Vaccine protein production

PI. polymorpha [80] is generally referred to as safe and was widely used for pharma-protein production (cytokines, vaccines, coagulation factors) [80]. The genome sequence is known and DNA chip technologies have been established. Hansenula was developed to an expression platform which was implemented for the production of recombinant vaccines. 

Most of the recombinant subunit vaccines tested in the first half of this decade employed gp 120 or gp 160 expressed in yeast, insect or mammalian (mainly CHO) cell lines. Eukaryotic systems facilitate glycosylation of the protein products. Like all subunit vaccines, these stimulate a humoral-based immune response but fail to elicit a strong T-cell response. The failure to elicit a cell-based... 

Developmental promoters that have been commonly used for vaccine production include patatin and E8 promoters derived from potato and tomato, respectively. Patatin is one of the major soluble proteins in potato tubers and is encoded by a multigene family. The patatin promoter is tuber-specific the protein is expressed in tubers but not in leaves (Grierson et al., 1994). Patatin has been shown to express vaccine protein in potato tubers at levels greater than the CaMV 35S promoter (Rocha-Sosa et al., 1989). 

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. 

Since plastids have a limited set of protein degradation pathways, foreign proteins that exhibit harmful effects to the plant in the cytoplasm may be more stable when they accumulate within the chloroplast (Heifetz, 2000). For example, the vaccine protein cholera toxin B subunit was shown to be toxic even when it accumulated to very low levels within the plant cytoplasm, but was nontoxic when it accumulated to large quantities within the chloroplast. Plastids also possess the ability to form disulfide bonds, a requirement for many correctly folded mammalian proteins (Daniell et al., 2005a). These properties have made them attractive for the production of biopharmaceuticals in plants. 

Azhakanandam, K., Weissinger, S.M., Nicholson, J.S., Qu, R and Weissinger, A.K. (2007). Amplicon-plus targeting technology (APTT) for rapid production of a highly unstable vaccine protein in tobacco plants. Plant Mol. Biol. 63 393-404. 

Pogrebnyak, N., Golovkin, M., Andrianov, V., Spitsin, S., Smirnov, Y, Egolf, R., and Koprowski, H. (2005). Severe acute respiratory syndrome (SARS) S protein production in plants development of recombinant vaccine. Proc. Natl. Acad. Sci. U.S.A. 102(25) 9062-9067. 

There are a number of examples of the development of plants for pharmaceutical protein production including antibodies, vaccines, and other bioactive proteins (Daniell et al., 2001 Daniell, 2006 Ma et al., 2005a, b, c Twyman et al., 2003) as well as consideration of the issues surrounding regulatory issues of the use of transgenic plants for pharmaceutical protein applications (Ma et al., 2005b Sparrow et al., 2007 Spok, 2007). 

The definition of a process based on biotechnology is sufficiently broad to capture a wide arrange of medicinal products, such as recombinant proteins and gene-based therapeutics, and prophylactics, such as gene transfer medicinal products and DNA vaccines. Medicinal products manufactured by biotechnological processes as defined in the Annex to Regulation (EC) 726/2004 must be authorized centrally pursuant to article 3 of the Regulation. 

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