Transgenic Plants Expressing Vaccine and Therapeutic Proteins

Biopharmaceuticals in Plants Toward the Next Century of Medicine 

2 TRANSGENIC PLANTS EXPRESSING VACCINES AGAINST DIARRHEAL DISEASES 

Cholera is a devastating infectious diarrheal disease that affects over 5 million people and causes the deaths of 200,000 annually. As with LT-B, potato plants expressing CT-B induced significant levels of neutralizing 

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Transgenic Plants Expressing Vaccine and Therapeutic Proteins... 

In 1990, the first plant-made vaccines were performed via expression of Streptococcus mutans surface protein A in transgenic tobacco, followed by oral immunization of mice with the same plant material (Fischer and Emans, 2000). This transgenic plant material was later shown to successfully induce an antibody response through a demonstration that serum from immunized mice could react with intact S. mutans. Plants were also developed that expressed Escherichia coli enterotoxin B subunit (LT-B) and that exhibited successful inducement of both mucosal and serum antibody responses (Tacket, 2005). These initial experiments led to a cornucopia of studies involving generations of plant-made vaccines and therapeutic proteins and their applications in medicine. 

This chapter illustrated the broad spectrum of uses for plant-derived vaccines and therapeutic proteins. Many of the biopharmaceuticals listed in this chapter were developed in transgenic tobacco or potato plants. While tobacco is not ideal for the expression of vaccine proteins nor is raw potato ideal for oral consumption, they are both relatively easy to work with and have been well characterized, making them useful for proof-of-concept studies. The use of plants for production systems and delivery vehicles holds great promise for future biopharmaceutical development. Proteins can be produced in plants while remaining biologically functional they can be scaled up for large production and purified inexpensively and with relative ease. The following chapters describe the many attributes of plant-made biopharmaceuticals in more detail. 

The stable transformation of plants has been used routinely as a method to express vaccine and therapeutic proteins. A number of disadvantages such as the length of time taken for transgenic plants to be generated and containment (i.e., preventing the escape of transgenes into the environment) have brought about a search for alternative methods by which to express proteins in plants. One such alternative is the utilization of plant virus expression systems. 

The most widely studied therapeutic proteins produced in plants include monoclonal antibodies for passive immunotherapy and antigens for use as oral vaccines [40]. Antibodies against dental caries, rheumatoid arthritis, cholera, E. coli diarrhea, malaria, certain cancers, Norwalk virus, HIV, rhinovirus, influenza, hepatitis B virus and herpes simplex virus have been produced in transgenic plants. However, the anti-Streptococcus mutans secretory antibody for the prevention of dental caries is the only plant-derived antibody currently in Phase II clinical trials [40]. Until recently, most antibodies were expressed in tobacco, potato, alfalfa, soybean, rice and wheat [9], It has been estimated that for every 170 tons of harvested tobacco, 100 tons represents harvested leaves. A single hectare could thus yield 50 kg of secretory IgA [3, 41]. Furthermore, it has been estimated that the cost of antibody production in plants is half that in transgenic animals and 20 times lower than in mammalian cell cul-... 

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