Development of a monoclonal antibody cocktail for Ebola virus

MB-003 is a cocktail of 3 monoclonal antibodies, originally developed for the treatment of Ebola Virus Disease. These mAbs bind to non-overlapping epitopes on Ebola virus glycoprotein, and one of the mAbs is also reactive with Sudan, Reston, and Tai Forest virus. The mAbs have been chimerized with a human constant region and expressed using a Rapid Antibody Manufacturing Platform in Nicotiana benthamiana. Individually the mAbs protect mice from lethal challenge prophylactically and two days post-exposure at doses less than or equal to 5mg/kg. When cocktailed, MB-003 protects Rhesus macaques from lethal IM challenge: 1000 pfu, with 100% protection demonstrated when treatment was initiated 1 hour post exposure, 67%-100% protection when initiated 1 or 2 days post exposure, and 43% protection when administered after detection of virus by both RT-PCR and a sustained fever; triggers met 100-120 hours post exposure. The majority of treated survivors display minimal morbidity and no side effects were observed from the treatment regimen in any animals. To improve on efficacy, various combinations of antibodies developed by Public Health Agency of Canada – ZMAb – were used to optimize protection in rodents and primates. The resulting combination of antibodies ZMappTM demonstrated improved efficacy over Zmab or MB-003. It is the result of an unusual partnership involving Mapp Biopharmaceutical, Inc. and Kentucky BioProcessing working with the U.S. government, and Defyrus, Inc. working with the Canadian government. Data to date indicate ZMappTM can provide therapeutic efficacy in non-human primates at least 5 days after infection