Tobacco Brings Hope to Ebola Treatment

When asked about the current Ebola outbreak in Africa, anyone keeping up with the news would express concern about the spread of the disease. Although Ebola seems dangerous but distant to the average American, perhaps we shouldn't think of it as too distant.

In early August, the first of two American aid workers infected with Ebola arrived in the United States. Dr. Kent Brantly and Nancy Writebol contracted the disease while working in West Africa, and were sent to Emory University Hospital's containment unit for patients with dangerous and infectious diseases. A few days into their stay, both Brantly and Writebol were given an experimental drug for Ebola called ZMapp. The drug was beyond secretive, as it has not yet undergone clinical trials in humans. However, the Food and Drug Administration (FDA) has determined that the drug is safe enough to be used on urgently sick patients, a decision which propelled the developer, Mapp Biopharmaceutical Inc. of San Diego, to national attention. The company described their drug as "a cocktail of three ‘humanized' monoclonal antibodies that are manufactured using tobacco plants."

A monoclonal antibody is a manufactured protein that has versatile therapeutic abilities to treat diseases. Traditionally, monoclonal antibodies were derived from mice. To create these proteins, mice were injected with a foreign substance, such as human cancer cells. The mouse's immune system would create an antibody that targeted the cancer cells and attracted other immune cells to destroy it. The antibody would then be isolated and fused into a line of cancer cells, allowing it to be mass produced by the quickly-proliferating cancer cells. However, when these antibodies were injected into patients, they were easily identified by human immune systems as foreign, and therefore were not useful for treating diseases. With the advent of genetic engineering, it became possible to grow monoclonal antibodies in plants ("plantibodies"). Plant-derived proteins are preferable to animal proteins because they are free of mammalian virus vectors. As a result, plants became the factories for producing protein. To create these "plantibodies", scientists insert a segment of DNA into a specific plant bacterium that evolved to transfer DNA into plants. The introduced DNA is then used by the plant as a blueprint to make new proteins.

So why would plant protein production be of any use in the fight against Ebola?

Every virus contains a unique sugar tag on its surface, which is how the human immune system is able to differentiate between human and foreign cells. The Ebola virus itself has its own sugar tag, and the ZMapp "three-antibody cocktail" is essentially a genetically engineered antibody complex that can recognize this sugar tag. This plant-developed antibody can latch on to the virus and immediately activate an immune response against these tagged viruses. This virus-antibody complex then attracts other immune cells, which attack the virus. By providing an antibody template, ZMapp works much more quickly than a vaccine, which would require weeks for the immune system to create its own antibodies to the virus.

Despite the secrecy surrounding ZMapp, it is known that the antibodies are developed in an Australian strain of tobacco known as Nicotiana benthamiana, and it is grown in Kentucky.This particular strain is a common tool in plant molecular biology. The only clinical trial data available for ZMapp at the moment shows that it is 100% effective on monkeys infected with the Ebola virus, even in the later stages of infection. Fortunately, the drug was also completely effective in its use on Brantly and Writebol.

Although the scientific field has known the use of plant-developed monoclonal antibodies for many years, its effectiveness against Ebola has brought it to international attention. Scientists are now developing "plantibodies" against the influenza virus to take advantage of their immediate response in case of a pandemic.

References:

Goldstein, D. A. & Thomas, J. A. Biopharmaceuticals derive from genetically modified plants. Oxford Journals 97, 705-716 (2004).

Blakeslee, S. "Scientists Grow Antibodies in Plants" The New York Times. November 7, 1989.

Blinder, A. & Grady, D. "American Doctor With Ebola Arrives in U.S. for Treatment" The New York Times. August 2, 2014.

University of Nebraska-Lincoln. The Benefits and Risks of Producing Pharmaceutical Proteins in Plants (2004).

Kroll, D. "Ebola 'Secret Serum': Small Biopharma, The Army, And Big Tobacco" Forbes. August 5, 2014.

CDC. Ebola Hemorrhagic Fever (2014).

Gallagher, J. "Ebola: Experimental drug ZMapp is '100% effective' in animal traits" BBC News. August 29, 2014.

Mapp Biopharmaceutical. Ebola Antibody Treatment (2014).

Images:

1. Agroinfiltration: Courtesy of Forbes.

2. Kentucky Bioprocessing: Courtesy of Mapp Biopharmaceutical.