NIAID is advancing research on several investigational Ebola treatments in different stages of development.
Ebola Treatment Research
Currently, there are no approved treatments for Ebola. NIAID is conducting and funding research on several experimental Ebola treatments, with the goal of alleviating suffering and stopping the spread of this disease during future outbreaks.
ZMapp, an investigational Ebola treatment developed by Mapp Biopharmaceutical Inc., is a "cocktail" of three different proteins, called monoclonal antibodies (mAbs). These antibodies bind to three different regions of the glycoprotein of the Ebola virus, inhibiting viral replication.
During initial experiments, the antibodies are produced in tobacco plants specifically bioengineered to produce large quantities of the proteins. Currently, they are produced in a cell line derived from hamster ovaries. When tested in nonhuman primates, ZMapp demonstrated strong antiviral activity and protected the animals from death as late as five days after infection with Zaire Ebola virus. The NIAID Division of Microbiology and Infectious Diseases supported the earlier development and preclinical testing of ZMapp. BARDA is supporting accelerated development and manufacturing activities.
ZMapp was administered under emergency use authorization to Ebola-infected patients in Africa, the United States, and Western Europe. The NIH-led PREVAIL II clinical trial examining the safety and efficacy of ZMapp launched in February 2015 in the United States, Liberia, Sierra Leone, and Guinea. Investigators originally aimed to enroll 200 participants but closed enrollment at the end of January 2016 with 72 participants total as the West Africa Ebola outbreak ended. Results presented in February 2016 indicate the antibody cocktail was well-tolerated and showed promise, but there was insufficient data to determine definitively whether it is a better treatment for Ebola virus disease than supportive care alone.
Additionally, through the NIAID Centers of Excellence for Translational Research program, Erica Ollmann Saphire, Ph.D., of Scripps Research Institute, leads a consortium to study immunotherapeutics against viral hemorrhagic fevers, which identified ZMapp's structure and how it binds to Ebola virus. Dr. Saphire is using this knowledge to test next-generation antibodies for better binding and efficacy.
BCX4430, developed by BioCryst Pharmaceuticals with support from NIAID, is an investigational small molecule drug with broad spectrum antiviral activity, including against Ebola. BCX4430 has protected animals against infection with Ebola and Marburg viruses. BioCryst and NIAID(link is external) launched a Phase 1 clinical study in healthy volunteers in December 2014 to examine the product's safety and determine a treatment dosage.
MAb114 is an experimental Ebola treatment, containing a monoclonal antibody that was isolated from a survivor of the 1995 Ebola epidemic in the Democratic Republic of the Congo. Researchers at NIAID's Vaccine Research Center (VRC), in collaboration with the National Institute of Biomedical Research (INRB) in the DRC and other partners, discovered that the survivor still produced antibodies against Ebola, even eleven years after being infected. They isolated the antibodies from the survivor, tested the most favorable ones in the laboratory and non-human primate studies, and selected mAb114 as the most promising.
To protect cells against Ebola, mAb114 binds to the core of a surface protein on the Ebola virus, blocking its interactions with a receptor on human cells, and preventing Ebola from entering and infecting them. In laboratory testing, a single dose of the antibody protected nonhuman primates from developing symptoms of Ebola, even up to five days after exposure to the virus.
NIAID, with support from the Defense Advanced Research Projects Agency, is advancing the antibody treatment.
In May 2018, a Phase 1, first-in-human trial of mAb114 began at the NIH Clinical Center in Bethesda, Maryland. This trial, which will be testing the antibody for safety and tolerability, will ultimately enroll between 18 and 30 healthy volunteers.
In addition, in response to Ebola outbreaks reported in the DRC in 2018, the INRB also is administering mAb114 to Ebola patients under an expanded access protocol.