The world’s first plant-based livestock vaccine (for Newcastle disease in poultry) was approved in 2006 in the US. Now, there is one for Classical Swine Fever (CSF, also known as hog cholera) in pigs.
Because of the advantages that plant-based have in comparison to other types of vaccines, more of them for pigs and other livestock may be coming. The production of plant-based vaccines falls under what is known as “biopharming” or “plant molecular farming,” where genetically modified plants are used to produce a wide range of pharmaceuticals and industrial products.
“Early work on plant-based pharmaceuticals focused on using food crops such as corn and rice to hopefully develop a cheap, efficient way to deliver vaccines,” explains Dr Donald Stewart, CEO of the Canadian plant-based biopharmaceutical company PlantForm Corporation. “However, progress in this area slowed around 2002 due to concerns about cross contamination of other field crops.”
Non-food crops like tobacco then came into the spotlight. Tobacco is a very suitable plant for biopharming, with fast growth and genetics that are well understood. Over many years, tobacco plants have been genetically engineered to produce therapeutic proteins, monoclonal antibodies and vaccines to treat cancer, inflammatory diseases and other conditions. Other plants used in biopharming include duckweed, moss and alfalfa.
Compared to other culturing systems for biological drugs, plant-based systems are cheaper, faster and larger in capacity, with unlimited scale-up. They also offer a lower risk of contamination from animal and/or human pathogens, and can produce novel and complex molecules that cannot yet be produced with animal cell cultures. Novel plant-based pharmaceuticals follow the same regulatory approval processes as other biologic (large molecule) protein drugs.
Dr Stewart explains that there are 2 main ways to genetically modify plants to turn them into “mini-factories” for drug production: through a process called “transient expression” or by developing lines of ‘stable transgenic’ plants.
“With transient expression methods, plant leaf material is infiltrated with an Agrobacterium suspension that contains the genetic material for the target therapeutic protein or antibody,” Dr Stewart explains. “This involves immersing fully-grown plants in the suspension under vacuum pressure, which enables the Agrobacterium to penetrate the plant cells to introduce the genes of interest, see Figure 1. The plant’s DNA is changed so that the desired protein is produced. The plants continue to grow for another week or so, then they are harvested and the protein is extracted and purified to make a biopharmaceutical drug.”
PlantForm’s ‘VivoXpress’ system is a transient expression method. It was developed by Dr J. Christopher Hall, retired founder of PlantForm and former Canada research chair in recombinant antibody technology at the University of Guelph in Ontario. PlantForm was established in 2008 using a strain of tobacco.
The other method is stable transgenic plant lines, developed by stably altering the DNA of a plant’s nuclear or chloroplast genomes. Seed lines are then developed for continual propagation of plant biomass using traditional agricultural techniques and equipment. However, it takes time to generate and select for the desired seed lines. Furthermore, stable transgenic (nuclear-transformed) plants typically produce lower yields of recombinant proteins compared to transient expression systems.
As those in the pig industry are well aware, CSF is a highly-contagious viral disease that affects both domestic pigs and wild boar, causing severe illness and death in millions of swine each year around the world.
In 2019, Bioapp in South Korea developed the world’s first plant-based CSF vaccine, called Herbavac CSF Green Marker. It was originally developed at Pohang University (Postech) in South Korea by a team led by Dr Eun Ju Sohn, whom Dr Stewart calls the world’s leading specialist in plant-based vaccines for animal health. BioApp also has a large state-of-the-art manufacturing facility in South Korea.
In October 2021, Posco (a large commodities trading company and a major investor in Bioapp) signed an agreement with PlantForm to bring Herbavac to markets in North America, Brazil and Argentina. Registration is expected to be complete in the US and Canada within about a year, says Stewart, and in South America, in 1 to 2 years.
There are several CSF vaccines already available in different world markets, all of them “live vaccines.” Live vaccines use a weakened (or attenuated) form of a pathogen like a virus. Because these vaccines are so similar to the infectious agent they help prevent, they create a strong and long-lasting immune response.
In comparison, Herbavac provides strong immunity but also, says Dr Stewart, provides the importantly capacity for easy differentiation of field infection from vaccinated animals. That is a unique characteristic of this vaccine, he explains, which allows veterinarians, scientists and others to determine whether an antibody reaction in a pig is from natural sources (including a live vaccine) or from vaccination with Herbavac. Storage requirements (2-8°C) and expiry (18 to 24 months) are at least as good as competing products.
Plant-based CSF vaccines are also allowed to be used in CSF-free countries such as the US, Canada and some European countries.