How antibodies and complement orchestrate protective immune responses against bacteria

Antibiotic resistant bacteria form a significant threat to public health and therefore there is a great importance in developing antibody-based therapies to combat bacterial infections. Antibody-mediated activation of the complement system is an important mechanism that could be exploited for use as an effective antibacterial therapy. However, there is limited knowledge of the processes underlying antibody-dependent complement activation of bacteria. For example, it is still not understood why certain antibodies induce bacterial killing while others do not. Therefore, in the project we aim to identify human antibodies that potently induce complement-mediated killing of bacteria and understand their mechanism of action. More specifically, this project aims to (1) develop novel approaches to identify human antibodies recognising E. coli, (2) identify antibodies that drive potent killing of E. coli via MAC and neutrophils, (3) understand functional antibody responses during infections, and (4) unravel the basic mechanisms of antibody-mediated complement activation and subsequent killing of bacteria.

Kulsum Dawoodbhoy & Marije van 't Wout