Beginning July 1, 2018

Structure-based Design of Antibodies and Vaccines

Project Abstract

Filoviruses Marburg (MARV), Ravn (RAVV), Ebola (EBOV), Sudan (SUDV) and Bundibugyo (BDBV) cause periodic outbreaks of a highly lethal disease in humans. There are no licensed vaccines against any of these viruses. Clara’s project “Computational design of vaccine candidates based on marburgvirus and ebolavirus membrane-proximal external region and receptor binding domain” is aimed at development and downselection of two vaccine antigens: one for marburgviruses MARV and RAVV and another for ebolaviruses EBOV, SUDV and BDBV. The project involves modeling the three-dimensional structures of human antibodies (Abs) as they engage viral surface proteins. It leverages innovative computational tools developed in the Meiler laboratory for the structure-based design of improved human Abs and immunogens. We will use the Rosetta software platform techniques to design novel structure-based vaccine candidate antigens, using high-resolution structures of antigen-antibody complexes in the GP receptor-binding domain (RBD) and membrane-proximal external region (MPER). We will collaborate with James Crowe for the structural and functional characterization of novel human Abs and vaccines against marburgviruses and ebolaviruses. Further, we will collaborate with Ivelin Georgiev to generate rationally designed epitope-based vaccines. Their protective efficacy against marburgviruses and ebolaviruses in vivo via an external collaboration.

Mentors

Primary: Jens Meiler

Secondary: James E. Crowe, Jr.

Type of Trainee

Postdoctoral Fellow