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A Seed-Derived Oral Subunit Vaccine for Human Cytomegalovirus

  • Chapter
Molecular Farming of Plants and Animals for Human and Veterinary Medicine

Abstract

Transgenic plants offer many potential advantages as production systems for making human biopharmaceuticals. Subunit vaccines are especially promising candidates for this technology since it may also be possible to administer the recombinant protein vaccinogen orally, in edible plant products. In order to study this promising approach we have established a model system to express the major glycoprotein, gB, of human cytomegalovirus (HCMV) in the seeds of tòbacco plants. A novel expression vector was developed incorporating regulatory sequences of glutelin, the major rice seed storage protein, to direct synthesis of recombinant glycoprotein B to seeds. Following transformation, selected calli and subsequently mature plants were regenerated. Screening of genomic DNA by PCR amplification and Southern blotting showed that 71% harboured the gB coding sequence. Specific immunoassays were established using neutralizing and non-neutralizing monoclonal antibodies specific for gB. These revealed that protein extracts from seeds of positive plants produced antigenic gB at levels ranging from 70–146 ng/mg extracted protein. In addition, similarity with native gB produced in HCMV-infected cells was demonstrated by inhibition of immunofluorescence on HCMV-infected human fibroblasts. Although several mammalian proteins have been expressed in tobacco, localization of the proteins within transgenic tissues has not been extensively examined. In order to identify the site(s) of recombinant gB deposition in mature tobacco seeds, we used immunogold labelling and electron microscopy. We observed specific labelling for gB in the endosperm of transgenic seeds, with gB localized almost exclusively in protein storage vesicles. This was found equally in seeds that were freshly harvested and in seeds that had been stored at room temperature for several months. Collectively, our results demonstrate that this large and complex viral glycoprotein can be expressed in plants in a highly tissue-specific manner. They also show that biologically significant structural features, including viral neutralizing epitopes, are retained in this heterologous system, and that the gB is sorted within seeds in a manner similar to plant storage proteins. These data provide further evidence to support the suitability of plants for producing recombinant proteins of potential clinical relevance.

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Authors and Affiliations

  1. Bureau of Biologics and Radiopharmaceuticals, Therapeutic Products Programme, Health Canada, Ottawa, K1A 0L2, Canada

    E. S. Tackaberry, A. K. Dudani & P. R. Ganz

  2. Department of Biochemistry, Microbiology and Immunology, K1N 6N5, Canada

    E. S. Tackaberry, K. E. Wright & P. R. Ganz

  3. Department of Cellular and Molecular Medicine, University of Ottawa, K1N 6N5, Canada

    A. K. Dudani

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  1. E. S. Tackaberry
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  2. K. E. Wright
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  3. A. K. Dudani
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  4. I. Altosaar
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Editors and Affiliations

  1. Department of Plant Agriculture, University of Guelph, Geulph, Ontario, Canada

    L. Erickson

  2. Syngenta Biotechnology Inc., Research Triangle Park, North Carolina, USA

    W.-J. Yu

  3. Research Branch, Agriculture and Agri-Food Canada, London, Ontario, Canada

    J. Brandle  & R. Rymerson  & 

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Tackaberry, E.S., Wright, K.E., Dudani, A.K., Altosaar, I., Ganz, P.R. (2002). A Seed-Derived Oral Subunit Vaccine for Human Cytomegalovirus. In: Erickson, L., Yu, WJ., Brandle, J., Rymerson, R. (eds) Molecular Farming of Plants and Animals for Human and Veterinary Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-2317-6_6

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