For months, Vanderbilt University researcher Dr. James Crowe has been desperately seeking access to the blood of U.S. Ebola survivors, hoping to extract the proteins that helped them overcome the deadly virus for use in new, potent drugs.
His efforts finally paid off in mid-November with a donation from Dr. Rick Sacra, a University of Massachusetts physician who contracted Ebola while working in Liberia. The donation puts Crowe at the forefront of a new model for fighting the virus, now responsible for the worst known outbreak in West Africa that has killed nearly 7,000 people.
"They can take antibodies they find in my blood and map them out,” Sacra said in an interview. “They are looking for the ones that are most important in neutralizing the virus.”
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Sacra, a medical missionary for Christian group SIM USA, said he made the blood donation with “no strings attached” and does not stand to gain financially if a product based on his antibodies reaches the market.
Crowe is working with privately held drugmaker Mapp Biopharmaceutical Inc, which he said will manufacture the antibodies for further testing under a National Institutes of Health grant. Mapp is currently testing its own drug ZMapp, a cocktail of three antibodies that has shown promise in treating a handful of Ebola patients.
Crowe’s hope is to improve on ZMapp by isolating the human antibodies of actual survivors and create a drug effective against all strains of Ebola.
Several leading scientists have embraced the idea of using survivors’ antibodies as the most promising approach in the fight against Ebola.The push is part of the race to develop drugs to address the ongoing outbreak in Sierra Leone, Liberia and Guinea. Canada’s Tekmira Pharmaceuticals Corp is also testing a treatment, while drugmakers including GlaxoSmithKline Plc and Merck & Co, in partnership with NewLink Genetics Corp, are working on vaccines.
Antibodies are immune-system proteins that seek and destroy foreign invaders, such as viruses or bacteria. Crowe, who directs the Vaccine Center at Vanderbilt, is working with Sacra's B cells – white blood cells that form antibodies. They will synthesize genes from the most potent of these antibodies, which can be made into treatments.
All of the antibodies generated in this work will be tested against live Ebola virus samples in a high-security laboratory run by Dr. Thomas Geisbert at the University of Texas Medical Branch in Galveston. Promising candidates will be tested in mice and guinea pigs before going to primates then humans, a process that could take several months.
"We hope to have antibodies that are like ZMapp or better," said Geisbert, who has a $26 million grant from the National Institutes of Health to study experimental Ebola treatments.
A key production issue for ZMapp has been its slow method of growing antibodies in the cells of tobacco plants. In October, Mapp started working with biotechnology company Amgen to mass produce ZMapp antibodies in mammalian cells, a well established manufacturing process.
Crowe estimates human trials could begin in late spring or early summer of 2015.
Crowe's lab has been working on Ebola for the past two years. In that time, he said he has spent "a tremendous amount of effort" trying to get samples from Ebola survivors out of Africa.
Obtaining the samples during the current outbreak has proved nearly impossible, as governments in West Africa struggle to curb the virus and U.S. authorities tighten restrictions around the transfer of highly infectious materials.
As a result, Crowe and his peers in the field have been seeking out the small number of U.S. survivors who were treated in this country.
Scarcity has made the Sacra donation all the sweeter for Crowe and Geisbert.
Crowe believes his luck turned when he mentioned the problem to Dr. Larry Zeitlin, Mapp's president. Zeitlin used his connections with missionary organizations, some of which have used ZMapp to treat their infected staff, Crowe said. Soon after, Sacra volunteered.
While none of the experimental Ebola treatments have been proven effective in rigorous clinical trials, Sacra believes they played a significant role in his own recovery in September. He received Tekmira’s TKM-Ebola and a plasma infusion from fellow survivor, and medical missionary, Dr. Kent Brantly, and said his condition improved immediately.
With a new lease on life, Sacra announced last week that he would return to Liberia to continue his medical work.