It was for the first time proved by National Institute of Allergy and Infectious Diseases that significant immunogenicity can be induced safely by an edible vaccine. After two years, antigens of Norwalk virus were expressed in potato .The nor walk virus antigens were expressed in transgenic tomatoes as well. Similarly,rabies glycoprotein and hepatitis B surface antigen were expressed in spinach and lettuce respectively. Plant as a bioreactor is cheaper, easy-to-handle, requires no sophisticated or cold storage facilities, easy to scale up, cost-effective or less-expensive production, involves effective, convenient and easy route of administration. Bacterial, viral, parasitic and immune-contraceptive vaccines can be produced in plants as edible vaccine .The first chimeric gene expressed in plants was human growth hormone expressed in sunflower and tobacco plants, transformed through Agrobacterium-mediated transformation.
First generation plant-based vaccines were produced against influenza virus, human papilloma virus and norovirus by modifying PVX or TMV. In second generation plant-based vaccines, deconstructed viral vectors devoid of different viral elements needed for its replication and infectivity were used. Recombinant viral vectors with heterologous coat protein, with cell surface presentation of foreign antigen in the viral coat protein and sub-genomic promoters etc were more stable, environmentally safe and provided high yield.Potato and tobacco were used as model organisms initially in development of plant-based vaccines. Potato was used as model plant in edible vaccine production since it was easy and efficient to transform, tuber-specific promoters could be used to express transgene/antigen gene, outcrossing risk was low, clonal propagation to produce stable transgenics was possible, tubers could be eaten, were used in food industry and tubers could be stored for long periods without refrigeration.
Tobacco and alfalfa have leaves which are major source of biomass; banana, tomato, apple, guava and strawberry were the fruit crops; peanut,corn, soybean and chickpea were seed-based crops; cabbage, lettuce, potato,carrot and spinach are the vegetable plants which were used for the production of vaccine antigens.Plant vaccines have been developed for many human diseases such as hepatitisB, Human Immunodeficiency virus , rabies etc. More than 25 vaccines licensed for use in humans with many more in the development pipeline . In March 2018, Medicago Inc. conducted phase III clinical trials to develop flu vaccine in tobacco and is expected to be launched in the market by 2020-2021. In June 2018, researchers from the University of Nottingham, Malaysia, launched a project to develop plant-based vaccine against dengue fever, caused by Aedesmosquitoes. Researchers from Arizona State University’s Biodesign Institute,developed a norovirus vaccine from tobacco plant in August 2018. Other than tobacco, many edible crop plants are also used such as the dengue virusvaccine produced in lettuce through chloroplast transformation in 2016.
MedicagoInc., iBio Inc., Icon Genetics-GmbH, Creative Biolabs etc. are involved in plant-based vaccine development. The Queensland University of Technology,Australia plans to use the genome sequence information of Nicotiana benthamiana to use the plant as biofactory to produce antibodies, vaccines and therapeutics,to develop protein-based diagnostic products in bulk quantities at a lowcost against COVID-19 or similar viruses or pathogens.Although plant-based human vaccines are not approved yet, vaccines against influenza, norovirus, hepatitis B virus, rabies virus etc. have been successfully produced in various transgenic plants and tested for their safety and efficacy under clinical trials . Vaccines against several animal diseases have been developed in plants, tested in animal models and in target animal species with the disease. Vaccines against anthrax, Bovine Herpes virus 1, enterotoxigenic E. coli etc. were produced in tobacco. The Foot and Mouth Disease virus VP1 epitope were expressed in alfalfa and Arabidopsis leaves and potato tubers, while the FMD virus polyproteinP1-2A/protease 3C was expressed in tomato. Epitopes of mink enteritis virus, murine hepatitis virus and rabbit haemorrhagic disease virus were produced through cowpea mosaic virus display in cowpea, Tobacco Mosaic Virusepitope display in tobacco and Plum pox virus epitope display in tobacco respectively.The infectious bronchitis virus S1 glycoprotein was expressed in potato tuber while transmissible gastroenteritis coronavirus glycoprotein N terminal domain was expressed in maize grains.
Bovine trypsin derived from maize has been commercialized since 2002.Neutralizing antibody responses were elicited against homologous and heterologous Newcastle Disease virus by inoculating plant-produced fusion protein antigen ,into Specific Pathogen Free chickens. Newcastle disease vaccine derived from tobacco cells was first approved for poultry use by United States Department of Agriculture .In addition to expression of antigen for vaccine production ,pharmaceuticals such as antibodies, enzymes, therapeutically important proteins or peptides and growth hormones are produced in plants . The vaccines used for immunisation against contagious disease are mostly costly and not easily accessible. On the contrary, the plant bioreactors are cost-effective and cheaper.