Production of Green Vaccines

INTRODUCTION: In this era where the world population is increasing exponentially, providing the best health care to all is questionable, not only due to accessibility but also due to affordability. Vaccination is considered to be the most efficient and cost-effective health intervention. However, the high cost of vaccination makes it unaffordable for most people living in developing countries because of their unnecessarily complex production and delivery methods, including the significant cost of fermentation systems to purification through the use of complex technologies and additional expenses associated with adjuvant, cold storage, transportation and sterile delivery. This void can be addressed through the use of plant cells as bioreactors for the production and oral delivery of vaccine antigens. Since plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. This novel approach uses freeze-dried plant cells for bio-encapsulation of vaccine antigens that protect them in the stomach from acids and enzymes but are released to the immune system in the gut, when plant cell walls are digested by bacteria that colonize the gut.

Production of Green Vaccines

Green vaccines production involves the integration of transgene into the plant cells. Steps of production involve; selection of target sequence of selected antigen, integration of target sequence into vector and expression of transgene in plants. The target sequence of the selected antigen is integrated with the vector before being transferred into the expression system. The integration of transgene can be done by following methods; biolistic method which is a direct method, indirect methods like Agrobacterium mediated gene transfer and genetically engineered plant virus. The efficiency of Gene delivery can be increase by DNA uptake by chemical stimulation, sonication and sonication with vacuum infiltration assisted Agrobacterium mediated gene transfer. The transgene can then be expressed in the plants either through a stable transformation system or through transient transformation system. Stable transformation system can be achieved through nuclear or plastid integration. Biolistic and genetically modified Agrobacterium strain can lead to the formation of stable transfection. However, as Agrobacterium tumefaciens is not infecting many plant species naturally, it limits the application of Agrobacterium strain for stable transformation of the desired gene. While, transient transformation system involves the production of desired protein or antigen soon after the heterologous gene resides transiently in the host cells. The transgene is not incorporated into the genome of the plant cells. In this plant expression system, the regeneration of whole plant is not required and the frequency of its occurrence is higher. These characteristics overcome the pitfalls related to the stable integration. Most common methods for transient expression of a desired protein are the Agrobacterium-mediated transformation and particle bombardment.

Advantages of Plant-Based Vaccines

• Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery.

• The use of plant cells as bioreactors for the production and oral delivery of vaccine antigens can be done to reduce the void and also this method of vaccine production is cheap as compared to the commercial vaccine production methods.

• The Plant based vaccines are produced naturally hence its consumption is safe to both environment and the patient. These vaccines will be highly beneficial for the patients with diseases like diabetes, tuberculosis who need to take regular medicines.

Challenges of Plant-Based Vaccines

Many plant-based vaccines that have been produced, but they are still in phase 1 clinical trial, some vaccines have proceeded or completed phases II and III trials after which they will be ready for market. Many therapeutics such as insulin in transgenic safflower (SemBioSys) and Ebola Vaccine in transgenic tobacco (Mapp Biopharmaceutical) were produced in various transgenic plants, but still there is no plant made vaccine that has been approved for human consumption commercially. Usually there are three major challenges; the selection of antigen and plant expression host, consistency of dosage, and manufacturing of vaccines according to Good Manufacturing Practice (GMP) procedures.

Selection of Antigen and Plant Expression Host

This stage is very important in developing a vaccine that is able to fulfil all the requirements needed because not all antigens are compatible with the selected host plants. The proper and careful selections will help to determine the safety of the vaccine produced, and it can be used to produce thermal-stable vaccine. Identification of antigen candidate of poorly characterized pathogen with promising characteristics can be done by applying genomics or proteomics approaches.

Consistency of Dosage

It is another challenge researchers have to face as dosage produced may vary within the plants of the same species, from fruit to fruit and from generation to generation due to the size and ripeness of the fruits or plants. Since the transgenic plants show intrinsic variability in the antigen expression due to the position and pleiotropic effects caused by non-specific integration of the transgene into the host plant genome. Besides that, gene silencing might be induced due to the accumulation of mRNA in the transgenic plant cells as the growth of the plants is stopped and the fruit formation is reduced while the antigen content is increased. In such case, consumption of plant-based vaccines may induce allergic reaction and few side effects such as toxicity on central nervous system, cytokine-induced sickness, and autoimmune diseases.

Conclusion: Efficient and cost-effective vaccination is the need of the hour since high cost of vaccination makes it unaffordable for most people living in developing countries because of their unnecessarily complex production and delivery methods. Green vaccines can be an answer to many incurable diseases hence further research work need to done.