Tobacco-derived 'plantibodies' enter the fight against Ebola

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Tobacco-derived 'plantibodies' enter the fight against Ebola
A picture taken on July 24, 2014 shows staff of the Christian charity Samaritan's Purse putting on protective gear in the ELWA hospital in the Liberian capital Monrovia. An American doctor battling West Africa's Ebola epidemic has himself fallen sick with the disease in Liberia, Samaritan's Purse said on July 27. AFP PHOTO / ZOOM DOSSO (Photo credit should read ZOOM DOSSO/AFP/Getty Images)
A picture taken on July 24, 2014 shows staff of the Christian charity Samaritan's Purse putting on protective gear in the ELWA hospital in the Liberian capital Monrovia. An American doctor battling West Africa's Ebola epidemic has himself fallen sick with the disease in Liberia, Samaritan's Purse said on July 27. AFP PHOTO / ZOOM DOSSO (Photo credit should read ZOOM DOSSO/AFP/Getty Images)
A picture taken on July 24, 2014 shows protective gear including boots, gloves, masks and suits, drying after being used in a treatment room in the ELWA hospital in the Liberian capital Monrovia. An American doctor battling West Africa's Ebola epidemic has himself fallen sick with the disease in Liberia, Christian charity Samaritan's Purse said on July 27. AFP PHOTO / ZOOM DOSSO (Photo credit should read ZOOM DOSSO/AFP/Getty Images)
A picture taken on June 28, 2014 shows members of Doctors Without Borders (MSF) putting on protective gear at the isolation ward of the Donka Hospital in Conakry, where people infected with the Ebola virus are being treated. The World Health Organization has warned that Ebola could spread beyond hard-hit Guinea, Liberia and Sierra Leone to neighbouring nations, but insisted that travel bans were not the answer. To date, there have been 635 cases of haemorrhagic fever in Guinea, Liberia and Sierra Leone, most confirmed as Ebola. A total of 399 people have died, 280 of them in Guinea. AFP PHOTO / CELLOU BINANI (Photo credit should read CELLOU BINANI/AFP/Getty Images)
Health workers wearing protective suits walk in an isolation center for people infected with Ebola at Donka Hospital in Conakry on April 14, 2014. Guinea's Foreign Minister Francois Fall said on April 14 that the west African country had brought the spread of the deadly Ebola virus under control after more than 100 people have died. The outbreak is one of the most deadly, with 168 cases 'clinically compatible' with Ebola virus disease reported, including 108 deaths, the World Health Organization (WHO) said in its latest update on April 14. CELLOU BINANI/AFP/Getty Images
Members of the Guinean Red Cross speak with a resident during an awareness campaign on the Ebola virus on April 11, 2014 in Conakry. Guinea has been hit by the most severe strain of the virus, known as Zaire Ebola, which has had a fatality rate of up to 90 percent in past outbreaks, and for which there is no vaccine, cure or even specific treatment. The World Health Organization (WHO) has described west Africa's first outbreak among humans as one of the most challenging since the virus emerged in 1976 in what is now the Democratic Republic of Congo. CELLOU BINANI/AFP/Getty Images
A woman prepares food at a 'maquis,' a small African restaurant, in Kobakro, outside Abidjan, which now serves various types of meat instead of bushmeat, on April 8, 2014. The Ministry of Health has asked Ivorians, 'particularly fond of porcupine and agouti,' a small rodent, to avoid consuming or handling bushmeat, as an unprecedented Ebola epidemic hit West Africa, claiming more than 90 lives. The virus can spread to animal primates and humans who handle infected meat -- a risk given the informal trade in 'bushmeat' in forested central and west Africa. Photo credit should read ISSOUF SANOGO/AFP/Getty Images
People walk past the sign of a 'maquis,' a small African restaurant which serves bushmeat, in Kobakro, outside Abidjan, on April 8, 2014. The Ministry of Health has asked Ivorians, 'particularly fond of porupine and agouti,' a small rodent, to avoid consuming or handling the meat, as an unprecedented Ebola epidemic hit West Africa, claiming more than 90 lives. The virus can spread to animal primates and humans who handle infected meat -- a risk given the informal trade in 'bushmeat' in forested central and west Africa. ISSOUF SANOGO/AFP/Getty Images
Staff of the 'Doctors without Borders' ('Medecin sans frontieres') medical aid organisation bury the body of a person killed by viral haemorrhagic fever, at a center for victims of the Ebola virus in Guekedou, on April 1, 2014. The viral haemorrhagic fever epidemic raging in Guinea is caused by several viruses which have similar symptoms -- the deadliest and most feared of which is Ebola. SEYLLOU/AFP/Getty Images
