A detailed view of an antibody from a human survivor of Ebola virus infection is reported in a paper published online this week in Nature Structural & Molecular Biology. This study reveals a new vulnerability site in the virus that could be used for therapeutic and vaccine development.
Ebolaviruses cause severe hemorrhagic fever with up to 90% fatality. Three different ebolaviruses can cause outbreaks in humans: Ebola virus (EBOV), Bundibugyo virus (BDBV) and Sudan virus (SUDV). Most known antibodies can only protect against one ebolavirus. A handful of broadly neutralizing antibodies, which can block multiple ebolaviruses, have been identified. However, most of these antibodies target a region in the virus outer layer-the viral glycoprotein (GP)- which is not always exposed. Some of these antibodies target an exposed region at the base of the GP.
Erica Saphire, Kartik Chandran and colleagues worked with one such base-targeting antibody, ADI-15946, which was isolated from a human survivor of the 2013-2016 Ebola outbreak in West Africa and was previously shown to neutralize EBOV and BDBV, but not SUDV. The authors then generated the crystal structure of the antibody bound to the EBOV GP, which showed that ADI-15946 targets a pocket at the base region of the virus, which constitutes a new vulnerability site. This information allowed the authors to engineer the antibody and broaden its ability to also neutralize SUDV.
Further research is needed explore this new vulnerability site for vaccine development and to determine whether the engineered antibody could be used as a component of an effective therapy against all ebolaviruses.