To support the creation of Ebola virus vaccines and treatments, Integral Molecular, a leader in membrane protein antibody discovery, has identified the key molecular interactions that mediate the effectiveness of the anti-Ebola ZMappTM therapeutic cocktail.
The treatment is in clinical trials after being used on an emergency basis with select patients during the 2014 Ebola virus outbreak.
Using its proprietary Shotgun Mutagenesis (.pdf) mapping platform, Integral Molecular identified the exact binding sites, or epitopes, of the therapeutic antibodies in the ZMapp, ZMAb, and MB-003 cocktails. This work helps explain why ZMapp has been more effective than other cocktails in treating disease, and provides a design pathway for improved therapeutic drug cocktails.
This work is published in the November 2015 issue of the Journal of Virology and was presented at the American Society of Tropical Medicine and Hygiene (ASTMH) annual meeting in October.
“To accelerate research during the global health threat of Ebola, we made it a priority to apply our high-throughput mapping technology to identify the epitopes of ZMapp,” said Benjamin Doranz, President and CEO of Integral Molecular. “These antibodies are the most important Ebola therapeutics developed to date, but prior to our work there was not enough information about where and how these antibodies acted on their target to prevent infection.”
In October 2014, Integral Molecular was awarded $3,499,900 by the National Institute of Allergy and Infectious Diseases (NIAID) part of the National Institutes of Health (NIH), to discover and characterize B-Cell epitopes on the surface of the enveloped viral pathogens HCV (E1/E2) and EBOV (GP1/GP2), and to determine their contribution to the humoral protection and viral pathogenesis.
A follow-on $5.5M award in October 2015 expanded efforts to discover antibodies against Ebola virus and identify how they prevent Ebola virus infection, research that will significantly impact the development of Ebola therapeutics and vaccines.
Read the paper: Mechanism of Binding to Ebola Virus Glycoprotein by the ZMapp, ZMAb, and MB-0032 Cocktail Antibodies.