Since 2014, the lethal Ebola virus has swept many countries on the planet, particularly Liberia, Sierra Leone, and Guinea in West Africa. Ebola becomes an emerging infectious disease for which there is no known cure. Now, making progress toward a vaccine and therapy against Ebola, researchers reporting in Cell have identified natural human antibodies with the potential to provide broad protection against Ebolaviruses.
Therapies based on monoclonal antibody has shown promise for treatment of Ebola infections. However, one thing that limits their application is that most antibody therapies target just one specific ebolavirus due to their species-specific recognition of the viral glycoprotein (GP). One experimental therapy called ZMappTM, which comprises thress chimeric monclonal antibodies, is specific for Ebola virus, or called Zaire ebolavirus, but is ineffective against two other ebolaviruses known as Sudan virus and Bundibugyo virus.
The genus Ebolavirus is included in the family Filoviridae, order Mononegavirales. In addition to Zaire ebolavirus, Sudan virus and Bundibugyo virus, there are two other virus species that belong to this genus: Ta Forest ebolavirus and Reston ebolavirus. Essentially, it is very difficult to predict which species will cause the next epidemic. So developing a broadly effective therapy that treats all ebolaviruses is a reasonable strategy in the fight against these lethal pathogens.
The new study, led by John Dye at U.S. Army Medical Research Institute of Infectious Diseases, Kartik Chandran at Albert Einstein College of Medicine, and Zachary Bornholdt at Mapp Biopharmaceutical, showed that two potent antibodies from a human survivor might be used as broadly effective immunotherapeutics and vaccines.
The team previously separated 349 different monoclonal antibodies from a survivor of the 2013-16 Ebola epidemic. For this work, by analyzing these antibodies, the team discovered two antibodies, ADI-15878 and ADI-15742, that effectively neutralized all the five ebolavirus species. Treatment with the antibodies protected animals that were exposed to Ebola virus, Bundibugyo virus and Sudan virus.
The researchers then looked at how the antibodies work at a molecular level. These antibodies recognize a critical and conserved element of the viral membrane fusion machinery, and inhibit viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes. Overall, these results could have implications in prevention and treatment of ebolaviruses. (CusAb strives to provide the excellent products such as GFAP Monoclonal Antibody for researchers.)