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.

Efficient way to deliver vaccines

“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

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.

How plants are used to make 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.

Stable transgenic plant lines

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.

CSF: A contagious viral disease

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.

Bringing plant-based CSF vaccine to the Americas

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.

Easy differentiation of field infection

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.

PigProgress | Treena Hein | December 15, 

Tail biting continues to be a major health and welfare challenge in commercial pig production with diet being a major risk factor. Researchers from Denmark have studied the link between a pig’s diet, gut health and mood, and have uncovered some interesting results.

The feeding factor

This study looked closely at the diet and suggests that diet-related risk factors for tail biting are under- and oversupply of protein (including tryptophan), lack of satiation, fine feed particle size, low dietary fibre content and a limited number of feeder spaces.

These factors can cause social stress, gastric ulcers, dysbiosis of the gut microbiota, disruption of the intestinal epithelium, and affect the animal’s stress sensitivity via the microbiota-gut-brain axis, which can cumulatively lead to tail biting.

Protein and amino acid imbalances

The Danish researchers note that feeding diets with too low dietary protein levels, an imbalance in essential amino acid composition and/or mineral deficiency may increase the occurrence of damaging behaviours such as ear biting and tail biting.

Being protein deficient impairs the pig’s resilience to cope with stressors and predisposes behavioural depression signs and aggression and increase foraging motivation, which increases the risk of tail biting via increased exploratory motivation and tail-mouth behaviour. Meanwhile, an oversupply may increase anxiety behaviour.

Furthermore, mineral deficiency may increase attraction to blood (due to blood’s content of protein and several minerals), accelerating a tail-biting outbreak when skin has been broken.

The research team believes that adequate amino acid levels including tryptophan, and the inclusion of certain dietary fibres in the diet exceeding levels in standard diets, may stimulate the establishment of beneficial gut microbiota (e.g., microbial diversity and short-chain fatty acid-producing bacteria) that protect against inflammation and increase stress resilience.

Optimal levels of tryptophan

Tryptophan is a precursor of serotonin, which is an important neurotransmitter involved in many processes including mood, stress sensitivity, regulation of gut motility, appetite, immune function, sleep and memory. Tryptophan metabolism is modulated by gut microbiota, and an excess of tryptophan can also be metabolised into potentially harmful substances. So, the researchers note that careful consideration is needed in future studies investigating whether the optimal tryptophan level for gut and mental health differ from levels for optimal growth.

The role of antibiotics

Antibiotics are a useful and necessary tool to combat specific bacteria that pose a risk of tail biting, but antibiotics can also disturb the gut microbial balance, which in turn increases the risk of tail biting.

Conclusion and considerations

In conclusion, while tail biting is multifactorial, the researchers suggest that an imbalance in the microbiota-gut-brain axis, modulated via the diet, should be considered as a pathway for the development of tail biting, but needs more research. The team, led by Cecilie Kobek-Kjeldager, suggests a whole-animal approach, including considerations on gut health, satiety, a beneficial gut microbiota and an adequate feed supply avoiding social stress to mitigate tail biting.

PigProgress | Natalie Berkhout | December 13,