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article imageAntibody strategy shows promise against Ebola

By Tim Sandle     Sep 22, 2016 in Science
A recent study, involving a new therapeutic strategy, points towards a weakness with the Ebola virus. Could this Achilles’ heel point towards an anti-Ebola treatment involving antibodies?
With the research, two antibodies, in tests, blocked the invasion of human cells by all five different Ebola viruses. When the study was run again using mice, one combination protected test mice exposed to lethal doses of Ebola strains Zaire and Sudan.
Ebola virus carries a high degree of fatality. There have been two dozen Ebola outbreaks have been documented since 1976, with the most deadly occurring in West Africa during 2014-2015.
Treatments for Ebola are based around monoclonal antibodies. Antibodies bind to and neutralize specific pathogens and toxins. The concern with this approach is that most antibody therapies target only one specific Ebola virus, whereas five different types have been characterized.
With the new research, broad-spectrum antibodies appear to have been developed. Here, the lead researcher, Dr. Jonathan R. Lai explains to Laboratory Manager magazine, why this is important: “It’s impossible to predict where the next Ebola virus outbreak will occur or which virus will cause it.”
He adds that “the best therapy would be a monoclonal antibody that is active against the glycoproteins of all five Ebola viruses—and until our study, no such antibody had demonstrated the ability to do that.”
The new treatment is based around a newly identified weakness with Ebola. In order to infect and multiply in human cells, the virus needs to bind to a host-cell protein called Niemann-Pick C1 (NPC1). The virus attaches to cells via glycoproteins (these are proteins to which carbohydrate chains are attached). The glycoproteins bristle from the Ebola virus’s surface. Examining this mechanism more fully, the research team found that monoclonal antibodies could potentially thwart Ebola virus infections by neutralizing the viral protein that binds to NPC1.
This was achieved by synthesizing two types of “bispecific” antibodies, each consisting of two monoclonal antibodies combined into one molecule. Of these, one bispecific antibody neutralizes the viral protein that binds to NPC1, the other targets NPC1.
The study was performed at the Albert Einstein College of Medicine, supported by the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and other institutions.
The research has been published in the journal Science, in a paper titled “A “Trojan horse” bispecific antibody strategy for broad protection against ebolaviruses.”
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