Scripps labs studying the structure of antibodies to Ebola virus
13 August 2014
Laboratories at The Scripps Research Institute (TSRI) are
investigating antibodies to fight Ebola virus, including the three
experimental antibodies recently used to treat two American health care workers
infected with the virus.
The two Americans received a highly experimental antibody
cocktail called ZMapp, supplied by San Diego-based Mapp
TSRI laboratories of Professor Erica Ollmann Saphire (Photo on the
right) and Assistant
Professor Andrew Ward are studying the structures of these
antibodies using electron microscopy, which creates high-resolution
images by hitting samples with electrons, and X-ray crystallography,
which determines the atomic structure of crystalline arrays of
proteins. Through these images, the team will discover exactly how
the immune system molecules bind to the Ebola virus and stop it from
functioning, a critical step in drug development.
First identified in the Congo in 1976, the Ebola virus causes an
extremely virulent disease that currently leads to death in 25 to
90% of cases. Fruit bats were identified as a reservoir of the virus
in 2006. The fast-moving virus is spread via the blood or other
bodily fluids of an infected person. Outbreaks of the fast-moving
virus, which spreads via the blood or other bodily fluids of an
infected person, have occurred in Uganda and the Democratic Republic
of Congo in recent years. In 2006 a University of Uppsala study also
found that the Ebola virus had killed 5000 gorillas over 2002-4.
“What we’re showing are sites of vulnerability on the surface of
the virus,” said Daniel Murin, a graduate student in the Saphire and
Ward labs. “These are the chinks in the armour of the virus and the
places were you would want your anti-serum to target.”
The ZMapp treatment is still in experimental stages and has not
yet been approved for use outside the two recent cases. According to
Saphire, ZMapp is one of the best antibody cocktails currently
known, but there may still be ways to improve it.
The structure of Ebola virus (centre, light
blue) with the ZMapp antibodies attached (coloured). This structure
was solved using electron microscopy. Photo credit: Daniel
Murin, The Scripps Research Institute.
Professor Saphire is currently leading a $28 million National
Institutes of Health-funded consortium to test antibody cocktails
from laboratories around the world, with the goal of finding the
best for neutralizing Ebola virus. The program is also developing
antibody cocktails to fight other hemorrhagic fever viruses such as
Marburg, Sudan and Lassa viruses.
For decades, scientists thought no antibodies were effective
against Ebola virus, but in 2012, research from the U.S. Army
Medical Research Institute of Infectious Diseases showed that a mix
of antibodies can stop the virus. Other labs around the world were
simultaneously testing other such antibody cocktails with success.
Today, a whole menu of antibodies have been identified as
potentially therapeutic, and researchers are eager to figure out
which combinations are most effective and why. Antibodies are
currently thought to be the best strategy for treating rare and
deadly viruses such as Ebola because they are effective even a
couple of days after exposure, a time period during which a person
could be airlifted to a hospital for treatment.
An ideal antibody cocktail would ease symptoms and improve the
prognosis of infected individuals—it could even work as a
preventative measure, protecting healthcare workers before they
enter an infected area.
The work on the Ebola virus is part of a larger Vaccine and
Global Health Initiative at TSRI, which includes research on
HIV/AIDS, influenza and tuberculosis.
Scripps Research Institute video of Professor Erica Ollmann Saphire
talking about creating a road map for new treatments