Biopharmaceuticals vaccine, transgenic plants

In order to overcome environmental concerns in particular, some companies are investigating the use of engineered plant cell lines as opposed to intact transgenic plants in the context of biopharmaceutical production. One company (DowAgroSciences) gained approval in 2006 for a veterinary subunit vaccine against Newcastle disease in poultry produced by such means. 

Transgenic plants present enormous potential to become one of the most cost-effective and safe systems for large-scale production of proteins for industrial, pharmaceutical, veterinary, and agricultural uses. Over the past decade, much progress has been made with respect to the development of vaccines, antibodies, and other therapeutic proteins. Biopharmaceuticals in Plants Toward the Next Century of Medicine provides a comprehensive survey of ail major aspects of the development and production of plant-made biopharmaceuticals. 

Transgenic plants might also be used for production of recombinant proteins. While many of these systems are still early in the development stage, plants offer very robust and high-capacity system for biopharmaceutical production. Since plants cannot always properly modify proteins as mammalian cells, their utility may be limited. However, early studies suggest that plants may serve as useful hosts for production of vaccines and antibodies. For example, HepB surface antigen has been successfully expressed in potatoes [11], and clinical trials are underway with secretory antibodies (SIgAs), such as CaroRx , developed in plants [12]. 

Table 8.1 lists examples of vaccines produced in transgenic plants. Table 8.2 shows several possibilities for antibody production in transgenic plants and Table 8.3 demonstrates the range of biopharmaceuticals under development from transgenic plants. 

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 potential of flow of plant-made biopharmaceuticals into the human food chain remains. For example, plant-derived pharmaceuticals could cross-contaminate foodstuffs by spontaneous growth of transgenic crops in areas outside the intended field, or by pollen flow between some plants such as corn. It has been suggested that plant-derived biopharmaceuticals should be generated in nonfood crops, such as tobacco. However, food crops produce the greatest opportuitities for efficient production since they are among the most well-studied of crops. This continues to make them more feasible for edible vaccine production. 

Tackaberry ES, Dudani AK, Prior F, et al. Development of biopharmaceuticals in plant expression systems cloning, expression and immunological reactivity of human cytomegalovirus glycoprotein B (UL55) in seeds of transgenic tobacco. Vaccine, 1999 17(23/24) 3020-3029. 

Yeast is the third expression system used to produce biopharmaceuticals. As mammalian systems, they possess the ability to cany out post-translational modifications of proteins, although the glycosylation pattern usually varies somewhat from the patterns observed on the native protein or on the protein expressed in mammalian cells. Two recombinant proteins expressed in Saccharomyces cerevisiae are now approved for general medical use hepatitis B surface antigen vaccine and the anticoagulant Hirudin . Alternative promising production systems, in particular transgenic animal and plant systems, are still in development but these systems have to prove that they are technically and economically attractive. 

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