Growing Vaccines

Earlier this week, a group of scientists working under contract with the U.S. Defense Advanced Research Projects Agency (DARPA) announced a breakthrough in high-yield vaccine production that may solve the problem of vaccine shortages during virus epidemics.

Dr. Vidadi Yusibov, a professor at the Delaware-based Fraunhofer USA Center for Molecular Biology, and Dr. Andre Sharon, a professor at the Center for Manufacturing Innovation at Boston University, led the development of a robotic tobacco farm in Newark, Delaware, that can "grow" vaccines on a massive scale.

Molecular farming, as this vaccine-production method is known, introduces the genetic information needed to produce a “target” protein into plants.

"We use tobacco plants because they multiply and maintain our virus vectors very well. In addition, they grow fast yielding, large quantities of biomass in a short period of time," Yusibov said in a press release.

Virus vectors are biological carriers containing genetic information that the tobacco plants absorb and turn into proteins naturally. The proteins are then harvested to make vaccines.

Yusibov explained that plants can be used to make vaccines to protect against any virus. “We naturally infect the plant with what we call ‘launch vectors’ containing multiple copies of very specific genetic molecules from the virus,” he told Healthline. “This process results in high plant yields of the precise proteins we need to make vaccines for specific diseases.”

A Way to Stop Deadly Epidemics

In the winter of 2009-2010, a devastating shortage of swine flu vaccine contributed to the H1N1 pandemic that took the lives of more than 150,000 people worldwide. In response, the federal government set aside $1.6 billion—the largest immunization program budget in U.S. history—to develop faster ways to produce large volumes of vaccines to combat deadly viruses.

According to DARPA, it can take more than seven years and hundreds of millions of dollars to produce one new antimicrobial drug or vaccination—in a process that cannot be replicated. DARPA’s goal is to leverage biology and engineering to enable on-demand production of vaccines in a way that can be safely, quickly, and inexpensively replicated.

Yusibov and Sharon won the DARPA contract and began collaborating on factory designs. “Once some initial difficulties in understanding were overcome, our teams of biologists and engineers succeeded in building our automated plant-based vaccine production factory,” Sharon said in a press release. “Now we have plants that consistently grow and make proteins to the same predictable quality, time after time, whenever and wherever we like."

Compared to conventional chicken-egg vaccine production methods, agricultural production means less contaminated waste at the end of the day. “Our plant production makes 10 percent of the waste that chicken-egg factories produce,” Yusibov said.

Even with the cost of high-capacity automation, he estimates that the infrastructure costs are 10 times less than those involved in other vaccine-growing methods. And they've found other ways to speed up production and cut costs.

“We have also reduced production time from nine months to one week after introducing a virus vector into mature plants,” said Yusibov. “For tobacco, the time from seed to mature plant is just four weeks,” he added.

How the Factory Process Works

The automated tobacco factory uses hydroponic growing methods and robots at every step of the process.

The plants are grown in trays with hydroponic cultures of nutrients and water in a base of mineral wool, rather than soil, and in specially designed growth modules.

Light, water, and nutrients are precisely meted out. Specially designed robots bring the plants from station to station to carry out the various steps—from planting the tiny seeds and introducing the virus vector to harvesting the plants and extracting the vaccine proteins.

The plants grow for four weeks before the virus vector is introduced by means of vacuum infiltration. To do this, a robot picks up a tray of plants, turns it upside down, and submerges the plants top down in water. This water holds the vector containing genetic information that tells the plants which protein to produce.

A vacuum is then created by drawing all the air away from the water and plants. “As soon as we switch off the vacuum, the plants suck in the water together with the vector. This takes just a few seconds," Sharon explained.

The plants are then put back into the growth module, and in about seven days they have produced the target proteins in their leaves and stalks. The plants are harvested, the leaves are cut into small pieces and liquified, and the proteins are extracted from the liquid.

The scientists now grow tens of thousands of tobacco plants in the Delaware factory. “This factory turned what would be an agricultural process—where you would have to seed the plants and give them the right light—into an industrial process,” Sharon said.

The pilot facility is capable of producing up to 300 kilograms of biomass a month, which corresponds to about 2.5 million units of vaccine. “These plant vaccine factories can be built anywhere in the world where a large number of vaccines are needed, whether it be urban, rural, or developing areas,” said Sharon.

Yusibov said it's also possible to adapt the process for human, rather than robotic, production to provide jobs for human workers. “They wouldn’t even need to be highly trained," he said. "But with robotics, the process is absolutely reliable."

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