Effective antibody function against bacterial pathogens

Antibodies are a cornerstone of human immunity against pathogens and achieve this through multiple mechanisms.

However, pathogens have evolved efficient countermeasures, and many aspects of the molecular requirements of antibody-dependent protection remain unclear.

What is becoming increasingly apparent is that a strong antibody response does not equate functional effect against the pathogen and that only a subset of antibodies might be protective.In this proposal, we will use our new tools that cover antibody discovery, engineering, and functional profiling and apply these to group A streptococci and pseudomonas.

There are no antibody treatments available for these clinically important pathogens today.

In general, the potential of using multiple monoclonals, other subclasses, or harnessing Fc-mediated functions of antibodies are not well explored.

We have established technology to be able to map out all of these aspects of antibody function and aim to determine the best antibody features for in vivo protection.

Using this approach, we have already identified a novel antibody mechanism that mediates protection against streptococci.

This and other antibody mechanisms uncovered in the project will be delineated in detail with our new data-driven live imaging technology and molecular sensors for receptor activity.

Such knowledge will be necessary to develop effective antibody-based antibacterial therapies and diagnostics and will be helpful also for other antibody applications.