Antibody therapy could fight second-most deadly strain of virus
Researchers from Albert Einstein College of Medicine of Yeshiva University and other institutions have developed a potential antibody therapy for Sudan ebolavirus (SUDV), one of the two most lethal strains of Ebola. A different strain, the Zaire ebolavirus (EBOV), is now devastating West Africa. First identified in 1976, SUDV has caused numerous Ebola outbreaks (most recently in 2012) that have killed more than 400 people in total. The findings were reported in ACS Chemical Biology.
Between 30 and 90 percent of people infected with Ebola die after experiencing symptoms of the disease that include fever, muscle aches, vomiting and bleeding. In the current EBOV outbreak, at least 1,500 people have died as of the end of August.
Two U.S. aid workers infected in that outbreak received an experimental treatment called ZMapp, a combination of three different monoclonal antibodies that bind to the protein of the virus. The newly described SUDV treatment also uses monoclonal antibodies, in this case synthetic antibodies designed to target a key molecule on the surface of SUDV called the envelope glycoprotein. (A glycoprotein molecule consists of carbohydrates plus a protein).
"While our antibodies show promise for treatment of SUDV infection, they wouldn't work against the EBOV outbreak now underway in West Africa," said Jonathan Lai, Ph.D., associate professor of biochemistry at Einstein and co-corresponding author of the ACS Chemical Biology paper. "That's because antibodies that kill off one strain, or species, of Ebola haven't proven effective against other strains."
In developing their SUDV therapy, the researchers started with specific antibodies made by mice. These antibodies protect the animals against SUDV infection by binding to the envelope glycoprotein on the surface of the virus. But if used in humans, mouse antibodies could provoke an immune response that would destroy them. Needing a "humanized" version of their mouse antibody, the researchers realized that its molecular structure closely resembled the structure of a commonly used human antibody.
The researchers used that human antibody as a scaffold onto which they placed the Ebola-specific portion of the mouse antibody. They then made variants of the resulting molecule by subtly changing its structure in different ways using a process called "synthetic antibody engineering". Two of these variants proved able to fend off SUDV in specially bred mice. "These two monoclonal antibodies represent potential candidates for treating SUDV infection," said Dr. Lai. He noted that more research is needed before the antibody therapy can be tested on humans.
The study, titled "Synthetic Antibodies with a Human Framework that Protect Mice from Lethal Sudan Ebolavirus Challenge," was published online in ACS Chemical Biology on August 20, 2014. In addition to Dr. Lai, other co-corresponding authors were John M. Dye, Ph.D., of the United States Army Medical Research Institute of Infectious Diseases, and Sachdev S. Sidhu, Ph.D., of the University of Toronto. Other Einstein authors were Jayne Koellhoffer, B.S., Julia Frei, B.S., Nina Liu, and Kartik Chandran, Ph.D. Additional authors are Gang Chen, Ph.D., Hua Long, Wei Ye, B.Sc., Kaajal Nagar, and Guohua Pan, Ph.D., all of University of Toronto, and Samantha Zak of the U.S. Army.
The study was funded by grants from the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health (AI090249, AI088027 and AI09762), the Canadian Institutes for Health Research (MOP-93725) and the Defense Threat Reduction Agency.
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation’s premier centers for research, medical education and clinical investigation. During the 2013-2014 academic year, Einstein is home to 743 M.D. students, 275 Ph.D. students, 103 students in the combined M.D./Ph.D. program, and 313 postdoctoral research fellows. The College of Medicine has more than 2,000 full-time faculty members located on the main campus and at its clinical affiliates. In 2013, Einstein received more than $150 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center –- Einstein’s founding hospital, and three other hospital systems in the Bronx, Brooklyn and on Long Island, Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States. For more information, please visit www.einstein.yu.edu, read our blog, follow us on Twitter, like us on Facebook, and view us on YouTube.
Kim Newman | Eurek Alert!
Learning from Nature: Genomic database standard alleviates search for novel antibiotics
02.09.2015 | Max-Planck-Institut für marine Mikrobiologie
Orang-utan females prefer cheek-padded males
02.09.2015 | Max Planck Institute for Evolutionary Anthropology, Leipzig
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from University of Arizona geoscientists. The study is the first to explain how the steep-fronted plateau formed.
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from...
The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.
Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...
Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.
"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
02.09.2015 | Physics and Astronomy
02.09.2015 | Life Sciences
02.09.2015 | Awards Funding