After analyzing the blood of a survivor of the 2013-2016 Ebola outbreak, a team of scientists from academia, industry and the government has discoveredthe first natural human antibodies that can neutralize and protect animals against all three major disease-causing ebolaviruses. The findings, published online in the journal Cell, could lead to the first broadly effective ebolavirus therapies and vaccines.
The genus ebolavirus consists of five known strains: Ebola Zaire (which is also commonly referred to as Ebola virus), Sudan virus, Bundibugyo virus, Tai Forest virus and Reston virus. The first four are known to cause the Ebola virus disease (EVD, also known simply as Ebola) in humans, while the fifth has been known only to affect other primates so far.
In earlier research, Dr. Bornholdt and Laura M. Walker, Ph.D., a senior scientist at Adimab, LLC, isolated 349 distinct monoclonal antibodies from a survivor of the 2013-16 Ebola epidemic. In the current study, the multi-institutional research team found that two of those 349 antibodies, known as ADI-15878 and ADI-15742, potently neutralized infection by all five known ebolaviruses in tissue culture. Both antibodies were also able to protect animals (mice and ferrets) that had been exposed to a lethal dose of the three major agents: Ebola virus, Bundibugyo virus and Sudan virus.
The two antibodies encounter the virus while it’s still in the bloodstream, and bind to glycoproteins (proteins to which carbohydrate chains are attached) that project from its surface. The two antibodies work by binding to the glycoproteins that protrude from the virus’ surface before it has a chance to enter the lysosome. These proteins are essential for helping it escape from the lysosome and, with the antibodies bound to them, the virus is unable to do so and infiltrate the host cell’s cytoplasm. This essentially stops it from replicating and neutralizes the infection.
The researchers also pinpointed the human genes that are the likely source of the immune cells that produce the two antibodies. These and other findings could help speed the development of vaccines to prevent ebolavirus infection.
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