A nurse of the 'Doctors without Borders' ('Medecin sans frontieres') medical aid organisation examines a patient in the in-take area at a center for victims of the Ebola virus in Guekedou, on April 1, 2014. The viral haemorrhagic fever epidemic raging in Guinea is caused by several viruses which have similar symptoms -- the deadliest and most feared of which is Ebola. SEYLLOU/AFP/Getty Images
Members and supporters of the Parti Democratique Senegalais (PDS, Senegal's Democratic Party) hold poster showing their leader, former Senegalese president Abdoulaye Wade and his son Karim, and a placard reading 'Macky Ebola Sall' (referring to the current president and the deadly virus) as they rally in front of the party's headquarters in Dakar on April 23, 2014. Senegal's former president Abdoulaye Wade was due to return home on Wednesday after two years abroad following his election defeat, with his son facing jail for corruption. Wade, who held power from 2000 to 2012, moved to France after suffering a bitter defeat to current President Macky Sall, his former prime minister turned arch-rival, in March 2012. SEYLLOU/AFP/Getty Images
Health workers speak to relatives of peolpe infected with Ebola at an isolation center at Donka Hospital in Conakry on April 14, 2014. Guinea's Foreign Minister Francois Fall said on April 14 that the west African country had brought the spread of the deadly Ebola virus under control after more than 100 people have died. The outbreak is one of the most deadly, with 168 cases 'clinically compatible' with Ebola virus disease reported, including 108 deaths, the World Health Organization (WHO) said in its latest update on April 14. CELLOU BINANI/AFP/Getty Images
Health workers walk in an isolation center for people infected with Ebola at Donka Hospital in Conakry on April 14, 2014. Guinea's Foreign Minister Francois Fall said on April 14 that the west African country had brought the spread of the deadly Ebola virus under control after more than 100 people have died. The outbreak is one of the most deadly, with 168 cases 'clinically compatible' with Ebola virus disease reported, including 108 deaths, the World Health Organization (WHO) said in its latest update on April 14. CELLOU BINANI/AFP/Getty Images
Staff of the 'Doctors without Borders' ('Medecin sans frontieres') medical aid organisation carry the body of a person killed by viral haemorrhagic fever, at a center for victims of the Ebola virus in Guekedou, on April 1, 2014. The viral haemorrhagic fever epidemic raging in Guinea is caused by several viruses which have similar symptoms -- the deadliest and most feared of which is Ebola. SEYLLOU/AFP/Getty Images
A worker transports dirt in a wheelbarrow at a center for victims of the Ebola virus in Guekedou, on April 1, 2014. The viral hemmorrhagic fever epidemic raging in Guinea is caused by several viruses which have similar symptoms -- the deadliest and most feared of which is Ebola. SEYLLOU/AFP/Getty Images
Guinean hospital staff and staff of the 'Doctors without Borders' ('Medecin sans frontieres') medical aid organisation listen to a nurse from the aid organisation speak on April 1, 2014, in Guekedou, during a talk about viral hemorrhagic fever. The viral hemorrhagic fever epidemic raging in Guinea is caused by several viruses which have similar symptoms -- the deadliest and most feared of which is Ebola. SEYLLOU/AFP/Getty Images
A Senegalese hygienist demonstrates how to protect oneself against the Ebola virus on April 8, 2014 at Dakar airport, during a visit of the Senegalese health minister to check the safety measures put in place to fight against the virus' spread in western Africa. West Africa's Ebola outbreak is among the 'most challenging' ever to strike since the disease emerged four decades ago, the World Health Organisation (WHO) said on April 8, as the suspected death toll from the virus hit 111. SEYLLOU/AFP/Getty Images
Senegal's health minister Awa Marie Coll Seck (2nd L) listens to Alioune Fall (R), chief doctor of Dakar airport, as she visits Dakar airport on April 8, 2014 to check the safety measures put in place to fight against the spread of the Ebola virus in western Africa. West Africa's Ebola outbreak is among the 'most challenging' ever to strike since the disease emerged four decades ago, the World Health Organisation (WHO) said on April 8, as the suspected death toll from the virus hit 111. SEYLLOU/AFP/Getty Images
A view of gloves and boots used by medical staff, drying in the sun, at a center for victims of the Ebola virus in Guekedou, on April 1, 2014. The viral haemorrhagic fever epidemic raging in Guinea is caused by several viruses which have similar symptoms -- the deadliest and most feared of which is Ebola. SEYLLOU/AFP/Getty Images
A health specialist prepares filtered water at an isolation ward for patients at the Doctors Without Borders facility in Guékedou, southern Guinea. Guinea's President Alpha Conde warned of a 'health emergency' as authorities raced to contain a spiraling Ebola epidemic which has killed 78 people and prompted neighboring Senegal to close its border. SEYLLOU/AFP/Getty Images
