BROADimmune: Structural, genetic and functional analyses of broadly neutralizing antibodies against human pathogens

Objectives

The overall goal of this project is to understand the molecular mechanisms that lead to the generation of potent and broadly neutralizing antibodies against medically relevant pathogens and to identify the factors that limit their production in response to infection or vaccination with current vaccines.

This objective will be achieved through:

• high-throughput cellular screens to isolate from immune donors clonally related antibodies to different sites of influenza hemagglutinin
• crystallography and long time-scale molecular dynamics simulation to understand how mutations can increase affinity and broaden antibody specificity
• broad analysis of the antibody response to erythrocytes infected by P. falciparum to identify conserved epitopes on the parasite and to unravel the role of an enigmatic V gene

Crystallography and long time-scale molecular dynamics simulation will be combined to understand how mutations can increase affinity and broaden antibody specificity.