vaccine design in Projects 3, 4 and 5 (King & Stuart).