Sarah Bennett
Scientists have been exploring the use of plants in the development of the polio vaccine. This method involves hijacking plants to create virus-like particles (VLPs) that mimic the structure of the poliovirus without being infectious. The plants read the genetic instructions and start producing these VLPs, which have been shown to prevent polio in animal experiments. This approach offers a safer alternative to traditional vaccines that use live viruses, reducing the risk of the virus escaping or regaining its dangerous traits. While there are challenges to be addressed, such as large-scale production and potential plant-related risks, the use of plants in polio vaccine development shows promise for creating effective and affordable vaccines to help eradicate polio and respond to other global health threats.
| Characteristics | Values |
|---|---|
| Plants used to make polio vaccines | Tobacco plant relative, Papilloma, Hepatitis B, and others |
| Method | Virus-like particles (VLPs) are grown in plants |
| VLP characteristics | Non-pathogenic, non-infectious, empty protein shells that 'mimic' the poliovirus |
| VLP advantages | Safer, no risk of virus escape, can provoke an immune response |
| VLP disadvantages | Low yields, high-frequency dosing, unstable |
| VLP production | Genes carrying information to produce VLPs are infiltrated into plant tissues, which then reproduce large quantities |
| VLP structure | Identical to poliovirus, confirmed by cryo-electron microscopy |
| VLP effectiveness | Protects mice from infection as effectively as existing vaccines |
| VLP applications | Can be used for priming or booster oral immunization |
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What You'll Learn
The process of 'hijacking' plants to make the polio vaccine
In 2017, scientists at the John Innes Centre in Norfolk announced a breakthrough with the potential to transform vaccine manufacture: they had hijacked plants to make a polio vaccine. The process is cheap, easy, and quick, and the scientists believe it could help the world react to unexpected threats such as the Zika virus or Ebola.
The vaccine is an "authentic mimic" of poliovirus called a virus-like particle (VLP). It looks almost identical to poliovirus but, like the difference between a mannequin and a person, it is empty on the inside. It has all the features needed to train the immune system but none of the weapons to cause an infection.
To create the vaccine, the scientists hijacked a relative of the tobacco plant's metabolism to turn its leaves into polio-vaccine "factories". First, the genetic material was implanted into bacteria, which then infected the plants. As the infection unfolded, the plants started producing the virus-like particles. To extract the particles, the infected leaves were mixed with water and blended, and the polio vaccine was then extracted.
This final part of the process is extremely simple, but the entire process is highly innovative and creative. The only thing that’s left is to scale it up, according to Professor Lomonossoff from the John Innes Centre. The beauty of it is that given the nature of the process, you don’t need more complex lab equipment to scale it up — just more greenhouses.
There are still some issues to resolve, including making the vaccine on a large scale and determining whether there is any risk from using plants to make the vaccine. For example, does the tobacco-relative mean there is nicotine in the vaccine? However, if this technology lives up to its potential, we may be within reaching distance of truly exterminating polio.
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The potential risks of using plants to make the vaccine
While the use of plants to make vaccines, such as the polio vaccine, has been hailed as a breakthrough with the potential to transform vaccine manufacture, there are some potential risks and challenges that need to be addressed.
One of the main concerns is the risk of contamination. Open-field cultivation of genetically modified plants increases the possibility of contamination of non-transgenic crops intended for human or animal consumption. Recombinant genes can spread to field crops via pollen, resulting in unintended genetic modifications in non-target plants. This could lead to the consumption of genetically modified plants by wild animals or accidental harvesting by humans. Additionally, contact with insects and the release of contaminated water into the environment are potential mechanisms for DNA or antigen escape. The probability and severity of these risks depend on the specific plant species and antigen involved, requiring a case-by-case assessment for each plant-based vaccine.
Another issue is the limited number of plant-based vaccine manufacturers and licensed human vaccines currently produced in plants. Dr. Tarit Mukhopadhyay, a lecturer in vaccine development, noted that there are very few plant-based vaccine manufacturers, and most human vaccines are not produced in plants. This highlights the need for further research and development in this area.
The use of transgenic technologies in plant-based vaccines also raises biosafety concerns, including the risk of contaminating the food chain and the development of oral tolerance to edible vaccines. Proper regulatory measures, monitoring, and risk management are essential to mitigate these potential risks. The World Health Organization (WHO) has recommended applying guidelines on Good Agricultural and Collection Practices (GACP) to plants producing biopharmaceuticals, with the United States Department of Agriculture (USDA) playing a key role in approving veterinary biologics and considering various factors, such as the nature of the plant and risk-management strategies.
Furthermore, there are challenges in large-scale production and maintaining quality standards. While plants offer a rapid and responsive platform for vaccine development, scaling up production requires sufficient space and resources for growing more plants. Additionally, facilitating the manufacturing and processing of plant-based pharmaceuticals without compromising quality is crucial for human and animal vaccine production.
Lastly, the specific plant used in the polio vaccine, a relative of the tobacco plant, raises the question of nicotine presence in the vaccine. This concern needs to be addressed through rigorous testing and evaluation to ensure the vaccine's safety and efficacy.
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The advantages of using plants to make the vaccine
Plants have been used to create vaccines, including for polio, in a process that scientists say is cheap, easy, and quick. Here are some advantages of using plants to make vaccines:
Speed
The process of using plants as bio-factories to produce vaccines is quick. It takes about six to eight weeks to go from genetic sequence to clinical-grade material. In comparison, vaccines grown in chicken eggs can take months to develop.
