Whitney Palmer

Healthy turnabout for tobacco

Published in the Jan. 17, 2011, Raleigh News & Observer and the Jan. 17, 2011, Charlotte Observer

BY WHITNEY L.J. HOWELL – CORRESPONDENT

RESEARCH TRIANGLE PARK — For generations, tobacco served as North Carolina’s economic engine, creating wealth while also eroding public health.

Now, thanks to an international vaccine company setting up shop in Research Triangle Park, the cash crop could be turning over a new leaf to become an integral part of preserving good health.

A Montreal-based biotechnology firm, Medicago, uses the Australian tobacco strain Nicotiana benthamiana to manufacture H1N1 flu vaccines.

The process takes days and produces larger amounts of vaccine than the traditional months-long method of cultivating the virus in fertilized chicken eggs.

“With this technique, we’re not using the actual virus to produce the vaccine,” said Frederic Ors,

Medicago’s vice president of business development. “That’s the big difference from the egg-based vaccine method where you actually infect the eggs with the live influenza virus.”

 

Medicago uses the Australian tobacco strain, which is not used in cigarettes, because its delicate leaves are highly susceptible and receptive to pathogen infections, Ors said.

The plant also produces a purer vaccine because it does not inject its own DNA into the virus reproduction process. The vaccine is in the second phase of human clinical trials, and the company is currently enrolling volunteers to test it.

The company received a $21 million grant from the Defense Advanced Research Projects Agency in the U.S. Department of Defense to build a 90,000-square-foot facility in RTP, and it aims to produce 10 million vaccine doses per month.

Medicago selected RTP because of its long-standing expertise in high-tech innovation, Ors said.

Medicago broke ground in August and plans to begin large-scale manufacturing next fall. The $42-million plant will be the company’s North American site.

Breaking tobacco tradition

North Carolina traditionally produces tobaccos for use in cigarettes. As of 2009, according to the N.C. Department of Agriculture and Consumer Services, tobacco was still the state’s No.1 cash crop with more than 4,100 pounds produced and an economic impact of more than $7 billion.

Researchers are seeking more beneficial uses of tobacco’s well-mapped and easily modified genome, said Sandy Stewart, a tobacco specialist and crop science assistant professor at N.C. State University. In recent years, the crop has become popular in small-scale pharmaceutical research, and the textile industry is exploring ways to use the fibers to weave and spin thread.

Flu vaccines would be a novel and helpful use, especially if the tobacco approach speeds the drug’s production.

The emergence of the H1N1 flu strain in 2009 after the flu vaccine supply had already been produced highlighted the need for a faster way to create the inoculations.

Vaccine manufacturers use an 80-year-old technology, cultivating the virus in chicken eggs to produce the majority of flu shots each year. The process takes at least six months and uses millions of eggs.

Tobacco offers benefits

According to Ors, using the tobacco plant is beneficial not only because it reduces the risk of allergic reactions, but it also cuts production time to slightly more than two weeks.

“Our method is a very fast technique – faster than even the new cell culture technology to create vaccines,” he said. “The cell culture process takes roughly three months.”

 

To make flu vaccine, Medicago gets the DNA sequence of the latest flu strain from the World Health Organization’s website.

 

Instead of using the active virus, the company synthesizes the genetic sequence and creates viruslike particles. VLPs resemble viruses with a protein shell, and they are covered with protein strands specific to the disease the vaccine targets.

A VLP contains no infectious material, so it cannot cause illness even though the human body recognizes it as a real virus.

When making the vaccine, Medicago scientists dip mature tobacco leaves into a solution made with agrobacterium, an organism that easily transfers DNA between itself and plants. The genetically modified bacterium, widely used in biotechnology for two decades, moves into the plant’s cells without transferring its own DNA material and compromising the VLP’s purity.

The leaves remain in solution for two minutes under a vacuum, suctioning the bacteria particles to the plant cells. When the vacuum releases, the leaves soak up the particles, pulling the virus protein into the plant cells for replication, Ors said.

The plants incubate in a greenhouse for four to six days, producing a large amount of VLP in the leaves only. The leaves are then harvested by hand to ensure that no plant stem goes through the purification process, and they are shredded, said Mike Wanner, general manager of Medicago’s RTP facility.

The leaves go through a low-speed centrifuge several times to spin out and separate parts of the plant not intended for use.

“Roughly 99 percent of the leaf is garbage, so we have to isolate the viruslike particles from everything else,” Wanner said, adding that the refuse is safely discarded. “We remove the junk by using a centrifuge and a sterile filtration step. The result is a viruslike particle that is 98 percent pure. That’s as good as or even better than the current vaccines produced.”

Taking it slow

Although manufacturing flu vaccine with tobacco plants could have many benefits, completed vaccine should be introduced to the public on a small scale, said David Weber, a professor in the infectious diseases division at UNC-Chapel Hill School of Medicine.

“It may well turn out that using tobacco plants allows us to generate large amounts of flu vaccine and that purifying the vaccines is easier this way,” he said. “But we don’t know the risks. We know that tobacco isn’t good for you if you smoke it, so there’s a need to ensure a minimal carryover of tobacco into the vaccine.”

But Weber said the positive effect could be felt outside the public health arena. Not only would tobacco farmers benefit from having another use and market for their product, but tobacco-manufactured vaccines could also help fight hunger.

“Currently, 15 percent of the world’s egg supply is used to make vaccines,” Weber said. “Taking them out of the vaccine production process would free up a lot of eggs that can be used to feed people.”

To read the Raleigh News & Observer story online: http://www.newsobserver.com/2011/01/17/924832/healthy-turnabout-for-tobacco.html

To read the Charlotte Observer story online: http://www.charlotteobserver.com/2011/01/16/1985795/healthy-turnabout-for-tobacco.html

 

January 17, 2011 - Posted by wjpalmer | Healthcare, Science | agrobacterium, alternative uses for tobacco, amount of eggs eaten world wide, creating purer vaccines, David Weber, Defense Advanced Research Projects Agency, faster vaccine production methods, flu vaccine production with chicken eggs, Frederic Ors, H1N1 flu vaccines, Medicago, Nicotiana benthamiana, No. 1 cash crop in North Carolina, North Carolina State University, North Carolina tobacco industry, Sandy Stewart, tobacco genome, University of North Carolina at Chapel Hill School of Medicine, use of tobacco in pharmaceutical industry, use of tobacco in textile industry, using tobacco DNA to create flu vaccine, using tobacco for flu vaccines, using tobacco to make fabrics, vaccine facilities in North Carolina, vaccine innovation, vaccine production methods without allergic risk, virus-like particles, VLPs