A Factor H-Fc Fusion Therapy for Methicillin-Resistant Staphylococcus aureus Infection
Abstract
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 a preliminary experiment, we showed that FH(18-20)/Fc binds to S. aureus. In this reporting period we completed our first aim, which was to use our plant expression system to produce FH(18-20)/Fc along with two control FH/Fc fusions: one with a mutation that eliminates Fcs ability to activate complement and one with modified Fcs designed to dramatically enhance complement-activating activity. We made significant progress on our second aim, showing that FH(18-20)/Fc blocks binding of human FH to S. aureus. We also began experiments to measure how FH(18-20)/Fc bound to S. aureus affects complement activation. In the remaining grant period we will measure the efficacy of FH/Fc fusions in boosting killing of MRSA by human polymorphonuclear cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2020
- Accession Number
- AD1109489
Entities
People
- Keith L. Wycoff
Organizations
- Planet Biotechnology (United States)