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Project Aims to Boost Ebola Drug Production

Karen McDonald

Karen McDonald (University of California, Davis)

31 December 2014. A research team at University of California in Davis aims to find new ways of boosting production capacity of the experimental Ebola drug ZMapp. The 1-year project, led by UC-Davis chemical engineering and materials science professor Karen McDonald, is funded by a $200,000 rapid-response grant from National Science Foundation.

The current Ebola outbreak has taken an enormous toll on West Africa and put public health authorities worldwide on alert. World Heath Organization reports as of 24 December nearly 19,500 cases of Ebola reported in the region with 7,588 deaths since the oubreak began. While the outbreak spurned increased R&D activity by academic and industrial labs, no treatments or vaccines are yet available for Ebola.

One promising therapy is a cocktail of engineered antibodies engineered for use in humans called ZMapp, made by the biotechnology company Mapp Biopharmaceutical in San Diego. Mapp Bio derived ZMapp from Nicotiana, a flowering tobacco plant. A test with monkeys reported in August 2013 showed 43 percent of the animals recovered when treated with the antibodies after showing Ebola symptoms. Earlier studies showed all of the test animals were protected against infection when treated with the antibodies an hour after exposure.

The company identified ZMapp as a therapy candidate in January 2014. Mapp Bio, and its commercialization partner LeafBio, produce the treatments using whole tobacco leaves. The company’s process transfers the antibodies into live tobacco leaf DNA with a bacteria, where the antibodies incubate and grow. The plants are then ground up, from which the cultured antibodies are derived and captured as an Ebola therapy.

That process however, is slow and produces only small amounts of usable treatments. As the West Africa Ebola outbreak spread, Mapp Bio made its small stock of ZMapp available for humanitarian purposes, and in August 2014 reported its supply was exhausted.

McDonald and colleagues expect to apply more industrial-scale techniques to quickly expand production of ZMapp. The UC-Davis team plans to adapt the same transfer of enginereed antibodies with bacteria used by Mapp Bio, but culture the antibodies in plant cells in the lab, rather than whole tobacco leaves. If the researchers can grow small quantities of cultured plant cells in the lab, they then expect to expand quantities eventually to a 100-liter bioreactor. Biotechnology companies use these methods to produce medications from microbes, plant, and animal cells.

“Whereas if we can produce it in a bioreactor” says McDonald in a university statement, “a lot of biotech companies and contract manufacturers can do that, and it would allow for much more rapid production.” Global HealthShare Initiative that develops health and economic solutions for low-resource regions, also at UC-Davis, is collaborating with McDonald’s lab on the project.

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