Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines

Criscuolo, E.; Caputo, V.; Diotti, R. A.; Sautto, G. A.; Kirchenbaum, G. A.; Clementi, N.

Unfortunately, there are some disadvantages undermining their applications. First, plastids are not suitable for production of antigens that require glycosylation for proper folding or those antigens in which a protective immune response requires glycan recognition. However, nuclear transformation represents a valid option. Secondly, antigen expression can be either transient or stable in plants, but the second is preferred in order to obtain a stable genetic resource. In fact, transgenic seeds represent a constant resource to grow the transgenic plants and to extract proteins. However, stable transformation is time-consuming [25] . Moreover, expression in stable transformed crop plants suffers from low yields, typically less than 1% of TSP [36] . On the other hand, transient expression technology using either Agrobacterium or viral vectors is robust, quick, and easy to manipulate [37] . However, this expression is typically unstable [30] . Another important challenge of plant-based oral vaccines is the lack of a proper dosing strategy because low doses may not be able to induce a sufficient immune response and high doses, as previously described, may lead to immune tolerance. To this end, freeze-drying methods were implemented to stabilize plant biomass, concentrate the antigen, and achieve an accurate dosage by quantifying the antigen in terms of dry biomass weight, as mentioned above [31, 38] .