Experimental Ebola Serum Grown in Tobacco Leaves
By Brenda Goodman, MA
Reviewed by Michael W. Smith, MD
Aug. 4, 2014 -- ZMapp, the experimental treatment rushed to two Americans infected with Ebola in Africa, is grown in specially modified leaves of tobacco -- a plant better known for harming health than healing.
"We complied with a request from Emory University and Samaritan's Purse to provide a very limited amount of ZMapp last week," says David Howard, a spokesman for Reynolds American Services, the parent company of Kentucky BioProcessing. The small biopharma company in Owensboro, KY, has been contracted to grow the drug.
Making the serum is slow, in part, because the plants must be grown for several weeks before they are "infected" with a type of protein. "Basically the plants act like a photocopier of the proteins," Howard says.
Once they're infected, Howard says it takes a week for the plants to make enough of the protein to harvest and distill into a useable drug.
"Talk about transforming tobacco," Howard says.
Serum Hadn't Been Used in Humans Before
Based on the interest in the serum, Howard says Kentucky BioProcessing is actively working on ways to scale up its production.
But before it can be used on a wider scale, it must first go through the formal drug approval process with the FDA. Howard says the plan was to begin that process later this year.
The compound used to treat Dr. Kent Brantly and Nancy Writebol was only formulated in January, according to Larry Zeitlin, PhD, president of Mapp Biopharmaceuticals, the California company that co-developed the drug.
It has been tested in monkeys, but had never before been given to human patients before it was rushed to Brantly and Writebol.
Zeitlin says he hasn't even had a chance to publish a scientific paper on the compound, which is a combination of three antibodies that are thought to help in two ways.
One of the antibodies alerts the immune system to infected cells so they can be destroyed, says Erica Ollmann Saphire, Ph.D. She's a professor of immunology at the Scripps Research Institute in La Jolla, CA. She's been given a government grant to study the antibody cocktail.
Saphire says the other two antibodies probably prevent the virus from making more copies of itself. "We're still trying to figure out exactly how it works," she says. "But it seems to neutralize the virus."
Other experts who study Ebola urged caution with reports of Dr. Brantly's dramatic recovery on the drug.
Thomas Geisbert, MD, professor of infectious disease at The University of Texas Galveston Medical Branch, has been studying the Ebola virus since 1988.
He says news accounts that Brantley's rash disappeared in just an hour after receiving a dose of the drug don't make sense to him.
"When I look at a monkey that has a rash from hemorrhagic fever, small blood vessels have already ruptured," Geisbert says. "It takes some time for the skin to recover."
He says other news accounts have stated that Brantly also received blood from a patient who recovered from the infection. That blood might have had protective factors in it.
He says that makes it hard to sort out what might have helped.
"If we can prove that whatever the treatment was worked, that's fantastic," he says. "That's exciting. But I'm cautiously optimistic, because with this particular outbreak, almost 40 percent of patients survive without treatment. So we want to make sure that it wasn't somebody that was going to survive anyway."
But Saphire says the accounts of Brantly's speedy turnaround seem plausible to her.
"It hasn't been used in humans before, so we didn't know what would happen," Saphire says. "But antibodies in general can be very effective."
"I was worried, because in the studies in monkeys, you can save all of them if you treat within 24 hours. If you wait several days for disease to develop, you save half," she says. She adds that researchers had their fingers crossed that it wouldn't be too late for Brantly and Writebol, who had been infected for days before they received their doses.
But she says that in the animal experiments, the monkeys were given very high doses of the virus, which may have made it harder to treat.
She says she doesn't know how that would compare to health care workers infected in a clinic setting.
Saphire says she expects the first human trials of ZMapp to begin in 2015.
SOURCES: David Howard, spokesman, Reynolds American Services, North Carolina Larry Zeitlin, Ph.D., president of Mapp Biopharmaceuticals, San Diego, Calif. Erica Ollmann Saphire, Ph.D., a professor of immunology at the Scripps Research Institute in La Jolla, Calif. Thomas Geisbert, MD, professor of infectious disease at The University of Texas Galveston Medical Branch, Galveston, Tex.