Growing vaccines from seed

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\"OneTwo robots glide up and down narrow aisles in a unique factory, tending to and delivering plants to and from growth modules to processing stations.

A science fiction film about the future, where people can no longer produce enough food because of the ravages of nuclear war, overpopulation, or some other devastation? No, these robots work in a factory that manufactures medicine from plants.

The past century has seen outbreaks of various flu strains (Spanish, Asian, Hong Kong, avian, swine, and others), and creating vaccines as quickly as possible is crucial. Thanks to the work of Boston University researchers and engineers at the Fraunhofer USA Center for Manufacturing Innovation at Boston University, when a future pandemic breaks out, public health officials may have a high-production vaccine factory at their disposal. In conjunction with the Fraunhofer USA Center for Molecular Biology in Delaware and the biopharmaceutical company iBio, Inc., the researchers 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,” says Andre Sharon, a College of Engineering professor of mechanical engineering 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 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,” says 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 ENG, iBio, and the Boston and Delaware branches of Fraunhofer-Gesellschaft, Europe’s largest applied research organization.

The factory was designed to be time-, cost-, and space-efficient, and can grow tens of thousands of plants in one batch. The plants are grown in multiplant trays that are used to handle and transport them to the different processing stations. To automate the agriculture, robots care for the plants and bring 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 done very quickly.

After seeding—with a seeding machine designed to separate, pick up, and plant a single seed into an array pattern on the growth tray—and several weeks of growing, the preprogrammed 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 to be done economically 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.