Recent Advances in Virus Expression Vector Strategies for Vaccine Production in Plants

Plants offer tremendous advantages as cost-effective and safe platforms for the large-scale production of vaccines and other therapeutic proteins. Plant-derived vaccines represent a means by which to enhance vaccine coverage for children in developing countries, and can be administered orally to elicit a mucosal immune response. Plantderived vaccines possess the dual advantage of preventing the antigen from degradation as it passes through the gastrointestinal tract, while at the same time being capable of delivering an antigen to the mucosal immune system. Plant virus vectors have been designed to express vaccine epitopes as well as full therapeutic proteins in plant tissue. This review describes recent advances with respect to plant virus expression vectors used as production platforms for biopharmaceutical proteins. *Corresponding author: Kathleen Laura Hefferon, Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada, E-mail: [email protected] Received February 03, 2012; Accepted March 08, 2012; Published March 13, 2012 Citation: Hefferon KL (2012) Recent Advances in Virus Expression Vector Strategies for Vaccine Production in Plants. Virol Mycol 1:105. doi:10.4172/21610517.1000105 Copyright: © 2012 Hefferon KL. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction The leading cause of infant mortality in developing countries persists from infectious diseases which are readily treatable in the industrialized world. One tactic used to combat this problem has been the establishment in 1992 of the Children’s Vaccine Initiative, a platform by which globally accessible oral vaccines are generated through an assembly of philanthropic groups in conjunction with the World Health Organization. New vaccines developed under this initiative would be inexpensive, efficacious, safe, easy to transport to remote areas, and temperature stable [1,2]. The use of plants as production and delivery platforms for the expression of vaccine and therapeutic proteins is one promising approach that emerged from this Initiative. Biopharmaceutical proteins produced in plants retain the same structural integrity and activity as their mammalian-derived counterparts, contrary to bacterial expression systems. Vaccines produced from plants are protected from degradation by the harsh environment of the gastrointestinal tract via the plant tissues themselves, and can thus reach the mucosal immune system more effectively [3]. Vaccines and therapeutic proteins are now expressed stably in the form of transgenic plants, in a transient fashion by techniques such as agroinfiltration, or even by infection using recombinant virus expression vectors [4-6]. Gastrointestinal diseases such as infantile diarrhea remain significant causes of morbidity and mortality in many developing countries. Plant-made vaccines have the potential to enhance vaccine coverage in children and infants, particularly in resource-poor regions where such diseases remain a problem. Oral consumption of plantbased vaccines would be well suited for combating gastrointestinal diseases, and this possibility has been examined in the form of several Phase 1 clinical trials [7]. Many antigens do not become recognized by the gut as foreign and as a result cannot serve as immunogens. The use of adjuvants, which can affect the immunogenic context in which an antigen is encountered, is one way to overcome this problem. One of the most commonly used mucosal imunogens for plant-derived vaccine delivery is the cholera toxin subunit B (CT-B). Lacking toxicity to the cell, CT-B can not only modify the cellular environment in order to present the antigen in a highly efficient manner, but can also act as an efficient transmucosal carrier molecule and delivery system for plant-derived subunit vaccines [8]. In this instance, proteins which exhibit weak immunogenicity are coupled to CT-B and are then expressed in plant tissue. Proteins presented as a fusion protein of CT-B exhibit increased antigenicity within the gut [9]. A principal driving force for plant-derived biopharmaceuticals has been its expected potential to provide relief to Third World countries. Twenty percent of the world’s infants remain unimmunized as a result of limitations on vaccine accessibility [10]. A number of infectious diseases such as dengue fever, hookworm and rabies are less renowned and treatments are poorly financed; developing vaccines in plant expression platforms could offer an opportunity to treat these ‘orphan’ diseases [10,11]. What makes plant virus expression vectors particularly attractive are the fact that the require no lengthy steps of plant transformation, yet they can express substantial levels of the gene of interest on a massive scale rapidly, often within a few days, by merely increasing the number of host plants. Moreover, vaccine proteins can be purified inexpensively from plants, or depending on the intended usage, may require only partial purification. Besides providing vaccines and therapeutic proteins to those who reside in developing countries, plant virus expression vectors offer alternatives for other reasons as well. Production platforms based upon plant viruses have been used to produce vaccines against possible biological warfare agents, global pandemics and even certain cancers. Together, these applications provide compelling motivation towards further developing plant viruses as a technology to produce biopharmaceuticals and other proteins in plants. A large number of mammalian therapeutic proteins are glycosylated, and plant proteins also undergo post-translational modifications; however, they are not identical to their mammalian counterparts. One end result of these subtle differences in glycosylation motifs between plant and mammalian derived therapeutic proteins could be an increase in allergenicity and other undesirable immune responses [12]. Today’s plant glycobiologists have been able to further ‘humanize’ therapeutic proteins such as immunoglobulins by altering a variety of plant glycosylation pathways [13,14]. For example,