Virologists at a military laboratory on Fort Detrick may have developed a treatment for a viral ‘cousin’ of Ebola.
Andrew Herbert and John Dye, of the U.S. Army Medical Research Institute of Infectious Diseases, are authors on a recently published paper in the official journal of the National Academy of Sciences about a proposed antibody cocktail for Sudan virus, which is one of six species that falls under the ebolavirus aegis. In an email, Herbert and Dye referred to it as a genetically-distinct cousin of Ebola Zaire, a virus responsible for more than 2,200 deaths in the Democratic Republic of Congo. Sudan virus and Ebola Zaire are genetically different.
Sudan virus has the potential to cause an outbreak, Herbert and Dye said. It has already caused eight confirmed outbreaks in African countries, infecting 779 and resulting in 412 deaths, according to the paper.
One of the most recent was in a rural region of Uganda. More than 450 people were infected, with about half dying from Sudan virus, Herbert said. If it was in a more populous area, the outbreak would have likely been worse.
Dye has been working on Sudan virus since the beginning of his career, he said. Antibody-based immunotherapies for the disease did not exist prior to the research detailed in the paper.
Therapies and vaccines used for Ebola Zaire, including the new Food and Drug Administration approved Merck vaccine, do not work for Sudan Virus because the disease species are genetically distinct, Dye and Herbert said in an email.
Those therapies and vaccines got much of the attention among filovirus research, Herbert said, which made sense because it had a large number of human cases. But that led to a void in the research on Sudan virus, which can have a high fatality rate.
“The Sudan virus is very closely related to that Zaire Ebola virus, but it sort of took a backseat to Zaire for a number of years,” Herbert said.
Sudan virus threatens public health as much as Ebola Zaire, Herbert said, “even though it may not get as much publicity or notoriety.”
Part of USAMRIID’s mission is to prepare for the unexpected, Dye said, which could include a potential Sudan Virus outbreak.
“And this allows us to be prepared ahead of time for a potential pandemic type event with a virus that is closely related to Ebola virus Zaire,” Dye said. “And if we have something in the freezer, that can be pulled out in a moment’s notice, and executed into a clinical trial. We are miles ahead of being able to respond both here at USAMRIID but also globally.”
While the antibody cocktail is in early research stages and has only been tested in animal models, it is now available for emergency use, Dye said.
To create the antibody cocktail, Dye and Herbert’s research team focused on antibodies that would both neutralize the virus and prevent it from entering cells, they said in an email. They focused on antibodies that would be able to bind to a part of the virus, called a glycoprotein, which is a protein on the surface of the virus used to help the virus enter and infect cells, Herbert said.
To decide what antibodies to use, the research team first experimented in cells to see what antibodies best blocked the infection. Then they tested the best antibodies, individually, in mice to see which ones protected the mice best, Herbert and Dye said.
Testing in mice gave them two lead antibody candidates, which they combined into a cocktail they called RIID-F6H2. They then tested the cocktail in macaque monkeys.
The cocktail completely protected the monkeys, they said.
“Importantly, RIID-F6H2 was effective when given to the macaques 4 days after they were infected, and virus could be detected in the blood of these animals,” Herbert and Dye said in the email. “This is an important clinical milestone if you consider an outbreak scenario, where people usually don’t show up to the hospital until they are sick and the virus is detectable in their blood.”
Macaques are a good model to compare to humans, Herbert said. But while the animal is a good model, it is not a human, so further testing would need to be done to see how the cocktail works for humans.
The paper is the first proof of concept for an antibody cocktail for Sudan virus, Herbert said. From there, the cocktail has the ability to move to advanced development, as part of the path toward licensure.
The advanced development stage would likely be outsourced, Dye said.
One company interested in the advanced development stage is Frederick-based Biofactura, said CEO and President Darryl Sampey, one of the authors on the paper.
Sampey said he is investigating the possibility of being the company to take the cocktail to advanced development.
Biofactura has done similar work with antibody cocktails with diseases like smallpox and Marburg virus, which is a hemorrhagic fever virus. The company is able to scale up drugs, such as the antibody cocktail for Sudan virus, which is necessary before it could move to a phase 1 clinical trial, Sampey said.
“So it’s a pretty critical product to have if something happens and a product like that is needed whether it’s an outbreak say in Africa or something that gets out of the lab or any other man made intentional release,” Sampey said. “We need to be prepared and ready with these kinds of countermeasures to be able to treat people and a response to something that’s threatening the lives of the warfighter and the civilian population.”