Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

Abstract

In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens.

Figure 1. The last 5 years of publications of mucosal vaccines, adjuvants, and delivery systems by 2002 and 2009

In order to induce effective mucosal immunity, mucosal adjuvants or live-attenuated microbial delivery systems are required. Enterotoxin-based mucosal adjuvants are the most potent and well-established strategy for the induction of both mucosal and systemic immunity to coadministered protein antigens. However, studies in toxin-based mucosal adjuvants are decreasing and the efforts are now focusing more on alternative safe and effective vaccine development. CpG: Cytidine phosphoguanosine; ISCOM: Immune stimulating complex; VLP: Virus-like particle.

Figure 2. Dendritic cell-targeting Flt3 ligand-encoded plasmid as mucosal adjuvant

Nasal administration of pFL as mucosal adjuvant preferentially expands the numbers of nasopharyngeal-associated lymphoreticular tissue DCs for the induction of coadministered antigen-specific immune responses. CMI: Cell-mediated immunity; CpG-ODN: Cytidine phosphoguanosine oligodeoxynucleotide; DC: Dendritic cell; pDC: Plasmacytoid dendritic cell; pFL: Flt3 ligand-encoded plasmid; TLR: Toll-like receptor.

Figure 3. DNA-based double mucosal adjuvants induce antigen-specific secretory IgA antibody responses and cell-mediated immunity

Nasal application of Flt3 ligand-encoded plasmid and CpG oligodeoxynucleotide selectively target CD8⁺ dendritic cells (DCs) and plasmacytoid DCs (pDCs), respectively. Subsequently, CD8⁺ DCs induce Th2-type cytokine responses, whereas pDCs promote Th1-type cytokine production for the induction of antigen-specific secretory IgA antibody responses and cell-mediated immunity. B: B cell; NALT: Nasopharyngeal-associated lymphoreticular tissue; T: T cell; TM: Transmembrane.