A Factor H-Fc Fusion Therapy for Methicillin-Resistant Staphylococcus Aureus Infection

The purpose of this project is to develop a new drug for methicillin-resistant S. aureus (MRSA), engineered from two human proteins, that will undermine the mechanism that S. aureus uses to evade detection and destruction by the human immune system. We have produced FH(18-20)/Fc, an engineered protein that combines the S. aureus-binding CCPs from human Factor H with immunoglobulin Fc, an antibody fragment that activates complement on surfaces to which it is bound.In the first reporting period we completed our first aim, which was to use our plant expression system to produce FH(18-20)/Fcalong with two control FH/Fc fusions: one with a mutation that eliminates Fcs ability to activate complement and one with modified Fcs designed to enhance complement-activating activity.In the second reporting period we completed our second aim, showing that FH(18-20)/Fc blocks binding of human FH to S.aureus. We also measured how FH(18-20)/Fc bound to S. aureus affects complement activation. Finally, we measured the efficacy of FH/Fc fusions in boosting killing of MRSA by human polymorphonuclear cells.