Plant-based production will play a key role in the fight against COVID-19 and its variants as developers embrace low-cost alternatives to traditional manufacturing methods.

Efforts to create countermeasures against the SARS-CoV-2 virus were already underway when the WHO declared a pandemic in March 2020. As development of vaccines and therapies progressed, work began to ensure there was sufficient production capacity.

Since then, efforts to further increase capacity and make long-term, large-scale production cheaper have intensified, says Jay Xu, PhD, from the Arkansas Biosciences Institute, with plant-based systems emerging as a front runner.

“Plant-based production of anti-COVID-19 therapeutics is a promising approach that offers several advantages over current production methods. It has the potential to provide a safe, cost-effective, and scalable solution for producing the treatments.”

Xu, who looked at plant-based expression systems in a new study, says speed and flexibility are among the potential advantages.

“Plant-based production, particularly transient expression systems, could prompt rapid—4–8 weeks—manufacturing of target biologics on a large scale, which meet emergency demands, such as in the case of the COVID-19 pandemic.

“In addition, plant-based production can be used to produce a wide range of therapeutics, including monoclonal antibodies, vaccines, and other protein-based treatments. This versatility makes it a valuable tool for responding to emerging diseases like COVID-19.”

Plant-made pipeline

Several manufacturers are already using plants to make products with Medicago’s COVID-19 vaccine Covifenz—which consists of virus-like particles (VLPs) produced by a genetically modified species of tobacco called Nicotiana benthamiana—being the highest profile.

In addition, Kentucky Bioprocessing is developing a COVID-19 vaccine called KBP-201 that includes an antigen made in a plant-based expression system and iBio has several candidate plant-made jabs in development.

And beyond vaccines, there are other plant-made COVID-19 countermeasures in the pipeline according to Xu, who cites a novel antiviral chewing gum being developed by Henry Daniell, PhD, and colleagues at the University of Pennsylvania as an example.

“This virus-trapping gum contains plant-made CTB-ACE2, which is ACE2 fused with non-toxic cholera toxin subunit B (CTB). CTB-ACE2 is made in chloroplasts of transgenic lettuce. The lettuce was then powdered and blended with cinnamon-flavored chewing gum.

“In effect, the gum is designed to trap and neutralize SARS-CoV-2 in the saliva and, ideally, diminish the amount of virus left in the mouth,” Xu says.

Initial investment

The only potential hurdle for wider use of plant-based manufacturing is the extensive infrastructure required. However, Xu says, any investment in the growth, transformation, culture and processing systems that are needed would be quickly recouped.

“Plant-based production can be less expensive than culture-based production methods. While the initial investment in infrastructure for plant-based production can be high, once the plants are established, they can be propagated using relatively low-cost methods. In contrast, culture-based production methods can be more expensive due to the cost of media, equipment, and facilities required to maintain the culture, which can add to the cost of producing therapeutic proteins.

“Overall, plant-based production of anti-COVID-19 therapeutics offers several advantages over culture-based production in terms of cost and ease of scale-up. While there are challenges to implementing this production method, such as the need for specialized infrastructure and expertise, the potential benefits make it a promising approach for meeting the demand for COVID-19 therapeutics.”

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