Plant-based vaccines eliminate the need for bioreactors because they themselves are the bioreactors. Plants can be grown in climate-controlled, pharmaceutical-grade greenhouses that keep out bugs and pests but do not require sterile conditions. In Medicago’s greenhouse in Raleigh, North Carolina, two mechanical arms pick up a steel tray of 126 juvenile Nicotiana Bentham plants, a weedy, Australian cousin of the tobacco plant used in cigarette products. The tray of plants is swiftly turned upside down and dunked into a metal basin of liquid containing millions of agrobacteria, a group of bacteria that naturally infect plants. The agrobacteria in this greenhouse are altered to contain a small piece of DNA from the influenza or COVID-19 virus. While the plants are submerged, a small vacuum sucks at the plant’s roots causing the leaves to collapse and shrivel up.
A few seconds later, the vacuum is released, causing the leaves to re-expand and, like a sponge, soak up the liquid carrying the agrobacteria, which spread throughout the entire vascular structure of the plant. In a matter of minutes, the Nicotiana Benthamian plants have been transformed into mini bioreactors. The agrobacteria transfer the viral DNA to the plant cells, which then make millions of copies of virus-like particles that serve as antigens but are not infectious. “It’s totally cool. It’s one of the best things actually. It’s called agroinfiltration or vacuum infiltration,” says Medicago’s Brian Ward. The plants are resettled in the greenhouse and after five or six days, the leaves are harvested, placed on a conveyor belt, chopped into tiny pieces, and soaked in an enzyme bath that breaks down the hard plant cell wall and releases millions of virus-like particles, which are purified and packaged, Ward explains. The finished product is a plant-derived vaccine. In 2018, Medicago’s flu vaccine was the first in the world to complete phase three clinical trials. For conventional vaccines, once the virus or viral particles are extracted from the cells that grew them and purified, they must be kept cold. This includes Medicago’s plant-based flu and COVID-19 vaccines.
But other plant-based vaccines skirt this problem by skipping the purification step altogether. Genetically modified lettuce is also commonly used to make vaccines. According to Henry Daniel, a researcher at the University of Pennsylvania who has been involved in lettuce-based vaccine work, scientists use a gene gun to insert a slice of viral DNA into the genome of a lettuce seed’s chloroplast, the part of the plant where photosynthesis, the process in which a plant converts sunlight into usable energy, takes place. Chloroplasts carry about 100 copies of their genome—the genetic material that provides the cell with instructions to function and make copies of itself—unlike most other cells, which have only one copy. This means chloroplasts can produce up to 100 times the amount of target antigen. Once the viral gene has been inserted into the genome, the seed is grown under controlled but otherwise normal conditions at a farm or greenhouse and then harvested. But here, because lettuce is an edible plant, instead of purifying the virus-like particles by removing all the plant cells and debris, the chloroplasts containing the antigen are ground up into a powder that is then formulated into a pill or capsule, which would then be taken orally. Several lettuce-based vaccines for humans and animals are under development, but none have advanced to clinical trials. The advantage to a pill form of a vaccine is that it can be stored at room temperature for long periods, thus eliminating the cold chain problem Emerging plant-based vaccine technology will not only help the world respond to the current and future pandemics but also offers an opportunity to expand vaccine production to developing countries, according to Hefferon. Vaccines remain a cornerstone of public health, preventing some 4 to 5 million deaths each year. And yet many places around the world lack access to vaccines for measles, meningitis, and whooping cough. That means that some 1.5 million people a year still die from preventable infectious diseases.
Aishwarya Says:
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