Plants have emerged as an innovative platform for producing vaccines as they offer several advantages over traditional egg- or cell-based methods. Some of the key benefits of plant-based vaccine production include lower costs, faster scale-up, and enhanced stability and safety profiles.
History and Development of Plant-based Vaccines
Research into plant-based vaccine production began in the 1990s. Some early milestones included the expression of the first vaccine antigens in transgenic tobacco and potato plants in the mid-1990s. Since then, significant advancements have been made in developing plant-based expression systems and optimizing crop species for economical production. Tobacco, a non-food crop, was one of the first plants used but others like carrot, lettuce, and corn have now also been investigated.
In recent years, several plant-made vaccines have entered clinical trials, including those for diseases like influenza, hepatitis B, and Norwalk virus. In 2016, the first approval of a plant-based vaccine called NP321 was granted by the Canadian regulatory authorities for use against enterotoxigenic Escherichia coli (ETEC) bacterial infection in horses. This marked a landmark achievement for the field. Currently, a number of plant-based vaccines are in late-stage development for various human and animal indications.
Advantages of Using Plant Systems for Vaccine Production
There are multiple advantages of using plant expression systems over traditional egg- or cell-based methods for vaccine manufacturing.
Cost efficiency: Plants provide an economical platform for mass production of vaccines. They do not require expensive large-scale fermentation facilities and equipment. The low capital and operating costs make plant-made vaccines more affordable, particularly for developing countries.
Scalability: If needed, production can rapidly be scaled up by increasing the cultivated area within a short time frame, which is difficult with conventional methods.
Thermostability: Vaccines derived from plants do not require cold chain logistics and storage due to inherent thermostability of most plant-made antigens. This is a major advantage for tropical countries with limited cold storage infrastructure.
Safety: Plant viral expression vectors pose extremely low risk of contamination by human or animal pathogens. Further, plant cells do not harbor endotoxins and there is no risk of reversion to virulence as in some live attenuated vaccines.
Flexibility: Plants can be used to produce a wide variety of subunit vaccines, including those requiring post-translational modifications like glycosylation which may not be achievable using other systems. They present no religious or cultural barriers.
Technological Challenges and Strategies
While plant-based vaccines production platforms hold immense potential, certain technical challenges still need to be addressed. One major hurdle lies in achieving requisite levels of antigen expression in plant tissues. Strategies to improve recombinant protein yields include optimizing codon usage, choosing robust viral/plasmid vectors, and employing potent tissue-specific or seed-based promoters.
Purification of target antigens away from plant cell debris in economically viable processes is another difficulty area. New extraction and purification methods employing plant-derived molecular chaperones, fusion tags, and phase separation techniques are helping to resolve this issue. Proper antigen folding and assembly is essential for immunogenicity and can be enhanced by co-expressing chaperones or targeting the subunit to specific organelles. Choice of crop species and tissues influencing antigen stability and accumulation levels also require extensive evaluation.
Regulatory Compliance and Clinical Trials
To gain regulatory approval and market access, comprehensive agronomic, analytical, and clinical data on plant-made vaccines need to be generated per international guidelines. Safety assessment should demonstrate lack of plant toxicity, allergenicity, and antibiotic resistance issues. Stability testing over the product shelf life is critical to establish consistent quality and efficacy.
Several plant-produced vaccine candidates including one for Newcastle disease virus in chickens are currently in clinical trials. Successful completion of these studies will provide human safety data and pave the way for the first regulatory approvals and commercial launches of plant-made vaccines. Their impacts on reducing disease burdens globally will depend on demonstrating comparable protective responses to existing products while retaining economic and logistic advantages.
With advancements in plant molecular farming techniques and growing acceptance by regulatory bodies, plant-based vaccines have emerged as a promising platform to address the ever-increasing demands for affordable and scalable vaccine solutions. Strategic public-private partnerships will play a key role in driving their further development and applications against both human and veterinary pathogens. With optimization of key technical aspects, these vaccines hold immense potential to transform global health, especially in developing nations.
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Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc.
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