After analyzing the blood of a
survivor of the 2013-16 Ebola outbreaks, a team of scientists from academia,
industry and the government has discovered the first natural human antibodies
that can neutralize and protect animals against all three major disease-causing
Ebola viruses. The findings could lead to the first broadly effective Ebola virus
therapies and vaccines.
Ebola viruses infections are usually
severe, and often fatal. There are no vaccines or treatments approved by the
Food and Drug Administration for treating these viruses. Some two dozen Ebola virus
outbreaks have occurred since 1976, when the first outbreak was documented in
villages along the Ebola River in the Democratic Republic of Congo (formerly
Zaire). The largest outbreak in history -- the 2013-16 Western African epidemic
-- caused more than 11,000 deaths and infected more than 29,000 people.
Monoclonal antibodies, which bind to
and neutralize specific pathogens and toxins, have emerged as one of the most
promising treatments for Ebola patients. A critical problem, however, is that
most antibody therapies target just one specific Ebola virus. For example, the
most advanced therapy -- ZMappTM, a cocktail of three monoclonal antibodies --
is specific for Ebola virus (formerly known as "Ebola Zaire"), but
doesn't work against two related Ebola viruses (Sudan virus and Bundibugyo virus)
that have also caused major outbreaks.
Studies showed that the two antibodies
isolated from the Ebola patient work by interfering with a critical step in the
process by which ebolaviruses infect cells and then multiply inside them. 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 virus, with its hitchhiking antibodies still
bound to it, then attaches to a cell and enters the lysosome -- a
membrane-bound structure within the cell that is filled with enzymes for
digesting foreign and cellular components. The virus must then fuse with the
lysosome membrane to escape into the host cell's cytoplasm, where it can multiply.
However, the antibodies prevent the virus from breaking out of its lysosomal
"prison," thus stopping infection in its tracks.
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