Researchers have harvested two antibodies from a survivor of a 1995 Ebola outbreak, one of which was so effective at subduing the virus that nonhuman primates given the treatment five days after infection experienced nearly complete protection. While several different cocktails of antibodies that target the Ebola virus are currently being tested, Davide Corti et al. sought to find a single or dual-combination agent that could result in a simpler, yet effective treatment. Monoclonal antibodies harvested from an Ebola survivor 11 years after the 1995 Kikwit outbreak showed potent neutralizing activity against the virus, indicating that the survivor's immune system had maintained its memory of the virus for more than a decade following infection. Three of these monoclonal antibodies demonstrated 25% higher binding capability to the Ebola virus than a component of the ZMapp cocktails of antibodies, which is currently being tested in humans. Corti and his team focused on the two most potent, mAb100 and mAb114. Upon treating macaques with the dual combination twice every 24 hours, beginning one day after infection with Ebola, the group did not experience any Ebola symptoms. Tests of mAb114 alone administered five days after infection showed similar results, suggesting that this antibody could serve as a potent therapeutic for those who contract Ebola, even in relatively late stages.
A second study by Misasi et al. depicts the structure of these two monoclonal antibodies and how they interact with the virus. The results could help facilitate development of therapies and vaccines. Both antibodies work by targeting the glycoprotein (GP), a protein on the surface of the Ebola virus that helps it bind to the membrane of host cells, but the two antibodies target different regions of this protein. The researchers' analysis of these crystallized structures reveals that mAb100 binds to the base of GP, similar to how a commonly tested baseline antibody, KZ52, binds; however, the component of mAb100 that binds to GP is more rotated, and thus can "latch" on to three different units of the protein, as opposed to the single unit to which KZ52 binds. Previous studies have shown that a certain protein loop on the GP must be cleaved in order for the virus to enter a host cell, and results by Misasi et al. show that mAb100 interferes with this cleaving. Analysis of mAb114 shows that this monoclonal antibody works by blocking a key receptor of the virus after the loop has been cleaved. The data suggest that mAb114 is more effective than an antibody used in the ZMapp cocktail - despite targeting the same region of the GP - because it remains bound to the GP after the loop has been cleaved. These results shed more light on why mAB100 and mAb114 are such potent antibodies against Ebola, and may pave the way to therapies to fight the life-threatening virus.