Plants are most economical and feasible production systems for vaccines or recombinant products. Replacement of fermenters and bioreactors with contained plant growth rooms or greenhouses with appropriate biological containment reduces manufacturing cost.Production costs of a recombinant protein in transgenic plants are 10 – 50-fold lower than that by E. coli fermentation. Plant vaccines can also be delivered orally, overcoming the cost and inconvenience of purification and injections. Use of plants as source of therapeutic proteins has a major advantage that productionin large quantities is possible. Feasibility for scaling up and high expression level of recombinant genes/proteins are also high in plant systems. Also,large scale cultivation is possible, and this can be adopted in less developed or resource-poor nations which lack sophisticated facilities or infrastructure for production of life-saving drugs.
Designing a recombinant vector, introduction and integration into plant system for production of antibodies, or other proteins of therapeutic value is relatively easy. The edible vaccines are easy to handle as well. When a new microbe or its antigen is evolved posing a threat to human health, it is easy to modify the synthesis of plant-based vaccines than animal-based ones. Edible vaccines are easy to deliver through oral administration and can be directly consumed without need for any injection. Edible vaccine is a needle-less vaccination method or a substitute of painful immunization procedures that require sophistication or trained manpower. It is also inexpensive, attractive to children, can be stored nearby the place of usage, harmless, and offers systemic and mucosal immunity. Edible vaccines are safe oral-delivery vehicles wherein specific plant tissues such as grains, fruits, or leaves can be used as formulation of vaccines, without extensive purification and processing. Post-translational modifications such as glycosylation, folding and assembly are significant for a protein to be biologically active and function as a vaccine.
Plants have machinery for expression, folding, assembly, and glycosylation, necessary for preservation of immunogenic activity of vaccines. In plants, the foreign or recombinant proteins of therapeutic value are glycosylated, accurately folded and the multimeric proteins assembled properly, to have structural integrity and biological activity for functioning as a vaccine.Protein synthesis as well as post-translational modifications of proteins in plants is similar to that of animal cells, making it possible to use plants as bioreactors for animal proteins/pharmaceuticals. The plantibodies or plant vaccines produced using plant-based systems are mostly safe and devoid of any toxic components.Plants do not host animal or human pathogens such as viruses or prions, as in the mammalian cell culture systems or transgenic animals, and hence do not transmit these. Chances of contamination with the pathogens during fermentation and extraction processes,is less in plant systems, Plant-based vaccines and therapeutics also have nobiosafety and environmental issues as with other animal or microbial systems of production of vaccines, except that of transgene containment.
The plant products can be stored safely for long duration at room temperature,unlike the need for refrigeration in case of other animal-based vaccines. Edibleor plant-based vaccines can also be easily produced by a freeze-dried process,leading to formulations with high stability under a cold chain-free distribution. Proteins produced in plants such as seeds remain stable for years at ambient temperatures, without loss of activity. Plant expression system has several advantages for human as well as veterinary vaccine production, however, only few of vaccine candidates are under clinical trials. Commercial human vaccines are not available due to low level of expression,relatively weak efficacy, and comparatively shallow knowledge on the characteristics of plant-made antigen and production system.Some of the challenges or constraints in the plant-based vaccines are discussed. Immunogenic response depends on nature of the vaccine, route of administration and the delivery system. Many antigens are poor immunogens, recognized poorly by the immune system and are prone to degradation in the harsh environment of the digestive tract. Plant cells protect vaccine antigen and prevent degradation as it passes through the gut.
Immunogen such as Cholera toxin Bsubunit, which can modify the cellular environment to present the antigen,can act as an efficient transmucosal carrier molecule and delivery system for plant-derived subunit vaccines and can overcome this problem. It is difficult to measure the effective dose for a mucosally delivered vaccine as it is exposed to the complex environment of the gastrointestinal tract. Further, or alvaccines may require co-administration with specific adjuvants to reach sufficient immunogenic activity. An insufficient amount of antigen would not produce the immune response needed for protection against disease and in appropriate dosage could lead to tolerance to vaccine and ineffectiveness of vaccine.