Many therapeutic proteins or N glycoproteins synthesised in plants differ in their glycosylation patterns from those derived from the mammalian systems.This may also induce increased allergenicity or reduced immunogenicity. The glycosylation pathways in plants can be altered for humanising the plant-derived vaccines or therapeutic proteins. Environmental issues of plant vaccines include gene transfer and exposure to antigens or selectable marker proteins, while risks to human health include oraltolerance, allergenicity, inconsistent dosage, worker exposure and unintended exposure to antigens or selectable marker proteins in the food chain. These risks are controllable through appropriate regulatory measures at all stages of production and distribution of a potential plant-made vaccine . The potential and prospects of plant made pharmaceuticals is restricted by the potential of transgene spread from crops through outcross, challenges in transgene bio containment, unpredictable impact of epigenetic events on transgene expression etc.
Plant cell culture bioreactors or greenhouses and use of plant virus expression systems to produce vaccine proteins in large quantities can be thought of as safer alternatives. The infamous escape of transgene in case of Prodigene and Starlink corn are examples. ProdiGene produced a transgeniccorn that expressed a vaccine for preventing bacteria-induced diarrhoea in pigs,but in 2002, ProdiGene failed to eradicate plants that had seeded from their previous season’s transgenic corn crop which contaminated non-transgenic soybeans.In 2003,the Animal and Plant Health Inspection Service of theUS Department of Agriculture made it mandatory for engineered plants producing pharmaceuticals to be grown under permit. Inefficient transgenebio containment is a serious hurdle to commercialisation of molecular pharmingusing plants. Regulatory hurdles remain a barrier to molecular farming, further increasing the cost and time, which otherwise are major advantages of plant-made vaccines.
Purification, quality controls for vaccine approval are major cost factors in vaccine production . Containment of the recombinant material is a concern which needs to be carefully monitored, to prevent these from entering the food chain and environment. The recombinant plant-based vaccines produced in transgenic plants must undergo a tight regulatory process before commercialisation.The paradigm of plant-made vaccines has evolved from vaccines consumed by world’s poorest populations through fresh producederived from their local farm, to eating engineered fruit or vegetable sprescribed by a health care worker, to a plant product derived from batch processed,freeze-dried plant tissues prescribed by a health care worker to current aradigm that PMVs are not food materials that need to meet still-evolving regulations of national regulatory authorities for drug administration and Department of Agriculture . Plants producing pharmaceuticals are regulated by USDA and the regulatory framework is developed by the FDA and Centre for Veterinary Medicine. The antigen present in edible vaccines is considered as a chemical, that does not comply with FDA rules concerning nutritional additives, but is recognized as non-GRAS.
These vaccines, under the category of food, would be included as a genetically modified food and thus are not considered a high health risk. Due to this ambiguity, a legal void currently exists with respect to regulations for standardizing edible vaccine commercialization. It is not yet clear what part of the vaccine discharges the antigen itself, the transgenic, modified fruits or the transgenic seeds . In the presence of this legal uncertainty, every country is expected to evaluate whether the entrance of edible vaccines is permitted. In 2005, the World Health Organization delivered a report on the implementation of good agricultural practices for the development of biopharmaceuticals. This report includes detailed information about methods of quality control for medicinal plants, testing to assess identity and purity, and recommended materials for plants in biopharmaceuticals. Bio-farming or molecular farming is attractive because of its flexibility, scalability,low manufacturing cost, no toxicity or pathogenic contamination, but many projects are at various developmental stages and not many are yet available to the pharmaceutical industry.
Optimization of lab protocols for up-scaling the production of therapeutics at commercial level is important for clinical use.Plant metabolic engineering is a highly significant technology for production of high-value pharmaceutical compounds. Fusion proteins for multicomponent vaccines against multiple diseases are a potential tool to incorporate into immunization programmes. Unlike genetically engineered microbial systems such as viruses, which pose more risks to the environment and humans, and have more chances of escape, difficulty in controlling and monitoring such escapes or unintended presence, plants are immobile. Control, containment and monitoring of genetically engineered plants are easier and containment can be achieved by regulating pollen transmission.