When a future pandemic breaks out, public health officials may have a high-production vaccine factory at their disposal thanks to the work of Boston University researchers and engineers at the Fraunhofer USA Center for Manufacturing Innovation at Boston University. In conjunction with the Fraunhofer USA Center for Molecular Biology in Delaware and the biopharmaceutical company iBio, Inc., they have developed a fully automated “factory” that uses tobacco plants to efficiently produce large quantities of biological medicines within weeks.
This first-of-a-kind, plant-based vaccine factory takes advantage of the tobacco plant’s well-understood, genetically engineered mechanisms for producing specific proteins within the leaves and stalks. The factory consists of a series of robotically tended machines that plant seeds, nurture the growing plants, insert genetic instructions on what to produce, and harvest the plants at maturity.
“What was needed was a way to produce large doses of vaccines or other medicines, and the only way to do that is to treat it like an industrial process,” said Andre Sharon, a professor of mechanical engineering at Boston University and director of the Fraunhofer Center at BU. “Even though the process of making vaccines from plants is almost like farming – growing, watering, harvesting – we treat it like an automated manufacturing process. That’s how we can cost effectively scale it up from a few milligrams in laboratory demonstrations to many kilograms in case of a pandemic.”
“This is a perfect example of coupling engineering expertise and scientific advancement to cost-effectively meet a societal need,” said Boston University President Robert A. Brown, himself an engineer. “It is a model for collaboration that we strongly believe in on our campus, as they do at Fraunhofer as well.”
The unique plant-based vaccine factory resulted from a three-year collaboration between the College of Engineering, iBio, and the Boston and Delaware branches of Fraunhofer-Gesellschaft, Europe’s largest applied research organization.
“Everything was designed from the ground up. It’s all unique. These robots and machines were very difficult to design to have all the necessary capabilities,” said Sharon. “The process is faster, less expensive, safer, and does not require the sophisticated biological processing necessary in the more common vaccine production processes involving mammalian cells, animals, eggs, or bacterial cultures. So, theoretically you could put one of these factories in Third World countries or right in the middle of a big city, wherever it’s needed.”
The factory was designed to be time, cost and space efficient. It has the capacity to grow tens of thousands of plants in one batch. The plants are grown in multi-plant trays that are used to handle and transport the plants to the different processing stations. To automate the agriculture, two robots glide up and down narrow aisles, tending the plants – delivering trays to and from the lighted, irrigated growth modules to each processing station at the appropriate time.
Traditional methods of vaccine production take many months, but this process, from seeding to harvesting, takes just a few weeks. Once plants have reached a certain stage of growth, formulating large doses of vaccines could be produced very quickly.
Using preprogrammed robots eliminates the need for human contact, preventing potential contamination of the process and economizing the operation. One of the most daunting engineering challenges was developing a seeding machine to dexterously handle tobacco seeds, which are smaller and lighter than poppy seeds. The seeding station had to be designed to separate, pick up and plant a single seed into an array pattern on the growth tray.
After seeding and several weeks of growing, the robots shepherd trays of plants to a machine that biologically inserts instructions to produce the appropriate protein. The team developed a proprietary procedure that allows this procedure to be done cost effectively in bulk. After growing for several more weeks, a harvesting machine shears the plants from their trays, and using routine chemical separation procedures, the protein is extracted.