Based on WHO statistics, an ongoing outbreak in the Democratic Republic of the Congo has killed more than 2100 individuals (as of Sept, 2019); however, that number is dwarfed by the 11000 who died in the 2014-2016 outbreak in West Africa.
Since then, over 100,000 individuals in the region have been vaccinated with an experimental vaccine that recognizes only one of six Ebola strains. But even reaching people to administer it, much less following-up to assess its effectiveness, is greatly hampered by regional warfare and citizens’ wariness of health workers. Thus it remains unclear how effective the current vaccine is. Given these roadblocks and the lethality of the infection, it is imperative that we rapidly devise therapeutics to save lives after infection.
To move toward that goal, LJI structural biologist Erica Ollmann Saphire, PhD, uses x-ray crystallography and a newer high-resolution electron microscopy (EM) method called cryo-EM to discern the shape of viral proteins that comprise Ebola and related filoviruses at the atomic level. These approaches guide vaccine development but equally importantly provide a blueprint for how to engineer antibodies in the laboratory to neutralize the virus in infected individuals. Dr. Saphire’s laboratory has brought us one step closer to this possibility by determining the 3-D structure of proteins from at least two Ebola strains, as well as the related filovirus known as Marburg.
For example, recently she reported structural analysis of a “nucleoprotein” from one Ebola strain bound to a second viral cofactor, an interaction required for the virus to replicate. That snapshot revealed precise protein-protein contact points, which, interestingly, were common to other Ebola strains. Knowing this suggests that it is feasible to develop one reagent, most likely a monoclonal antibody, to block this interaction in cells infected by multiple Ebola strains. Comparable analysis could also prove useful in designing a versatile “pan-Ebola” vaccine to recognizes more than one strain.
Since Dr. Saphire has arrived at LJI, the institute has become headquarters for the Viral Hemorrhagic Fever Immunotherapeutic Consortium (VIC), which she directs. VIC unites 45 previously competing labs worldwide to develop antibodies recognizing Ebola and other filoviruses as well as arenaviruses such as Lassa virus. This pooling of resources allows multiple experts worldwide to evaluate candidate antibodies and hasten development of treatments against these deadly diseases.