VACCINE MACHINE: The pods are self-contained clean rooms that have either HEPA or ULPA filtration. They require only an electrical hookup and chilled water from the outside. Standard modules are 5.5 by 13 meters and provide a 5.5- by 7.6-meter working environment, gown dressing areas and a separate mechanical support area. Modules provide 2.4 to 5.5 meters of height depending on the need. Image: © THE TEXAS A&M UNIVERSITY SYSTEM
The H1N1 virus's rapid spread worldwide last year exposed the weaknesses in the global system for swiftly developing, manufacturing and distributing vaccines for newly identified strains of influenza. In Texas, researchers are attacking the first two of these problems through Project GreenVax, which will use a plant-based approach to vaccine development and a modular manufacturing environment that can scale quickly as vaccine demand grows.
Project GreenVax is led by the Texas Plant-Expressed Vaccine Consortium, a joint venture of The Texas A&M University System and pharmaceutical facility technology maker G-Con, LLC, both located in College Station, Texas. The consortium is investing $21 million in GreenVax to go along with the $40 million in funding from the Defense Advanced Research Projects Agency (DARPA).
In the course of just seven months last year the spread of H1N1 influenza worsened from an outbreak specific to Mexico and the United States to a global pandemic and U.S. national emergency. The World Health Organization (WHO) reported that, by the end of the year, H1N1 was responsible for more than 12,200 deaths and had turned up in 208 countries. Although the first cases were reported in April, the first vaccine doses did not start shipping until October.
The WHO's Strategic Advisory Group of Experts (SAGE) on immunization projected in October that it would take the world's labs 12 months to produce about three billion doses of H1N1 vaccine. GreenVax's initial test run is expected to produce 10 million doses of H1N1 vaccine in 12 months using tobacco plants to develop the antibodies. If successful, the researchers say their facility alone could be scaled up to produce 100 million vaccine doses per month.
Breaking a few eggs
Most of the H1N1 vaccines were produced using chicken eggs. Scientists crack the shell and inject the influenza virus into the fluid surrounding the embryo. Ideally, the embryo is infected and the virus multiplies. After several days of incubation the eggs are opened and the virus is removed, purified and used to make the vaccine. It takes about two weeks to produce a flu vaccine using an egg, and the yield is not very high. In order to produce 300 million doses of a vaccine, egg-based production would require some 900 million eggs, according to the U.S. Department of Health and Human Services.
In the plant-based approach, scientists instead infect a plant's leaves with a virus and then grind them up and separate out the antigens produced. Plants offer several potential advantages, says Ted Ross, an associate professor of microbiology and molecular genetics at the University of Pittsburgh's Center for Vaccine Research (CVR). They can be grown quickly and cheaply and have the potential to produce more vaccine per plant than is possible per egg, he says. Still, despite more than a decade of experimentation, he adds, "I don't know of any approved vaccines made using the plant-based approach."
Plants can be very good biofactories, says B. Brett Finlay, a biochemistry and molecular biology professor at the University of British Columbia in Vancouver. However, one problem is that proteins cultivated in plants might be different than those cultivated in animal cells (or a chicken embryo) and not necessarily effective in humans, he adds. "Also, standard FDA rules for plant product use in humans are not as well worked out."
Facilitating the plan
To support its work, GreenVax will begin construction next week on a new 13,500 square-meter biotherapeutic production facility. The facility is essentially a "tilt-wall" warehouse—built using precast concrete walls—that can be constructed in eight weeks, says Brett Giroir, vice chancellor for research for the A&M System and executive director of the university's Institute for Innovative Therapeutics (IIT).