Employees of the sanitary control of Conakry airport check passengers before they leave the country on April 10, 2014. International aid organisations launched a series of emergency measures across west Africa on Thursday in a bid to contain one of the worst ever outbreaks of the deadly Ebola virus, which is threatening every country in the region. The tropical bug is thought to have killed more than 110 people in Guinea and Liberia since January, with suspected cases reported in Mali and Sierra Leone and aid workers warning that vital hygiene products could run out. AFP PHOTO / CELLOU BINANI (Photo credit should read CELLOU BINANI/AFP/Getty Images)
Employees of the sanitary control of Conakry airport check passengers before they leave the country on April 10, 2014. International aid organisations launched a series of emergency measures across west Africa on Thursday in a bid to contain one of the worst ever outbreaks of the deadly Ebola virus, which is threatening every country in the region. The tropical bug is thought to have killed more than 110 people in Guinea and Liberia since January, with suspected cases reported in Mali and Sierra Leone and aid workers warning that vital hygiene products could run out. AFP PHOTO / CELLOU BINANI (Photo credit should read CELLOU BINANI/AFP/Getty Images)
Employees of the sanitary control of Conakry airport check passengers before they leave the country on April 10, 2014. International aid organisations launched a series of emergency measures across west Africa on Thursday in a bid to contain one of the worst ever outbreaks of the deadly Ebola virus, which is threatening every country in the region. The tropical bug is thought to have killed more than 110 people in Guinea and Liberia since January, with suspected cases reported in Mali and Sierra Leone and aid workers warning that vital hygiene products could run out. AFP PHOTO / CELLOU BINANI (Photo credit should read CELLOU BINANI/AFP/Getty Images)
Employees of the sanitary control of Conakry airport check passengers before they leave the country on April 10, 2014. International aid organisations launched a series of emergency measures across west Africa on Thursday in a bid to contain one of the worst ever outbreaks of the deadly Ebola virus, which is threatening every country in the region. The tropical bug is thought to have killed more than 110 people in Guinea and Liberia since January, with suspected cases reported in Mali and Sierra Leone and aid workers warning that vital hygiene products could run out. AFP PHOTO / CELLOU BINANI (Photo credit should read CELLOU BINANI/AFP/Getty Images)
A member of the Guinean Red Cross uses a megaphone to give information concerning the Ebola virus during an awareness campaign on April 11, 2014 in Conakry. Guinea has been hit by the most severe strain of the virus, known as Zaire Ebola, which has had a fatality rate of up to 90 percent in past outbreaks, and for which there is no vaccine, cure or even specific treatment. The World Health Organization (WHO) has described west Africa's first outbreak among humans as one of the most challenging since the virus emerged in 1976 in what is now the Democratic Republic of Congo. AFP PHOTO / CELLOU BINANI (Photo credit should read CELLOU BINANI/AFP/Getty Images)
A man reads a newspaper featuring a front page story on the death of Liberian diplomat Patrick Sawyer (pictured with his wife Decontee) who died of the Ebloa virus in Lagos on July 30, 2014. Nigeria is on alert against the possible spread of Ebola after the first confirmed death from the virus in Lagos, Africa's biggest city and the country's financial capital. The victim, who worked for the Liberian government, collapsed at Lagos international airport after arriving on a flight from Monrovia via the Togolese capital Lome, according to the Nigerian government. Doctors Without Borders (MSF) warned that the crisis gripping Guinea, Liberia and Sierra Leone would only get worse and could not rule out it spreading to other countries. AFP PHOTO/PIUS UTOMI EKPEI (Photo credit should read PIUS UTOMI EKPEI/AFP/Getty Images)
A pharmacist searches for drugs in a pharmacy in Lagos on July 26, 2014. Nigeria was on alert against the possible spread of Ebola on July 26, a day after the first confirmed death from the virus in Lagos, Africa's biggest city and the country's financial capital. The health ministry said Friday that a 40-year-old Liberian man died at a private hospital in Lagos from the disease, which has now killed more than 650 people in four west African countries since January. AFP PHOTO / PIUS UTOMI EKPEI (Photo credit should read PIUS UTOMI EKPEI/AFP/Getty Images)
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By Sharon Begley

