“Game-theoretic Vaccine Design”
Infectious diseases pose an increasing threat due to a combination of globalization, poor treatment management, and evolutionary treatment escape (that is, mutations that escape drug therapies or antibodies elicited by vaccines). The goal of this proposal is to develop highly scalable methods for sequence-based design of antibodies for HIV that exhibit very broad recognition of diverse isolates, leveraging a combination of game theoretic modeling, computational structure design, scalable sequence search, and scalable bi-level combinatorial optimization. The computational design in the combinatorial antibody and virus sequence space could create a new paradigm for developing new biologics by enabling the design of antibodies with increased breadth, high potency, and high similarity to antibodies in the human repertoire.
Co-crystal structure of the antibody VRC01 complexed with the HIV envelope protein GP120, i.e., the native antibody and virus (Left), and the game theoretically designed antibody with the escaping virus (Right). The designed and the native antibodies have escape cost of 7 and 1 respectively. The designed antibody keeps binding to the virus even after 7 mutations from the native, while there is a single mutation after which the native antibody no longer binds to the virus.
Primary: Yevgeniy Vorobeychik
Secondary: Jens Meiler
Type of Trainee