CNN reported recently that the two US citizens who were flown back to the states after contracting the Ebola virus were given an extremely experimental treatment, one that's still undergoing animal testing. While the treatment involves antibodies, it's not a vaccine, and it can work effectively even after an infection has started. The process that produced it is a testament to the impressive capabilities developed in the field of biotechnology.
The Ebola virus, known for its horrific symptoms and high fatality rate, currently has no established treatment. The health care workers who are fighting the disease—and are thus at high risk for becoming infected themselves—can do little more than put themselves in isolation and try to compensate for the damage the virus causes. That situation was apparently the case for two Americans who contracted the virus while working in Liberia.
In this case, however, both people were apparently given an experimental treatment developed in part by a company called Mapp Biopharmaceutical. Complicating matters, Mapp licenses its developments to a company called LeafBio for production and distribution. But LeafBio has also licensed an Ebola treatment from a second company, called Defyrus, and it plans on combining the two. It's unclear whether the Americans received the original or combined therapy. In either case, both therapies were based on the same developmental process outlined below.
Fortunately, Mapp has been publishing papers describing its progress on an Ebola treatment as it went along, so it's possible to understand how the therapy was developed and how it operates. Despite its fearsome behavior, Ebola is a fairly simple virus, with only seven genes. The gene that is essential for the virus to attach to human cells, called Ebola glycoprotein, has been identified previously. Antibodies that stick to this protein would be expected to block infection of new cells and target any virus circulating in the blood stream for destruction. The problem appears to be that an effective antibody response comes too late for the patients. The virus also takes steps to tone down the immune response.
Mapp decided to do the immune system's job for it by making antibodies that can then be injected into infected individuals to perform the same function. The challenges are making the right ones and making enough of them. To get the material they needed, the researchers turned to a well established technology called monoclonal antibody production. They injected mice with the Ebola glycoprotein and then fused individual antibody-producing cells with a cancer cell. This process produced a cell that continued to divide in culture, making a single type of antibody. Some of the antibodies probably recognized cold and flu viruses, so the researchers had to screen for cells that made Ebola-specific antibodies. They identified three that stuck to different parts of the Ebola glycoprotein.
The problem at this point was that the antibodies were from mice. If injected into humans, the human immune system would recognize the antibodies as foreign and start an immune response against the treatment. So Mapp cloned the genes for these antibodies and then swapped out parts, replacing parts of the mouse version with the human portion of the same gene and carefully avoiding alterations in the parts that recognize the Ebola protein.
The researchers then needed to produce the antibodies in large quantities. So they managed to insert the genes into cells from a tobacco plant, which can be grown in large numbers with little fuss. The potential therapy was ready for testing.
Mapp has been pursing that testing, starting in mice and working its way up to primates. The company has also been shifting steadily later into the infection process. Its first tests showed that the treatment could be used prophylactically, given to monkeys prior to infection. In the researchers' most recent published work, from about a year ago, they used it on macaques that were already developing fevers as a result of the infection. Nearly half of the animals survived, while the infection was completely fatal in the control group.
Notably, that paper had members of the US Army Medical Research Institute of Infectious Diseases among its authors, suggesting that further development had a party with deep pockets willing to back the research through human trials. But it's not clear whether those trials had even started when, according to CNN, vials of the treatment were rushed to Liberia. And there's no way of telling how much, if at all, the antibodies helped the two people they were given to. We'll have to wait for larger clinical trials.