News Article

First human antibodies to fight all Ebola viruses found
Date: May 19, 2017
Source: Financial Express ( click here to go to the source)

Featured firm in this article: Mapp Biopharmaceutical Inc of San Diego, CA



There are no vaccines or treatments approved for treating these viruses.

The first natural human antibodies that can neutralise and protect animals against all three major disease-causing Ebola viruses have been discovered by scientists, including one of Indian origin. The findings, published in the journal Cell, could lead to the first broadly effective Ebola virus therapies and vaccines. Ebola infections are usually severe, and often fatal. There are no vaccines or treatments approved for treating these viruses. Monoclonal antibodies, which bind to and neutralise specific pathogens and toxins, have emerged as one of the most promising treatments for Ebola patients.

A critical problem, however, is that most antibody therapies target just one specific Ebola virus. "It would be ideal to develop a single therapy that could treat or prevent infection caused by any known Ebola virus," said study co-leader Zachary A Bornholdt, director of antibody discovery at Mapp Biopharmaceutical company in the US. "Our discovery and characterisation of broadly neutralising human antibodies is an important step towards that goal," said study co-leader, Kartik Chandran, professor at Albert Einstein College of Medicine. In earlier research, the team isolated 349 distinct monoclonal antibodies from a survivor of the 2013-16 Western African Ebola epidemic.

In the current study, the researchers found that two of those 349 antibodies, known as ADI-15878 and ADI-15742, potently neutralised infection by all five known Ebola viruses in tissue culture. Both antibodies were able to protect animals (mice and ferrets) that had been exposed to a lethal dose of the three major agents: Ebola virus, Bundibugyo virus and Sudan virus. Follow-up studies showed that the two antibodies isolated from the Ebola patient work by interfering with a critical step in the process by which ebolaviruses infect cells and then multiply inside them. The two antibodies encounter the virus while it is still in the bloodstream, and bind to glycoproteins (proteins to which carbohydrate chains are attached) that project from its surface.

The virus, with its hitchhiking antibodies still bound to it, then attaches to a cell and enters the lysosome -- a membrane-bound structure within the cell that is filled with enzymes for digesting foreign and cellular components. The virus must then fuse with the lysosome membrane to escape into the host cell's cytoplasm, where it can multiply. However, the antibodies prevent the virus from breaking out of its lysosomal "prison," thus stopping infection in its tracks.

"Knowing precisely where the antibodies attach to the glycoprotein molecules and when and how they act to neutralise Ebola viruses, we can begin to craft broadly effective immunotherapies," said John M Dye, from the US Army Medical Research Institute of Infectious Diseases. "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," said Bornholdt.

The researchers also pinpointed the human genes that are the likely source of the immune cells that produce the two antibodies. Some two dozen Ebola virus outbreaks have occurred since 1976, when the first outbreak was documented in villages along the Ebola River in the Democratic Republic of Congo. The largest outbreak in history -- the 2013-16 Western African epidemic -- caused more than 11,000 deaths and infected more than 29,000 people.