Molecular farming is an easy, fast and safe method for producing vaccines and therapeutic proteins in plants, and now, a team of researchers has developed a good manufacturing practices-compliant pilot factory.
The vaccine shortage during the H1N1 influenza pandemic in 2009 showed that although producing vaccines using chicken eggs is a reliable method, in a global emergency, the process takes too long and does not yield enough vaccine.
What is needed are alternative methods with shorter production times and larger capacities, such as the production of vaccines and therapeutic agents in plants.
In molecular farming, as this method is known, genetic information needed for target protein production is introduced into the plant via virus vectors that are harmless to people. Moreover, plants have protein synthesis machinery similar to that of people and can accommodate complex proteins.
After decades of being called a health menace, the tobacco plant is about to become a source of potentially lifesaving medicines, based on a collaboration led by Andre Sharon, a professor of mechanical engineering at Boston University's College of Engineering and director of the university's Fraunhofer USA Center for Manufacturing Innovation (CMI).
Sharon's team built a fully automated factory that uses synthetically altered tobacco plants to grow vaccines for some of the world's deadliest viruses, including H1N1 influenza, yellow fever and malaria, as well as for emerging biological threats.
"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," said Vidadi Yusibov from the Fraunhofer Center for Molecular Biotechnology (CMB).
CMI and CMB joined forces in 2010 to build the plant-based factory in Newark, Del.
Typically, flu vaccines have been produced in chicken eggs using a process that Sharon said is "expensive and perilously slow" in the case of epidemics.
In 2009, in response to the H1N1 pandemic, the U.S. government began a $1.6 billion program to find ways to quickly produce a large number of vaccine doses. The next year, the government's Defense Advanced Research Projects Agency learned of the CMI/CMB research to produce proteins within the leaves and stalks of tobacco plants and awarded the group a grant to study the rapid production of vaccines.
The Delaware factory now grows tens of thousands of tobacco plants, which are tended by robots that bring the trays to and from lighted, irrigated growth modules. After four to six weeks of growth, the robots move the plants to a machine that inserts genetic instructions to produce the appropriate protein. One or two weeks later, a harvesting machine shears the plants from their trays and uses routine chemical separation procedures to extract the protein, which is converted to a vaccine.
"This factory turned what would be an agricultural process — where you would have to seed the plants and give them the right (amount of) light — into an industrial process where you grow the plants hydroponically in trays, meaning they are not grown in soil," Sharon said. "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."
The pilot facility is capable of producing up to 300 kg of biomass a month, which roughly corresponds to 2.5 million units of vaccine, an announcement said.
CMI, a collaborative center between Boston Univeristy and Fraunhofer Gesellschaft, was established in 1995. The center scales up promising research into real automation systems, laboratory procedures, instruments and devices that are often deployed to the marketplace.
Fraunhofer Gesellschaft is Europe's largest applied research organization, with 66 branches worldwide and eight in the U.S.