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.

To date, the most well-studied vaccine delivery platforms capable of eliciting both mucosal and systemic immunities are edible or intradermal vaccine formulations ( Figure 1 ). Oral vaccines stimulate the generation of immunity in gut-associated lymphoid tissue (GALT), which includes lymph nodes, Peyer's patches (in which lymphocytes are the major component:~75% are B cells, while~20% are T cells), and isolated lymphoid follicles in the gastrointestinal tract (GIT). An effective immunization using oral vaccines is achieved when sufficient quantities of antigen are transported across the mucosal barrier by M cells into Peyer's patches and subsequently presented to T cells by antigenpresenting cells (APCs) [11] . Briefly, professional APCs display peptide fragments of the antigen in the context of the major histocompatibility complex (MHC) on their surface, which leads to activation of CD4 + T cells [12] . Subsequently, activated CD4 + T cells support germinal center development, including B cell affinity maturation and class switching to IgA, through providing CD40/CD40 ligand interactions and cytokine secretion [13] [14] [15] . Moreover, through the expression of specific chemokine homing receptors (e.g., CXCR5 or CCR10), antigen-experienced B cells migrate to distant effector regions where they differentiate into plasma cells capable of secreting dimeric or polymeric Figure 1 : Alternative methods of vaccine delivery. Development of rationally designed vaccines starts with the identification of the gene encoding for the protective antigenic protein(s). Subsequently, the antigen(s) can be incorporated into different edible systems, as plants, algae, insects, or yeasts, or used for intradermal formulations to induce a mucosal protective response. Following the administration of the edible vaccine and the subsequent passage of the antigen(s) through the M cell compartment delivering it to dendritic cells, the individual's immune system triggers a response leading also to specific IgA production and secretion. Similarly, patches with coated microprojections or biodegradable needles activate Langerhans cells and dermal dendritic cells in the skin dermis. These cells capture and present the antigen(s) to T and B lymphocytes, triggering both a mucosal and a systemic immunity.