- Ebola virus infection causes a
severe and often fatal illness, and currently there are no preventive
vaccines or treatment options.
- Emerging monoclonal antibody
therapies are capable of neutralizing only one of the major
disease-causing Ebola viruses.
- Current study has isolated two
natural human antibodies that are effective and affords protection against
all three major strains of Ebola viruses.
Newly discovered human
antibodies can protect against all strains of pathogenic Ebola viruses,
according to a recent multi-institutional research venture involving teams from
academia, the government and the industry.
The Importance of
Identifying an Antibody Effective
Against All Major Ebola Viruses
‘Discovery of two human antibodies effective against all major disease-causing Ebola viruses could lead to the development of vaccines and treatment in the future.’
causes a severe and frequently fatal illness. Ever since the first outbreak in
1976, there have been two dozen outbreaks so far. The largest outbreak recorded
in history occurred in West Africa between 2013-2016,
nearly 30,000 persons and killing up
monoclonal antibody based treatments appear promising. However, even the most
advanced among them, a mixture of three monoclonal antibodies, referred to as ZMappTM,
is effective only against Ebola Zaire and not against the two related Ebola
viruses, the Sudan virus and Bundibugyo
virus which have also been responsible for major outbreaks.
Currently there are no existing vaccine effective against all the three major Ebola viruses
"Since it's impossible to predict which of these agents will cause the
next epidemic, it would be ideal to develop a single therapy that could treat
or prevent infection caused by any known Ebola virus,"
says study co-leader Zachary A.
Bornholdt, Ph.D., director of antibody discovery at Mapp
"Our discovery and characterization
of broadly neutralizing human antibodies is an important step toward that
goal," adds study co-leader, Kartik Chandran, Ph.D., professor
of microbiology & immunology at Albert Einstein College of Medicine.
The study was also co-led by John M. Dye,
Ph.D., chief of viral immunology at the U.S. Army Medical Research
Institute of Infectious Diseases (USAMRIID).
How The Current Study
Identified The Antibody Effective Against All Major Ebola Viruses
Bornholdt and Laura M. Walker, Ph.D., a senior scientist at Adimab, LLC, during
the course of an earlier study, had isolated 349 distinct monoclonal antibodies
from a survivor of the
2013-16 Ebola epidemic.
the present research, the
multi-institutional research team identified that two of those 349 antibodies,
referred to as ADI-15878 and ADI-15742
, were able to strongly neutralize
infection by all five known Ebola viruses in tissue culture.
antibodies were able to afford
protection to animals
(ferrets and mice) that had been exposed to a lethal dose of the three major viruses
, namely the
Ebola virus, Bundibugyo virus and Sudan virus.
Mechanism of Action of
the Protective Ebola Antibody
current research has also been able to outline how these protective antibodies
work. In order to determine this they followed the path of the virus once it
entered the body and the role of the protective antibodies in quelling the
2 neutralizing antibodies encounter the virus in the bloodstream and bind
to glycoproteins on the surface of the virus.
virus with the bound antibody attaches to the host cell and gains entry
into the lysosome, a cellular organelle that contains enzymes to digest
unwanted cellular components as well as foreign material.
enter the host cytoplasm, where it can multiply, the virus has to fuse
with the lysosomal membrane and complete a series of interactions to come
the protective antibodies prevent
the virus from coming out of its self-imposed lysosomal
"prison," and snuffs out the infection at this point.
precisely where the antibodies attach to the glycoprotein molecules and when
and how they act to neutralize Ebola viruses, we can begin to craft broadly
effective immunotherapies," says Dr. Dye. "That knowledge has already
allowed us to create a cocktail of monoclonal antibodies that we are testing in
larger animal models for possible use in treating infected patients," adds
research team has also zeroed in on the human genes that are the
likely source of the immune cells giving rise to
antibodies. The findings of the current study could show the way for
development of treatment options and vaccines to prevent infection.
like to synthesize vaccine immunogens [proteins that trigger antibody
production] that can elicit the same types of broadly protective antibodies in
people," says Dr. Chandran.
- Ebola virus entry into host cells: identifying therapeutic strategies - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617201/)