In tech to make Ebola vaccine, Israeli firm was there first

Tobacco plants may be key to treating the dread disease – and Israel’s CollPlant knows more about ‘tobacco treatments’ than anyone

A CollPlant tobacco hothouse, used for 'growing' human collagen. Collplant's technology was developed at Hebrew University and commercialized by Yissum (Photo credit: Courtesy)
A CollPlant tobacco hothouse, used for 'growing' human collagen. Collplant's technology was developed at Hebrew University and commercialized by Yissum (Photo credit: Courtesy)

Scientists around the world scrambling to find a treatment for Ebola are looking to the tobacco plant for assistance, as a vehicle to synthesize antibodies for a vaccine. And that means they are likely to be looking towards Israel’s CollPlant, a company that is a pioneer in the development of recombinant proteins using tobacco plants.

While CollPlant is not involved with the development of Zmapp, the tobacco-synthesized “cocktail” being developed by several American companies that, so far, is the only Ebola treatment on the horizon, the Israeli company knows a great deal about large-scale production of human cells in tobacco plants, said Prof. Oded Shoseyov, founder and chief scientific officer of CollPlant. “We were the first company in the world to use tobacco plants to do large-scale manufacturing of human proteins, and to receive EU permission to market tobacco-synthesized human elements,” he told The Times of Israel in an interview.

Zmapp, according to its inventors, San Diego-based Leaf Bio and Mapp Biopharmaceutical, with assistance from Defyrus Inc. of Toronto, the US government and the Public Health Agency of Canada, “is composed of three humanized monoclonal antibodies manufactured in plants, specifically Nicotiana. It is an optimized cocktail combining the best components of” three antibodies. The antibodies bind to proteins on the Ebola virus, which triggers the immune system and destroys the germ.

Zmapp, according to its makers, was first identified as a possible treatment last January. It has since been used on several Ebola victims in Liberia, with mixed results. It has been administered to about half a dozen patients, with most surviving. Although tests on animals have shown positive results, Zmapp has not been tested clinically on humans.

Nevertheless, Zmapp is the world’s best bet for an Ebola treatment, at least right now. The problem is, there are not enough doses to conduct clinical trials – or to treat patients, for that matter. Production is being handled by a company called Kentucky Bioprocessing (KBP), which has been using tobacco plants to synthesize Zmapp. Tobacco plants are injected with Ebola virus and fused with genes for a natural tobacco virus. The plant then responds, producing antibodies to fight the virus. The antibodies are extracted and injected in Ebola victims, hopefully curing them.

It was CollPlant that pioneered the mass production of human materials in tobacco plants. “We didn’t invent the method, but we have taken it farther than anyone else,” said Shoseyov. Using nanotechnology, CollPlant produces human collagen from tobacco plants, a far better way to produce an element essential to repairing bones and joints than the alternatives – using materials extracted from cows and pigs to produce artificial collagen.

Prof. Oded Shoseyov (Photo credit: Courtesy)
Prof. Oded Shoseyov (Photo credit: Courtesy)

Collagen is a key component of the body, playing a major role in connective tissue and used by the body to repair broken bones and joints. When a splint is applied to a broken bone and the two separated parts of the bone are joined, the body will usually produce enough collagen to complete the repair process. However, if part of the bone is missing, the body will be unable to replace or repair it. In those cases, artificial collagen can be applied to the break, with a scaffold holding the elements in place, allowing the body to use the inserted collagen to make the repair.

Artificial collagen made from pigs and cows is common but not ideal. An alternative is harvesting of human collagen from corpses. Human collagen from the dead is more effective for the body, but collagen can be harvested only from donors, so supplies are limited.

CollPlant’s solution allows the production of real human collagen – producing material that can be most efficiently used by the human body – without the need to rely on the dead. CollPlant’s technology inserts human collagen into tobacco plants that are raised in hothouses, ensuring that they remain isolated from the food chain. The bio-engineered plants mimic the natural synthesis of authentic human protein and produces Procollagen, the natural precursor of collagen. The Procollagen collected from the plants and is processed into CollPlant’s artificial collagen product.

“Tobacco has a big biomass, and it grows quickly; you can grow a six-foot-tall plant in under two months,” said CollPlant CEO Yehiel Tal. “The production process is easy to control using our technology. We know how much collagen there is in the leaves produced by the plants, and can regulate its strength. And tobacco leaves are big, so they hold lots of collagen.”

CollPlant, which has been in business for about six years, is also the most experienced company in the world at producing large amounts of complex human materials in tobacco plants, said Shoseyov. “There are several companies, for example, developing ways to produce insulin in tobacco plants, but insulin is just a single protein. Collagen is much more complicated. To produce it you have to synthesize five human genes, a very difficult feat. I don’t know of any other company that can do this.”

As such, CollPlant is ready and able to help out the makers of Zmapp, or anyone else, who might seek assistance in the production process. Not that they need any help, said Shoseyov. “We know them very well, and they know what they are doing. We have been in touch with them on a regular basis; the community of researchers doing work in this area is very small.”

CollPlant’s experience in this area is likely to become an important resource in many areas of medical treatment. Production of collagen, antibodies, proteins, and other human material via plants – especially tobacco plants – is the wave of the future, said Shoseyov.

“The investment numbers make so much more sense, both in development – the ‘upstream’ – and testing and production – the ‘downstream,’” he said. “Currently, manufacturers have to set up clean rooms with all sorts of gear and equipment, at a cost of as much as $100 million, in order to develop new cures. In addition, these facilities require all sorts of government licenses and authorizations, so the process between the beginning of research and production could take as long as five years. Setting up a greenhouse for experimental medicine costs about a half million dollars, and requires a lot less government oversight,” he said.

“In addition, researchers working on a treatment don’t have to be as careful with procedures to prevent germs and viruses from spreading – because plants do not harbor human pathogens. The research process can be relaxed, with researchers putting more of their attention into solving problems. More researchers and companies are looking at these methods to develop treatments of all kinds, and that, I believe, will benefit everyone,” Shoseyov added.

If there was one piece of advice Shoseyov has for the Zmapp makers, it’s this: “Just do it. The methods of production are as simple as raising tomatoes and lettuce – and the world is waiting for this.”

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