Scientists have used chicken eggs to produce vaccines for decades, but this vaccine production method may produce allergic responses in recipients and is both costly and inefficient. Manufacturing vaccines using plants allows scientists to grow vaccines like crops and may even offer the potential for oral vaccines.
Download this poster from Drug Discovery News to learn how scientists use plants for more efficient and allergy-free vaccine production.
SCIENTISTS HAVE LONG USED PLANTS AS BASIC RESEARCH MODELS. NOW, PLANTS ARE LEADING THE WAY FOR EFFICIENT VACCINE PRODUCTION.
BY TIFFANY GARBUTT, PHD, DESIGNED BY JERRY MENSAH
What are plant-based vaccines?
In the battle against emerging infectious diseases, quickly developing effective and safe vaccines is paramount. Plants may seem like unlikely candidates for vaccine production, but they offer several unique advantages as biopharmaceutical factories. Vaccines produced by plants carry a low risk of contamination with endotoxins or mammalian pathogens. Unlike yeast-or insect-based systems, plant expression systems can introduce post-translational modifications such as glycosylation. Finally, harnessing plants as vaccine bioreactors is a robust and inexpensive way to yield effective vaccine candidates in a manner of weeks (1).
What plants can make vaccines?
While scientists have explored several plant species such as potato, tomato, and lettuce for vaccine production, Nicotiana benthamiana is the most commonly used. A relative of the tobacco plant, N. benthamiana grows quickly, can be manipulated easily, and robustly forms the unique complex structures needed for vaccine production (1,2).
How are plant-based vaccines made?
Scientists manipulate plants to produce vaccines using transient expression.
Transient expression steps for plant-based vaccine production:
1. Gene synthesis
Scientists first synthesize the gene sequences needed to produce the structural components of a pathogen.
2. Cloning
They then clone the sequences encoding the structural components into Agrobacterium tumefaciens, a soil bacterium. A. tumefaciens uniquely evolved to infect and transfer part of its DNA into plants (3).
3. Agroinfiltration
Using a process known as agroinfiltration, scientists extract the air between plant cells and immerse the plant in a bath containing the modified bacteria. The plant then readily absorbs the solution (3).
4. Growing plants for virus-like particle production
Scientists next place the plants into a controlled greenhouse. As the plants grow, they produce the structural proteins of the virus. These proteins self-assemble to form virus-like particles (VLPs) that contain the shell of the virus but no viral genome (4). Due to their structural similarity to natural viruses, VLPs elicit strong immune responses with higher levels of neutralizing antibodies. Vaccines made with VLPs are potent and do not need added adjuvants (4).
5. Harvest
After six to eight days, scientists harvest the plants and extract the VLPs for vaccine production. In total, plant-based vaccine production takes five to six weeks, a sharp contrast to the four to six months needed for egg-based vaccine production (5).
The future of plant-based vaccines
Canadian officials approved the first plant-based vaccine, which protects against COVID-19, for human use in February 2022 (6). The research team who created that vaccine is now working toward a plant-based influenza vaccine (7). In the future, plants may even facilitate the production of edible vaccines (8).
References
1. Marsian, J. & Lomonossoff, G. P. Molecular pharming – VLPs made in plants. Curr Opin Biotechnol 37, 201-206 (2016).
2. Goodin, M., Zaitlin, D., Naidu, R.A. & Lommel, S.A. Nicotiana benthamiana: its history and future as a model for plant-pathogen interactions. Mol Plant Microbe Interact 21(8), 1015-1026 (2008).
3. Chen, Q. et al. Agroinfiltration as an effective and scalable strategy of gene delivery for production of pharmaceutical proteins. Adv Tech Biol Med 1(1) (2013).
4. Moon, K. et al. Construction of SARS-CoV-2 virus-like particles in plant. Sci Rep 12 (1), 1005 (2022).
5. LeBlanc, Z., Waterhouse, P. & Bally, J. Plant-based vaccines: the way ahead? Viruses 13(1) (2021).
6. Canada authorizes first plant-based COVID-19 vaccine. The Associated Press https://apnews.com/article/coronavirus-pandemic-science-business-health-canada-c2d5bcd7a69b14d5d037aca4b76430b4 (2002).
7. Ward B. J. et al. Phase III: randomized observer-blind trial to evaluate lot-to-lot consistency of a new plant-derived quadrivalent virus like particle influenza vaccine in adults 18-49 years of age. Vaccine 39(10), 1528-1533 (2021).
8. Kurup, V. M. & Thomas, J. Edible vaccines: promises and challenges. Mol Biotechnol 62(2), 79-90 (2020).