Safety
Plants are not hosts for human and animal pathogens, making them a safe option for vaccine production. Recombinant subunit vaccines, which are often expressed in plants, are also safer than traditional vaccines because they contain no live pathogens.
Cost-effectiveness
Using plants for vaccine production is cost-effective. Plants are inexpensive to grow on a large scale in greenhouses, bioreactors, or open fields.
Ease of production
Plants are easy to use for vaccine production. They require only sunlight, soil, water, and carbon dioxide to grow. Additionally, agroinfiltration, a technique used in vaccine production, allows for the production of large amounts of vaccine proteins within a few days to a couple of weeks.
Scalability
Plant-based vaccine production is easily scalable. Plants can be grown in various environments, and specific plant viruses allow for the dense expression of fused antigens, contributing to an effective immune response.
While there are some challenges to using plants for vaccine production, such as low yields and the need for further research and development, the advantages outlined above highlight the potential of plant-based vaccines as a safe, effective, and efficient solution for disease control and prevention.
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The structure of plant-produced poliovirus vaccines
Polioviruses are highly infectious viruses that are spread mainly through the fecal-oral route. Infection of the central nervous system frequently results in irreversible paralysis, a disease called poliomyelitis. Children under five years of age are mainly affected if they have not acquired immunity through natural infection or vaccination.
There are two types of polio vaccines: the inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends that all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of theworld, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.
During the last fifteen years, plant-based poliovirus vaccines have been explored by several groups as a safe and low-cost alternative, and promising results in protection against challenges with viruses and induction of neutralizing antibodies have been obtained. The process is cheap, easy, and quick, and it has the potential to transform vaccine manufacture, say scientists. The vaccine is an "authentic mimic" of poliovirus called a virus-like particle (VLP). Outwardly, it looks almost identical to poliovirus but is empty on the inside. It has all the features needed to train the immune system but none of the weapons to cause an infection.
The generation of poliovirus VLPs containing the capsid proteins was first reported by Marsian et al. in 2017. Stable VLPs were generated (yield up to 60 µg/g) that retained the native, immunogenic D antigenic conformation. Transgenic mice expressing the poliovirus receptor were intraperitoneally immunized with purified plant-produced VLPs carrying poliovirus antigens. Importantly, the immunized mice showed protection after challenge with a wild poliovirus 3 strain, and structural analysis of the VLPs demonstrated a morphology resembling native polioviruses. In a later study, Daniell et al. (2019) developed transplastomic lettuce lines suitable for oral immunization. VP1 was assembled as a VLP of approximately 22.3 nm in size.
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The effectiveness of plant-produced poliovirus vaccines
Polioviruses are highly infectious and are transmitted mainly through the fecal-oral route. Infection of the central nervous system can result in irreversible paralysis, known as poliomyelitis, which primarily affects children under five. The injectable inactivated polio vaccine (IPV) and the live-attenuated oral polio vaccine (OPV) are the two main types of polio vaccines currently available. However, both vaccines have limitations, such as reduced protection at the intestinal mucosa for IPV and the possibility of reverting to pathogenic viruses for OPV.
In recent years, plant-based poliovirus vaccines have emerged as a potential solution to these challenges. By "hijacking" plants, researchers have been able to create virus-like particles (VLPs) that mimic the structure of poliovirus but lack the ability to cause infection. This approach offers several advantages, including the ability to quickly identify new virus strains and produce candidate vaccines within a short timeframe. Additionally, plants have the benefit of rapid growth and simple requirements, such as sunlight, soil, water, and carbon dioxide.
The process of creating plant-produced poliovirus vaccines involves delivering a transgene into the plastid or nuclear genome of the plant or using RNA-based viral expression systems. Edible plants like carrots or lettuce are ideal for oral vaccines as they lack toxic compounds and require minimal processing. Plant cells can also enhance the effectiveness of viral antigens through natural encapsulation and adjuvant-intrinsic effects. Chloroplast expression, in particular, offers high protein expression levels due to the high number of DNA copies per chloroplast and organelles per leaf cell.
However, there are still challenges to be addressed with plant-produced poliovirus vaccines. One issue is the low expression levels and yields of poliovirus proteins, which may be improved by co-expressing human chaperones like HSP90. Another challenge is the limited number of plant-based vaccine manufacturers and licensed human vaccines produced in plants. Nevertheless, the development of plant-produced poliovirus vaccines holds promise as a safe, low-cost, and responsive alternative to traditional vaccines, with the potential to transform vaccine manufacture and address emerging global health threats.
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Frequently asked questions
Yes, scientists have found a way to use plants to make polio vaccines.
Scientists use a method that involves growing virus-like particles (VLPs) in plants. Genes that carry information to produce VLPs are infiltrated into the plant tissues. The host plant then reproduces large quantities of them using its own protein expression mechanisms.
VLPs are non-pathogenic and non-infectious mimics of the poliovirus. They look like viruses but do not contain the genetic material that allows viruses to replicate.
A relative of the tobacco plant has been used to make the polio vaccine.
Using plants to make the polio vaccine is cheap, easy, and quick. It is also safer than using live viruses to make the vaccine, as there is a risk of the virus accidentally escaping and re-introducing polio.
