On a small plot of land incongruously tucked amid a Kentucky industrial park sit five weather-beaten greenhouses. At the site, tobacco plants contain one of the most promising hopes for developing an effective treatment for the deadly Ebola virus.
The plants contain designer antibodies developed by San Diego-based Mapp Biopharmaceutical Inc. and are grown in Kentucky by a unit of Reynolds American Inc. Two stricken U.S. health workers received an experimental treatment containing the antibodies in Liberia last week. Since receiving doses of the drug, both patients’ conditions have improved.
Tobacco plant-derived medicines, which are also being developed by a company whose investors include Philip Morris International Inc., are part of a handful of cutting edge plant-based treatments that are in the works for everything from pandemic flu to rabies using plants such as lettuce, carrots and even duckweed. While the technique has existed for years, the treatments have only recently begun to reach the marketplace.
“Producing antibodies in plants is faster and less expensive than traditional manufacturing,” said Mary Kate Hart, an immunology researcher who did pioneering research on Ebola antibodies for the U.S. Army. She now is chief scientific officer for DynPort Vaccine Co.
The Ebola virus has sickened 1,711 people in West Africa and killed 932 in the latest outbreak, according to the World Health Organization. The virus has historically killed as many as 90 percent of those who contract it. The current outbreak has claimed the lives of about 60 percent of its victims.
As the disease rapidly spreads in West Africa, threatening the populations and economies in Liberia and neighboring Sierra Leone and Guinea, anxiety is rising around the globe as the international health community gauges the effectiveness of Mapp’s antibody cocktail given to the American aid workers, now said to be recovering at Emory University Hospital in Atlanta.
The path to creating antibodies in tobacco plants starts with mice, which are injected with a vaccine carrying Ebola virus proteins, Erica Ollman Saphire, a molecular biologist at the Scripps Research Institute, said in a telephone interview.
“They come up with a hundred antibodies, and the question is, which ones do you use?” she said.
Researchers try to identify the best antibodies in the lab, before testing them on mice, then eventually on monkeys. Mapp’s experimental drug, dubbed ZMapp, has three antibodies, which work together to alert the immune system and neutralize the Ebola virus, she said.
This is where the tobacco comes in: the plants are used as hosts to grow large amounts of the antibodies. Genes for the desired antibodies are fused to genes for a natural tobacco virus, Charles Arntzen, a plant biotechnology expert at Arizona State University, said in an Aug. 4 telephone interview.
The tobacco plants are then infected with this new artificial virus, and antibodies are grown inside the plant. Eventually, the tobacco is ground up and the antibody is extracted, Arntzen said.
The process of growing antibodies in mammals risks transferring viruses that could infect humans, whereas “plants are so far removed, so if they had some sort of plant virus we wouldn’t get sick because viruses are host-specific,” said Qiang Chen, a plant biologist at Arizona State University in Tempe, Arizona, in a telephone interview.
Ramping Up Development
The Biomedical Advanced Research and Development Authority is exploring whether it’s possible to ramp up the development of ZMapp and if so, how it could be done, said Robin Robinson, the federal agency’s director.
Chen has worked on research producing antibodies in lettuce and tobacco-related plants. His current research focuses on antibodies to combat the West Nile virus.
Few modified-plant derived drugs have made it to market. Pfizer Inc. and Protalix Biotherapeutics Inc.’s enzyme Elelyso, produced in modified carrot cells was approved by U.S. regulators in 2012 to treat Gaucher’s disease.
Locteron, an interferon-based hepatitis C drug candidate derived from duckweed, went through Phase 2 trials before its maker, Biolex Therapeutics Inc., declared bankruptcy.
Neither drug is a monoclonal antibody and so far there has not been a vegetable-grown antibody approved by regulators, Chen said.
Kentucky BioProcessing LLC, founded in 2006, is the manufacturer for ZMapp. Its clients are a mix of private sector firms and government groups, according to spokeswoman Maura Payne. Reynolds American acquired the manufacturer in January this year for an undisclosed amount.
“We’re on a mission to transform the tobacco industry, including driving innovation,” Payne said by telephone. “Given the expertise that is at KBP and what it’s capable of doing with the tobacco plant, clearly we felt they could contribute to transforming the tobacco industry.”
Danny Ebelhar, 66, a tobacco farmer from Owensboro, said he and two other farmers grow tobacco on about 14 combined acres for KBP to use for starch and research other than for pharmaceuticals.
Ebelhar said in the past, KBP inoculated segregated plants in his field under the oversight of federal regulators for possible applications such as a drug-clotting agent. That process was moved indoors at KBP’s controlled environment about four years ago and no longer takes place outdoors, he said.
“Tobacco has always had negative press,” said Ebelhar, 66. “But now it may come back to be a benefit to mankind.’
Another tobacco giant-backed company working on biotech drugs grown in tobacco plants is Medicago Inc. in Quebec City, which is owned by Mitsubishi Tanabe Pharma Corp. and Philip Morris.
Medicago is working on testing a vaccine for pandemic influenza and has a production greenhouse facility in North Carolina, said Jean-Luc Martre, senior director for government affairs at Medicago. Medicago is planning a final stage trial of the pandemic flu vaccine for next year, he said in a telephone interview.
The plant method is flexible and capable of making antibodies and vaccines for numerous types of viruses, said Martre. In addition to influenza, the company’s website says it is in early stages of testing products for rabies and rotavirus.
Medicago ‘‘is currently closely working with partners for the production of an Ebola antibody as well as other antibodies that are of interest for bio-defense,” he said in an e-mail. He would not disclose who the partners were.
Meanwhile, in Owensboro, Kentucky, where ZMapp is made, the town is experiencing a proud moment in the media limelight. The town’s major businesses are health care, aluminum production and mortgage processing, Madison Silvert, president and chief executive of the Greater Owensboro Economic Development Corporation.
The region has pushed to develop life sciences businesses to help diversify the economy and for its potential benefits, he said.
Kentucky BioProcessing’s facility sits in a large industrial park, across from facilities including U.S. Bank Home Mortgage, a Metalsa truck frame manufacturer and Owensboro Manufacturing, a metal stamping company.
A group of about a dozen law enforcement officers were on the KBP property yesterday conducting police dog training in a large field, said John Haller, a retired captain with the Evansville Police Department.
Gary Mattingly, an Owensboro police patrolman, said he’s not sure how widely known the facility’s work is in the community.
“I hope this is the place that does find the cure,” he said.
“It’s tremendous,” Debbie Woodard, who lives nearby, said while walking her bulldog-boxer mix. “Who would have thought something like that would come out of Owensboro, Kentucky?”