Scientists at the National Institute of Allergy and Infectious Diseases
(NIAID), part of the National Institutes of Health, and colleagues have
discovered that a single monoclonal antibody—a protein that attacks
viruses—isolated from a human Ebola virus disease survivor protected
non-human primates when given as late as five days after lethal Ebola
infection.
The antibody can now advance to testing in humans as a potential
treatment for Ebola virus disease. There are currently no licensed
treatments for Ebola infection, which caused more than 11,000 deaths in
the 2014-2015 outbreak in West Africa. The findings are described in two
articles to be published online by Science on February 25.
NIAID researchers obtained and tested blood samples from a survivor of
the 1995 Ebola outbreak in Kikwit, Democratic Republic of the Congo, and
discovered the survivor retained antibodies against Ebola.
Investigators from the Institute for Research in Biomedicine in
Switzerland then isolated specific antibodies for potential use as a
therapeutic for Ebola infection. Investigators from the United States
Army Medical Research Institute of Infectious Diseases administered a
lethal dose of Zaire ebolavirus to four rhesus macaques, waited five
days, and then treated three of the macaques with daily intravenous
injections of the monoclonal antibody, known as mAb114, for three
consecutive days. The untreated control macaque showed indicators of
Ebola virus disease and died on day nine, but the treatment group
survived and remained free of Ebola symptoms.
NIAID and Dartmouth College researchers then studied how mAb114
neutralizes the Ebola virus and determined that it binds to the core of
the Ebola glycoprotein, blocking its interaction with a receptor on
human cells. This area of the Ebola glycoprotein, called the receptor
binding domain, was previously thought to be unreachable by antibodies
because it is well-hidden by other parts of the virus, and only becomes
exposed after the virus enters the inside of cells.
This is the first antibody to demonstrate the ability to neutralize the
virus by this interaction between the virus and its cellular receptor.
Together the evidence identifies a novel site of vulnerability on the
Ebola virus and suggests mAb114 could be an effective therapy and
warrants further exploration, according to the authors.
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