Strategies for the plant‐based expression of dengue subunit vaccines

Abstract

Despite significant efforts in many countries, there is still no commercially viable dengue vaccine. Currently, attention is focused on the development of either live attenuated vaccines or live attenuated chimaeric vaccines using a variety of backbones. Alternate vaccine approaches, such as whole inactivated virus and subunit vaccines are in the early stages of development, and are each associated with different problems. Subunit vaccines offer the advantage of providing a uniform antigen of well-defined nature, without the added risk of introducing any genetic material into the person being inoculated. Preliminary trials of subunit vaccines (using dengue E protein) in rhesus monkeys have shown promising results. However, the primary disadvantages of dengue subunit vaccines are the low levels of expression of dengue proteins in mammalian or insect cells, as well as the added unknown risks of antigens produced from mammalian cells containing other potential sources of contamination. In the past two decades, plants have emerged as an alternative platform for expression of biopharmaceutical products, including antigens of bacterial, fungal or viral origin. In the present minireview, we highlight the current plant expression technologies used for expression of biopharmaceutical products, with an emphasis on plants as a production system for dengue subunit vaccines.

Production of complex viral glycoproteins in plants as vaccine immunogens

“…These concerns have been further compounded by the finding that infection with ZIKV during pregnancy was associated with birth defects during a recent outbreak in Brazil (Yakob and Walker, 2016). Similar limitations in terms of the scalability and production costs of conventional production platforms as for influenza vaccines have driven interest in the potential of molecular farming to produce vaccines for these emerging flaviruses (Cardona-Ospina et al, 2016;He et al, 2014;Yap and Smith, 2010). Several dengue envelope antigens have been produced in plants, although there is a paucity of immunogenicity data to support their utility as vaccine immunogens (Kim et al, 2010(Kim et al, , 2012Martinez et al, 2010;Saejung et al, 2007).…”

The development of recombinant subunit envelope-based vaccines to protect against dengue virus induced disease

“…In an effort to express recombinant E proteins several different expression systems have been utilized, including Escherichia coli , baculovirus vectors, yeast, mammalian cells, insect cells and more recently plant based expression systems (recently reviewed in ref. 27 and 28 and summarized in Table 1). Proper folding of the envelope protein is required to preserve the integrity of its neutralizing epitopes and this generally requires the coexpression of the premembrane (prM) protein along with E [29].…”

Overview of Plant-Derived Vaccine Antigens: Dengue Virus

“…Despite decades of efforts, no licensed vaccine for dengue disease is currently available on the world market (84,113,114). Vaccine development would be a major concern because dengue virus infections have led to the death of many people and now it is a major economic issue, especially in developing countries (84,114,115). The development of a dengue virus vaccine is difficult, because every serotype provides life-long immunity, but infection with a heterologus virus enhances the disease severity (113,114,115).…”

“…Vaccine development would be a major concern because dengue virus infections have led to the death of many people and now it is a major economic issue, especially in developing countries (84,114,115). The development of a dengue virus vaccine is difficult, because every serotype provides life-long immunity, but infection with a heterologus virus enhances the disease severity (113,114,115). This phenomenon is called antibody-dependent enhancement (ADE), and occurs often in children born to dengue-immune mothers (114).…”