The MucoRice-CTB vaccine protects against cholera and enterotoxigenic Escherichia coli (ETEC) - two serious diarrhoeal diseases prevalent in low-income countries - and was developed by researchers at the International Research Development Center for Mucosal Vaccines (IMSUT) in Japan.
The orally-administered vaccine has been made by introducing antisense genes specific for rice storage proteins that swap out the usual carbohydrates for the vaccine antigens, in this case cholera toxin B subunit (CTB). It is stable at room temperature and easy to bulk produce, according to Astellas.
While transgenic plants have been held up for years as a way to produce low-cost recombinant proteins such as vaccines and biologic drugs, to date progress has been patchy and there is as yet no approved plant-based vaccine on the market. However, in 2012 the US FDA did approve an enzyme replacement therapy - Protalix' Elelyso (taliglucerase alfa) - that is made in carrots.
Among the main obstacles to overcome with the approach is the variability that can be introduced by making them in plant-made systems, with characteristics changing depending on the age of the plant or the growing conditions, as well as the potential development of immuno-tolerance to the vaccine antigens.
IMSUT has been working to improve the process for making MucoRice-CTB for years, refining a hydroponics-based closed cultivation system that minimises variations in expression and quality during vaccine manufacture.
The production unit can operate all year round, generating three harvests of vaccine-laden rice plants per year. The rice is polished and powdered to release the MucoRice-CTB drug substance.
Astellas' decision to license MucoRice-CTB is an indication that transgenic plant production of vaccines is starting to become a commercial prospect. The Japanese firm has committed to conducting trials of the vaccine using clinical trial materials (CTM) produced by IMSUT, and will also work with the Institute on other vaccine candidates.
"In developing countries, diarrhoea caused by pathogenic bacteria such as Vibrio cholerae and ETEC, is one of the major causes of death among infants," said Astellas in a statement.
"At present, the challenges of the cholera vaccines used in developing countries are the need for the cold chain and the ineffectiveness against ETEC," it added.
In addition to being easier to transport and dose, plant-based vaccine systems do not harbour human or animal pathogens and are typically cheaper to produce than those made by traditional recombinant protein production techniques.
They also have advantages over injectable vaccines in that when dosed orally or intranasally they provide not only systemic but also local 'mucosal immunity', which protects mucous membrane surfaces in the body from invasion by pathogens.