April Journal-2009.p65 - Association of Biotechnology and Pharmacy

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Current Trends in Biotechnology and Pharmacy Vol. 3 (2) 113-127, April 2009. ISSN 0973-8916 Transgenic plants not only provide the means to express antibodies but also enable the glycosylation and entry into secretory pathway which allow assembly of complete antibodies and Fab fragments. Variable fragments (Fv) can be produced in cytosol, directed to different compartments and fused with proteins such as protein A and phosphatase to improve the detection and purification of single chain Fv (scFv). In plants, antibody production (1-5% of total plant protein) has been achieved by crosspollination of individually transformed plants expressing light or heavy chains (29). Other approaches involve double transformation or transformation by constructs having genes for both light and heavy chains on the same vector. Despite the fact that production of antibodies in plants takes longer, the low cost of production and capability of increasing production simply by increased propagation make plant antibodies an attractive proposition. Aiming at therapeutic treatment (14) , have succeeded in producing multimeric secretory IgA (SIgA) molecules in plants which represent the predominant form of immunoglobulin in mucosal secretions. SIgA not only contains heavy and light chains but it is also dimerized by a J chain, and protected from proteolysis by a fourth polypeptide, the SC. Production of such antibodies in mammalian cells is very complex because of the requirement of B cell as well as gut epithelial cells for the formation of the SIgA. Thus, four transgenic tobacco plants were produced by genetic engineering which produced a murine monoclonal antibody light k chain, the hybrid IgA- G antibody heavy chain, murine J chain and rabbit secretory component. A series of sexual crosses was carried out to allow expression of all the four proteins simultaneously. The progeny produced a functional secretory immunoglobulin very efficiently. This demonstrated the potential of plants in assembly of antibodies, and the flexibility of system. Recently, a humanized monoclonal 122 antibody against glycoprotein B of herpes simplex virus 2 (HSV-2) has been expressed in soybean. This antibody was found to possess the same efficacy for prevention of vaginal HSV-2 infection in mice and similar stability in human semen as the antibody expressed in human cell culture (52) and also plant cell cultures (23). Topical application of antibodies has already been shown to control infection by way of passive immunization. A hybrid monoclonal antibody (IgA/ G), having constant regions of IgG and IgA fused, has been used successfully against human dental caries caused by the bacterium Streptococcus mutans (33). Ma et al. (1998) compared the secretory antibody produced in transgenic tobacco (SIgA/G) and the original mouse IgG. Though both had similar binding affinity to surface adhesion protein of S.mutans, SIgA/G survived for three days in the oral cavity, whereas IgG could survive for just one day. The plant antibody provided protection against the colonization of the S. mutans for at least four months. These results show that this strategy could be useful for many other mucosal infections in humans and animals. Medical molecular farming has been done for the production of antibodies, biopharmaceuticals and edible vaccines in plants for immunotherapy (16, 31 and 32). Co-expression of soybean glycinias A1 aB 1b and A3B4 enhances their accumulation levels in transgenic rice seeds (62). Scope for future study Vaccines have been one of the most farreaching and important public health initiatives of the 20 th century. Advancing technology, such as oral DNA vaccines, intranasal delivery and edible plant derived vaccines, may lead to a future of safer and more effective immunization. Edible vaccines, in particular, might overcome some of the difficulties of production, distribution and delivery associated with traditional vaccines. Significant challenges are still to be overcome before vaccine crops can become a reality. Plant Derived Edible Vaccines
Current Trends in Biotechnology and Pharmacy Vol. 3 (2) 113-127, April 2009. ISSN 0973-8916 However, while access to essential healthcare remains limited in much of the world and the scientific community is struggling with complex diseases such as HIV and malaria, plant derived vaccines represent an appetising prospect. The potential advantages of plant based vaccines are edible means of administration, reduced need for medical personnel and sterile injection conditions, economical to mass produce and transport, reduced dependence on foreign supply, storage near the site of use, heat stable, eliminating the need for refrigeration, antigen protection through bioencapsulation, subunit vaccine (not attenuated pathogens) means improved safety, seroconversion in the presence of maternal antibodies, generation of systemic and mucosal immunity, enhanced compliance (especially in children), delivery of multiple antigens, and integration with other vaccine approaches. Acknowledgement- The author is highly thankful to Dr. Diane E. Webster, Department of Medicine, Monash University Medical School, Alfred Hospital, Prahran, VIC, for copied figure from his research idea. References 1. Arakawa, T., Chong, D.K.X., and Langridge, W.H.R. (1997). Expression of Choleratoxin B subunit oligomers in transgenic potato plants, Transgenic Res, 6: 403-413 2. Arakawa, T., Chong, D.K.X. and Langridge, W.H.R. (1998). Transgenic plants for the production of edible vaccine and antibodies for immunotherapy, Nature Biotechnol, 16: 292-297 3. Arakawa, T., Yu, J. and Chong, D.K.X. (1998). A plant based cholera toxin B subunit insulin fusion protein protects against the development of autoimmune diabetes, Nat. Biotechnol., 16: 934-938 123 4. Arntzen, C.J. (1998). Pharmaceutical foodstuffs-oral immunization with transgenic plants, Nature Medicine (supplement), 4: 502-03 5. Artsaenko, O., Peisker, M., Zurniedan, U., Fielder, U., Weiler, E.W., Muntz, K., Conrad, U. (1995). Expression of a single chain FV antibody against abscisic acid creats a wilty phenotypes in transgenic tobacco, Plant J., 8: 745-750 6. Baum, T.J., Hiatt, A., Parrott, W.A., Pratt, L.H., Hussey, R. S. (1996). Expression in tobacco of a monoclonal antibody specific to secretion of the root knot nematode, Mol. Plant Microbe Interact., 9: 382-387 7. Benvenuto, E., Ordas, R.J., Tavazza, R., Ancora, G., Biocca, S., Cattaneo, A. and Galeffi, P. (1991). Phytoantibodies: A general vector for the expression of immunoglobular domains in transgenic plants, Plant Mol. Biol., 17: 865-874 8. Carter, J.E.III and Langridge, W.H.R. (2004). Plant based vaccine for protection against infectious and autoimmune diseases, Crit. Rev. Plant Sci., 21: 93-109 9. Carrillo, C., Wigdorovitz, A., Oliveros, J.C., Zamorano, P.I., Sadir, A.M., Gomez, N., Salinas, J., Escribano, J.M. and Borca, M.V. (1998). Expression of immunogenic S1 Glycoprotein of infectious Bronchitis virus in transgenic potatoes, J.Virol., 72: 1688-1690 10. Carrillo, C.A., Wigdorovitz, K., Trono, M.J., Dus Santos, S., Castanon, A.M., Sadir, R., Ordas, J.M., Escribano, J.M., Borca, M.V. (2001). Induction of a virus-specific antibody response to foot and mouth disease virus using the strain VP1 expressed in transgenic potato plants, Viral Immunol., 14:49-57 Das et al
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