How antibodies drive complement activation

Summary

Infectious diseases are becoming harder to treat, since bacteria become multiresistant against antibiotics. It is therefore important to develop novel therapies against infections. One possibility is antibody therapy in which therapeutic antibodies are administered to activate the human complement system during an infection. The complement system is a group of blood plasma proteins that work together to kill bacteria that have invaded the body. These proteins however first need to get activated on the bacterial cell surface. In this thesis it is shown that therapeutic antibodies can stimulate this event. The antibodies can form a bridge between the bacterial cell surface and complement proteins by specifically binding both. However, not all types of antibodies can do this effectively. Another goal of this PhD research was therefore to determine which antibodies are most potent in activating complement on bacteria. We therefore studied different steps of the activation process on a molecular level and observed interesting differences between different types of antibodies. This novel basic knowledge about the complement-activating potency of antibodies can be very useful for the development of new antibody therapies against infectious disease.