MONOCLONAL ANTIBODY 13C6: ENZYMATIC MANIPULATIONS AND MECHANISM STUDIES

Abstract

Filoviruses are high consequence pathogens and classified as Category A Bioterrorism Agents by the Centers for Disease Control (CDC). Cocktails of antibodies have shown recent success therapeutically against Ebola virus (EBOV) and have garnered interest given the current outbreak in West Africa. Understanding how antibodies protect against EBOV is essential for treatment as well as product development; evaluating individual monoclonal antibodies potentially allows for the evolution of a superior cocktail. 13C6 is a monoclonal antibody (mAb) found in MB-003 (the pre-cursor to ZMAPP) and in ZMAPP. By utilizing modified mouse models and exploring different functional areas of the mAb, it was determined that non-neutralizing mechanisms are utilized. The data presented here suggest that effector cells are crucial for 13C6 efficacy and direct virolysis is possible in vitro when complement sources are available. In addition, it questions the use of traditional neutralization assays as good screening tools for monoclonal antibodies.