Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

Xu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-Wing

It is well established that mucosal vaccination can induce humoral and cell-mediated immune response systemically as well as at mucosal sites [56, 57] . Immune response induced by mucosal vaccination is mainly initiated at specific mucosa-associated lymphoid tissue (MALT). The MALT lining the nasal cavity is known as the nasopharyngeal-associated lymphoid tissue (NALT), which include the Waldeyer's ring of tonsils, adenoids and a collection of isolated subepithelial lymphoid follicles [63] . The NALT is rich in immunocompetent cells, including B cells, T cells and phagocytic APCs such as macrophages and DCs [64] . In addition, the overlying epithelium of mucosal follicles forms a specialized cell layer. These cells have microfolds on their apical surface and are known as microfold cells (M cells). M cells play a crucial role in the initial phase of induction of mucosal immune responses. Therefore, M cell targeting is an important strategy to achieve mucosal immunity [65, 66] . M cells are efficient in taking up particles from the epithelial surface, transporting them across the cells and releasing them to the underlying extracellular space. This process is known as transcytosis. At their basal surface, the cell membrane of M cells is extensively folded around the underlying immune cells including B cells, T cells and APCs, which take up the particles released from M cells and process them for antigen presentation. The initiation of mucosal immune response is summarized in Figure 2 . Upon B cells activation following nasal vaccination, the production of antigen-specific secretory immunoglobulin A (sIgA) is triggered. sIgA is a critical component in the mucosal immune system. It is protease resistant, and can effectively bind and neutralize pathogens and their toxic products on the nasal mucosa surface despite the protease rich environment, thereby preventing the pathogens from breaching the mucosal barrier [67] . Local immunoglobulin G (IgG) production is also detected after mucosal vaccination [68] and partly contributes to the neutralization of pathogens. However, IgG concentration is around 30-100-fold lower than that of the sIgA due to its susceptibility to protease degradation [56] . Indeed, sIgA provides the first barrier to pathogens invasion, so induction of potent sIgA response is an important goal of mucosal vaccination. In addition, nasal immunization can also result in the production of serum IgA and serum IgG, which can potentially neutralize pathogens that enter the mucosa and prevent systemic spread. When the DCs at the mucosa are presented with antigens, the activated cells may migrate to the proximal draining lymph node and disseminate immune responses to other sites of the body. Apart from the humoral immune response, cell-mediated immune response is also induced after mucosal vaccination. Although the cytotoxic T cells in the mucosal tissues may not prevent pathogen entry, they are crucial for the clearance of pathogens [56] .