(Reuters) - Drugmakers' use of the tobacco plant as a fast and cheap way to produce novel biotechnology treatments is gaining global attention because of its role in an experimental Ebola therapy.

The treatment, which had been tested only in lab animals before being given to two American medical workers in Liberia, consists of proteins called monoclonal antibodies that bind to and inactivate the Ebola virus.

For decades biotech companies have produced such antibodies by growing genetically engineered mouse cells in enormous metal bioreactors. But in the case of the new Ebola treatment ZMapp, developed by Mapp Pharmaceuticals, the antibodies were produced in tobacco plants at Kentucky Bioprocessing, a unit of tobacco giant Reynolds American.

The tobacco-plant-produced monoclonals have been dubbed "plantibodies."

What Is ZMapp? Could It Be A Cure For Ebola?
"Tobacco makes for a good vehicle to express the antibodies because it is inexpensive and it can produce a lot," said Erica Ollmann Saphire, a professor at The Scripps Research Institute and a prominent researcher in viral hemorrhagic fever diseases like Ebola. "It is grown in a greenhouse and you can manufacture kilograms of the materials. It is much less expensive than cell culture."

In the standard method of genetic engineering, DNA is slipped into bacteria, and the microbes produce a protein that can be used to combat a disease.

A competing approach called molecular "pharming" uses a plant instead of bacteria. In the case of the Ebola treatment, Mapp uses the common tobacco plant, Nicotiana benthanmianas.

The process is very similar. A gene is inserted into a virus that is then used to infect the tobacco plant. The virus acts like a micro-Trojan Horse, ferrying the engineered DNA into the plant.

Cells infected with the virus and the gene it is carrying produce the target protein. The tobacco leaves are then harvested and processed to extract the protein, which is purified.

ZMapp's protein is a monoclonal antibody, which resembles ordinary disease-fighting antibodies but has a highly specific affinity for particular cells, including viruses such as Ebola. It attaches itself to the virus cells and inactivates them.

APPROVAL PROCESS

The drug so far has only been produced in very small quantities, but interest in it is stoking debate over whether it should be made more widely available to the hundreds of people stricken with Ebola in Africa while it remains untested.

"We want to have a huge impact on the Ebola outbreak," Mapp CEO Kevin Whaley said in an interview at company headquarters in San Diego. "We would love to play a bigger role."

Whaley said he was not aware of any significant safety issues with the serum. He would not discuss whether the company has been contacted about providing the drug overseas.

But he did note the novel manufacturing process carries its own risk, and would have to be cleared by the U.S. Food and Drug Administration as part of the approval process.

The FDA would, for example, have to be satisfied that the plant extraction process had not led to contamination of the resulting drug.

The tobacco plant grows quickly, said Reynolds spokesman David Howard, and "it takes only about a week (after the genes are introduced) before you can begin extracting the protein."

He declined to say how much medication each plant can yield or whether Kentucky Bioprocessing is in a position to produce ZMapp in significant quantities.

Scripps' Saphire said it can still take anywhere from one to three months to produce the ZMapp serum for wider use given the complexities of the process.

PENTAGON FUNDING

In 2007, Kentucky Bioprocessing entered into an agreement with Mapp Biopharmaceutical and the Biodesign Institute of Arizona State University to refine the tobacco-plant approach. The approach attracted funding support from the Pentagon's Defense Advanced Research Projects Agency (DARPA).

For all the hope, however, the plant technique has delivered few commercial products. In 2012 the FDA okayed a drug for the rare genetic disorder Gaucher disease from Israel's Protalix BioTherapeutics and Pfizer. Called Elelyso, it is made in carrot cells, and is the only such drug to reach the market.

Other companies have fallen far short, though it is not clear if the technique was to blame. Calgary-based SemBioSys Genetics Inc, which used safflowers to produce an experimental diabetes drug, folded in 2012 before it finished clinical trials.

Even Kentucky Bioprocessing, which at one point was developing monoclonal antibodies against HIV (the virus that causes AIDS), C. difficile bacterial infection, and the human papillomavirus, has dropped the last two projects, Howard said.

Last year Mitsubishi Tanabe Pharma Corp acquired a majority share of Quebec City-based Medicago, which is developing influenza and other vaccines using the tobacco-plant technology. The other 40 percent is owned by tobacco giant Philip Morris International.

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