/ 4 February 2015

Ebola survivors’ blood could aid new disease treatments

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After successfully treating four Ebola patients last year, Emory University in Atlanta is leading a government-funded project that uses blood from survivors of the deadly virus to test a novel way of treating infectious disease.

Traditional vaccines boost the immune system’s response to infections. The new project will inject people with genetic material, such as DNA or RNA, in the hopes of spurring a person’s own cells to make specific antibodies capable of fighting Ebola or other pathogens.

“The person’s body is the factory,” said Dr James Crowe of Vanderbilt University, one of the collaborators on the project. “It’s a cool idea.”

Experts say the method, if proven to be safe and effective, would be faster and cheaper than conventional drug production and could potentially be used to treat illnesses such as seasonal flu or malaria.

Antibodies are typically grown in large vats of mammal cells or in some cases, tobacco plants, such as Mapp Biopharmaceutical’s experimental Ebola treatment ZMapp.

The Defense Advanced Research Projects Agency (Darpa), the Pentagon’s elite research arm, has awarded Emory up to $10.8-million over three years to direct the project.

It will include research teams at the United States Centers for Disease Control and Prevention, the US Army Medical Research Institute of Infectious Diseases and several academic research labs, including the University of Wisconsin-Madison, Rockefeller University, Vanderbilt and Scripps Research Institute.

Getting access to blood samples from survivors of the Ebola outbreak in West Africa has been challenging, but Emory has a distinct advantage in having treated a small number of patients on US soil.

All four of its former patients agreed to take part in the programme, said Rafi Ahmed, director of the Emory Vaccine Center, who is leading the effort.

Ahmed and his colleagues intend to isolate antibodies made by these patients in response to the Ebola virus and, through a series of experiments on animals, identify the most effective ones for fighting an Ebola infection.

The approach is unrelated to an experimental treatment provided to several Ebola patients in the US that involved transfusions of blood plasma from Ebola survivors.

Two approaches
Researchers will take two approaches. In one, they will produce large quantities of Ebola-fighting antibodies that could be infused into patients’ bloodstreams intravenously, a conventional approach known as passive immunisation.

Protection using this method has a short half-life of two to three weeks and the antibodies require refrigeration, which is not always available in countries fighting an infectious disease outbreak.

That is why the team is testing the new method for making protective drugs based on DNA or RNA, rather than the older vaccine technology using killed or weakened viruses to stimulate an immune response, a process that can take several months to manufacture.

“In this method, we are trying to go in as silently as possible,” bypassing the immune response, which may not always work, and directly providing the recipe for a highly effective antibody, said Colonel Daniel Wattendorf, the programme director at Darpa who came up with the new strategy.

Wattendorf said the effort is based on prior, early-stage research with drug manufacturers Novartis and Sanofi determining if they could make vaccines out of ribonucleic acid, or RNA.

“What was particularly intriguing about RNA was that it has no chance of integrating into the human genome,” he said. The effect was temporary.

Seasonal flu
Initially, the technology was being developed in the hopes of protecting soldiers from seasonal flu or germs that cause diarrhoea on the battlefield, but the Ebola outbreak presented an opportunity to accelerate the research.

To succeed, researchers will need to identify an effective delivery system to carry the genetic instructions into the body and learn how to quickly identify the most protective antibodies. The goal is to get the process down to 90 days for most diseases, Wattendorf said.

The group is characterising several Ebola antibody candidates to determine which are the most potent, Ahmed said. At that point, the researchers and Darpa will seek drug company partners.

Testing on people could begin within two years, with the ultimate goal being to have a better weapon in hand before the next Ebola outbreak. – Reuters