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

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

Apart from controlling particle size to achieve specific targeting passively, inclusion of targeting ligand could also increase uptake by M cells [133, 137] . A number of pathogens including reovirus [138] , Salmonella typhimurium [139] and Mycobacterium tuberculosis [140] target M cells as a mode of entry into the host. By identifying the key molecules expressed by these pathogens that are crucial for their invasion, it would be extremely helpful to design an effective delivery system for M cells targeting [141] . One example is related to reoviruses which target M cells using their surface protein sigma-1 (σ1). In this regard, Wu et al. reported an M cell targeting DNA vaccine delivery system consisting plasmid DNA and the recombinant protein σ1 as targeting ligand which was covalently attached to poly-L-lysine (PLL) for intranasal vaccination in mice. The results showed significant mucosal sIgA production as well as enhanced cell-mediated immunity [65] . Other ligands such as Co-1 peptide [142] , Claudin 4 targeting peptide [134, 143] and M cell specific monoclonal antibody (NKM 16-2-4) [144] have been investigated for M cell targeting in mucosal protein vaccine, with the potential to be explored for mucosal DNA vaccine delivery. However, mucosally induced tolerance may develop with M cell targeting delivery system. Following nasal administration of protein σ1 genetically conjugated with ovalbumin, systemic unresponsiveness was induced instead of mucosal IgA immunity [145] . Therefore, special attention must be paid with the development of M cell targeting delivery system.